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nomifensine

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Description

Nomifensine is a tetracyclic antidepressant with a chemical structure similar to the phenothiazines. It was synthesized in the 1960s and marketed in the 1970s as an antidepressant. Nomifensine acts as a dopamine reuptake inhibitor, and also has some affinity for serotonin and norepinephrine transporters. It was found to be effective in treating major depressive disorder, but its use was limited by side effects such as extrapyramidal symptoms and hepatotoxicity. Nomifensine has been investigated for its potential use in the treatment of other conditions, including Parkinson's disease and attention-deficit/hyperactivity disorder. However, further research is needed to determine its efficacy and safety in these conditions. Nomifensine is currently not available in the United States. It is still used in some European countries for the treatment of depression.'

Nomifensine: An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

nomifensine : An N-methylated tetrahydroisoquinoline carrying phenyl and amino substituents at positions C-4 and C-8, respectively. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID4528
CHEMBL ID273575
CHEBI ID116225
SCHEMBL ID49380
MeSH IDM0014947

Synonyms (119)

Synonym
BRD-A29644307-050-05-5
8-amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline
isoquinoline, 1,2,3,4-tetrahydro-8-amino-2-methyl-4-phenyl-
DIVK1C_000789
KBIO1_000789
24526-64-5
2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine
nomifensinum [inn-latin]
nomifensina [inn-spanish]
linamiphen
8-isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-
8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisochinolin
nomifensine [inn:ban]
ccris 9179
SPECTRUM_000899
BSPBIO_002565
PRESTWICK3_000108
IDI1_000789
PRESTWICK2_000108
BPBIO1_000106
SPECTRUM5_001004
LOPAC0_000875
BSPBIO_000096
2-methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine 2-butenedioate
2-methyl-4-phenyl-3,4-dihydro-1h-isoquinolin-8-amine
nomifensine maleate(usan)
AB00053664
nomifensine
d,l-nomifensine
DB04821
(+-)-nomifensine
(+-)-nomifensin
nomifensin
2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
KBIOGR_001438
KBIO2_003947
KBIO2_001379
KBIO3_001785
KBIOSS_001379
KBIO2_006515
SPECTRUM4_001079
PRESTWICK0_000108
SPECTRUM2_001548
SPBIO_001396
SPECTRUM3_000963
NINDS_000789
SPBIO_002035
PRESTWICK1_000108
NCGC00089794-02
r/s-nomifensine
CHEBI:116225 ,
nomiphensine
nomifensina
nomifensinum
nomifenison
NCGC00015727-06
L001242
CHEMBL273575 ,
FT-0654152
2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine(nomifensine)
nomifensine2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine (nomifensine)
bdbm50005548
(+/-)-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
(+)-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
(-)-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
(nomifensine) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine
NCGC00255316-01
dtxsid0023377 ,
dtxcid803377
tox21_301755
cas-24526-64-5
CCG-204957
AKOS015919487
NCGC00015727-04
NCGC00015727-03
NCGC00015727-07
1lgs5jrp31 ,
hsdb 7702
unii-1lgs5jrp31
2-methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine
8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline
FT-0673030
gtpl4792
(+/-)-nomifensine
nomifensine [mi]
isoquinoline, 8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-
2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine
(+/-)-nomifensin
1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine
nomifensine [inn]
nomifensine [hsdb]
nomifensine [who-dd]
SCHEMBL49380
8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline
CS-4708
mfcd00242716
HY-B1110
AC-31222
AB00053664_13
AB00053664_14
J-015551
SBI-0050850.P003
Q409948
118184-50-2
((c)i)-nomifensin b(z)-4-hydroxy-4-oxo-but-2-enoate
BCP13731
BRD-A29644307-050-10-5
SDCCGSBI-0050850.P004
NCGC00015727-15
(+/-)-nomifensine maleat
()-nomifensine maleat
( inverted exclamation marka)-nomifensin
A877886
2-methyl-4-phenyl-1,2,3,4-tetrahydroquinolin-8-amine
BS-22102
2-methyl-4-phenyl-1 pound not2 pound not3 pound not4-tetrahydroisoquinolin-8-amine
EN300-7376971
Z2216900850

Research Excerpts

Overview

Nomifensine is an antidepressant agent that was removed from use because of a high incidence of hemolytic anemia. It is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or recently introduced agents.

ExcerptReferenceRelevance
"Nomifensine is a dopamine/norepinephrine reuptake inhibitor. "( Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice.
Asano, H; Chatani, R; Hall, FS; Hayata, S; Kitanaka, J; Kitanaka, N; Nishiyama, N; Takemura, M; Tanaka, KI; Uhl, GR; Yokoyama, H, 2012
)
2.16
"Nomifensine is an antidepressant agent that was removed from use because of a high incidence of hemolytic anemia. "( Metabolism of nomifensine to a dihydroisoquinolinium ion metabolite by human myeloperoxidase, hemoglobin, monoamine oxidase A, and cytochrome P450 enzymes.
Dalvie, DK; Obach, RS, 2006
)
2.14
"Nomifensine is an isoquinoline antidepressant that inhibits the reuptake of dopamine at central synapses. "( Nomifensine maleate (Merital, Hoechst-Roussel).
Fields, ED,
)
3.02
"Nomifensine is a tetrahydoisoquinoline antidepressant which is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or the recently introduced agents. "( Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness.
Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1979
)
3.15
"1. Nomifensine is a new antidepressant of novel chemical structure (a tetrahydroisoquinoline) with a pharmacological and therapeutic profile which differentiates it from any existing group of psychotropic agents. "( A profile of nomifensine.
Hanks, GW, 1977
)
1.25
"1. Nomifensine is a new substance which showed, in tests for antidepressant activity, a pronounced effect which is quantitatively better than that of the reference substances. "( A comparative review of the pharmacology of nomifensine.
Hoffmann, I, 1977
)
1.14
"11C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo."( In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography.
Antoni, G; Aquilonius, SM; Bergström, K; Eckernäs, SA; Gee, A; Hartvig, P; Leenders, KL; Lundquist, H; Rimland, A; Uhlin, J, 1987
)
0.99
"11C-nomifensine seems to be a valuable tool for investigating noradrenergic and dopaminergic re-uptake sites in vivo."( Monoamine re-uptake sites in the human brain evaluated in vivo by means of 11C-nomifensine and positron emission tomography: the effects of age and Parkinson's disease.
Aquilonius, SM; Gee, AG; Hartvig, P; Långström, B; Lundqvist, H; Tedroff, J; Uhlin, J, 1988
)
0.98
"Nomifensine is a widely used antidepressant agent with few side-effects but haemolytic anaemia with acute renal failure has been reported with both intermittent therapeutic dosage and self-inflicted overdose. "( Intravascular haemolysis and acute renal failure induced by nomifensine.
Briggs, JD; Dominiczak, AF; Fulton, JD; Junor, BJ; Lucie, NP, 1986
)
1.96
"Nomifensine is a potent noradrenergic and dopaminergic agent with low anticholinergic activity, and minimum cardiotoxicity and low morbidity/mortality in overdose."( Second generation antidepressants: a comparative review.
Coccaro, EF; Siever, LJ,
)
0.85
"Nomifensine is a potent inhibitor of norepinephrine but has little effect on serotonin."( Nomifensine maleate: a new second-generation antidepressant.
Kinney, JL,
)
2.3
"Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. "( The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia.
Mueller-Eckhardt, C; Salama, A, 1985
)
1.97

Effects

Nomifensine has been proposed as a dynamic test to discriminate tumoral from functional hyperprolactinaemia. It has no inhibitory effect in vitro on platelet MAO activity in depressed schizophrenic pellets.

ExcerptReferenceRelevance
"Nomifensine has a very short t1/2 and no tendency for accumulation after repeated doses."( Metabolism of nomifensine after oral and intravenous administration.
Lindberg, RL; Syvälahti, EK, 1986
)
1.35
"Nomifensine has demonstrated efficacy in several animal models that have been found to be predictive of clinical antidepressant activity, and has also been found to have a low potential for both cardiovascular and anticholinergic side effects. "( Pharmacology of nomifensine: a review of animal studies.
Fielding, S; Szewczak, MR, 1984
)
2.06
"Nomifensine has recently been proposed as a dynamic test to discriminate tumoral from functional hyperprolactinaemia. "( Some critical considerations on the use of the nomifensine test in the hyperprolactinaemic syndrome.
Aliffi, A; D'Agata, R; Gulizia, S; Mongioì, A; Vicari, E; Volpicelli, D, 1981
)
1.96
"Nomifensine also has antianxiety activity, but its role in treating anxiety associated with primary depression has still to be clarified."( Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness.
Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1979
)
2.42
"2. Nomifensine has no inhibitory effect in vitro on platelet MAO activity in depressed schizophrenic pellets."( Effect of nomifensine on platelet monoamine oxidase activity in chronic schizophrenic patients.
Filinger, EJ, 1989
)
1.19
"Nomifensine has been incriminated in causing immune hemolysis in a large number of patients."( On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia.
Mueller-Eckhardt, C; Salama, A, 1987
)
0.99
"Nomifensine has a very short t1/2 and no tendency for accumulation after repeated doses."( Metabolism of nomifensine after oral and intravenous administration.
Lindberg, RL; Syvälahti, EK, 1986
)
1.35

Actions

Nomifensine failed to suppress the serum PRL in all subjects. PRL responses to TRH and insulin-induced hypoglycemia were impaired in all patients, irrespective of the origin of hyperprolactinemia. Nomifensin was found to inhibit the extracellular uptake of NE in rat cerebeller cortex similar to ethanol.

ExcerptReferenceRelevance
"Nomifensine failed to suppress the serum PRL in all subjects and PRL responses to TRH and insulin-induced hypoglycemia were impaired in all patients, irrespective of the origin of hyperprolactinemia."( Nomifensine, TRH and insulin-induced hypoglycemia tests in the diagnosis of prolactinomas.
Fachinetti, A; Fachinetti, P; Iannotta, F; Pinotti, G; Usellini, L, 1983
)
2.43
"Nomifensine was found to inhibit the extracellular uptake of NE in rat cerebeller cortex similar to ethanol."( Ethanol inhibits the uptake of exogenous norepinephrine from the extracellular space of the rat cerebellum.
Bickford, PC; Gerhardt, GA; Lin, AM; Palmer, MR, 1993
)
1.01
"3. Nomifensine does not inhibit MAO and does not enhance the release of biogenic amines."( Studies on brain metabolism of biogenic amines.
Bäcker, G; Leven, M; Schacht, U, 1977
)
0.77
"The nomifensine-induced increase in dopamine (202 +/- 23% of basal) was similar to that of methylphenidate, whereas the increase in neurotensin was significantly delayed and of lower magnitude (134 +/- 20% of basal)."( Effects of CNS stimulants on the in vivo release of the colocalized transmitters, dopamine and neurotensin, from rat prefrontal cortex.
Bean, AJ; During, MJ; Roth, RH, 1992
)
0.76
"Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients."( Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia.
Ibayashi, H; Ikuyama, S; Karashima, T; Kato, K; Muta, K; Sekiya, K, 1985
)
0.99

Treatment

Nomifensine likely treated depression by acting on dopamine, norepinephrine and 5-HT neurons. The nomifensin-treated depressed patients showed significant improvement over the placebo depressed patients early in and throughout treatment. Nom ifensine did not influence salivary flow and did not significantly affect psychomotor performance.

ExcerptReferenceRelevance
"Nomifensine likely treated depression by acting on dopamine, norepinephrine and 5-HT neurons, highlighting the importance of the functional connectivity between these three monoaminergic systems."( Effects of acute and sustained administration of the catecholamine reuptake inhibitor nomifensine on the firing activity of monoaminergic neurons.
Blier, P; El Mansari, M; Guiard, BP; Katz, NS, 2010
)
1.31
"The nomifensine-treated depressed patients showed significant improvement over the placebo depressed patients early in and throughout treatment."( Nomifensine in geriatric inpatients: a placebo-controlled study.
Jansen, W; Siegfried, K, 1984
)
2.19
"2 Nomifensine treatment did not influence salivary flow and did not significantly affect psychomotor performance (critical flicker fusion, pursuit rotor and reaction time): in addition nomifensine had no significant effect on subjective measurements of sedation and concentration."( A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.
Chan, MY; Ehsanullah, R; McEwen, J; Wadsworth, J, 1980
)
1.07
"Nomifensine treatment significantly increased TH enzyme amount in substantia nigra (39.2%), which was accompanied by a significant increase in TH enzyme activity (47.8%)."( Chronic inhibition of the high-affinity dopamine uptake system increases oxidative damage to proteins in the aged rat substantia nigra.
Cano, J; Machado, A; Rodríguez-Gómez, JA; Romero-Ramos, M; Venero, JL, 1997
)
1.02
"Nomifensine pretreatment induced no changes in the in vivo binding indexes of the high affinity [125I]NCQ298 and a slight but not significant decrease of the binding indexes of 125I]iodolisuride."( Effects of dopamine on the in vivo binding of dopamine D2 receptor radioligands in rat striatum.
Fazio, F; Guibert, B; Leviel, V; Loc'h, C; Maziere, B; Maziere, M; Moresco, RM; Ottaviani, M, 1999
)
1.02
"Nomifensine treatment group had fewer side effect, whereas the Imipramine group had more adverse experiences."( [A double-blind comparison study of nomifensine and imipramine in treating depressed patients].
Wang, XJ, 1989
)
1.27
"Treatment with nomifensine alone (3 mg/kg) also induced dyskinesias."( Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa.
Di Monte, DA; Langston, JW; Protell, P; Quik, M; Tan, LC; Togasaki, DM, 2005
)
0.92
"Pretreatment with nomifensine attenuated the depletion of striatal dopamine induced by intrastriatal injections of 6-hydroxydopamine, consistent with inhibition of dopamine uptake in vivo."( Effects of nomifensine and desipramine on the sequelae of intracerebrally-injected 6-OHDA and 5,6-DHT.
Waddington, JL, 1980
)
0.97
"Treatment with nomifensine or dopamine/nomifensine increased the recovery of dopamine in the effluent samples as compared to treatment with dopamine alone."( Use of in vitro superfusion to assess the dynamics of striatal dopamine clearance: influence of estrogen.
Disshon, KA; Dluzen, DE, 1999
)
0.64
"Pretreatment with nomifensine, an inhibitor of DA reuptake, was also without effect on the surge, but reduced the rate of DA decline after reperfusion to one-fifth of the rate without the pretreatment."( Effects of transient forebrain ischemia and reperfusion on function of dopaminergic neurons and dopamine reuptake in vivo in rat striatum.
Akiyama, Y; Ito, A; Kikuchi, H; Koshimura, K; Miwa, S; Ohue, T; Yamagata, S, 1991
)
0.6
"Pretreatment with nomifensine (25 mg/kg, intraperitoneally) prevented the decrease in DA only in the striatum."( Acute electrophysiological and neurochemical effects of administration of MPTP in mice.
Jonsson, G; Schultz, W; Studer, A; Sundström, E, 1988
)
0.6

Toxicity

Nomifensine appeared safe and superior to placebo on several key measures of depressive symptomatology in this multicenter study of depressed outpatients.

ExcerptReferenceRelevance
" LD50 values of three of these compounds were assessed after intraperitoneal administration with a special emphasis on interactions with drugs increasing catecholaminergic neurotransmission."( Acute toxicity of three new selective COMT inhibitors in mice with special emphasis on interactions with drugs increasing catecholaminergic neurotransmission.
Männistö, PT; Törnwall, M, 1991
)
0.28
"Drug-induced hematological disorders appear as a rare but serious side effect of the drugs use."( [Hematologic toxicity of antidepressive agents].
Galbaud du Fort, G,
)
0.13
" The results are compatible with the view that the monoamine oxidase-catalyzed conversion of MPTP to a toxic metabolite MPP+ occurs mainly extraneuronally."( Differential time course of protection by monoamine oxidase inhibition and uptake inhibition against MPTP neurotoxicity on central catecholamine neurons in mice.
Jonsson, G; Sundström, E, 1986
)
0.27
" The findings indicate that MPTP (or MPP+) is a substrate for the specific DA reuptake system and may explain, in part, its selective toxic effects on DA neurons."( Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP.
Cohen, O; Globus, M; Melamed, E; Rosenthal, J; Uzzan, A, 1985
)
0.27
" Nomifensine thus appeared safe and superior to placebo on several key measures of depressive symptomatology in this multicenter study of depressed outpatients."( Double-blind placebo-controlled multicenter evaluation of the efficacy and safety of nomifensine in depressed outpatients.
Brauzer, B; Charalampous, KD; Goldstein, BJ; Kentsmith, D; Rosenthal, S, 1984
)
1.4
" The proportions of patients experiencing at least one side effect or dropping out due to side effects were almost twice as high in the imipramine group."( Multicenter double-blind comparison of nomifensine and imipramine for efficacy and safety in depressed outpatients.
Abrahams, LM; Bremner, JD; Crupie, JE; McCawley, A; Proctor, RC; Sathananthan, GL, 1984
)
0.54
" The findings suggest a more favorable side effect profile for nomifensine, which was associated with a lower frequency of sedating and anticholinergic effects than was seen in the imipramine group."( A double-blind comparative evaluation of the efficacy and safety of nomifensine, imipramine, and placebo in depressed geriatric outpatients.
Feighner, JP; Hendrickson, G; Merideth, CH, 1984
)
0.74
" Side effects include sleep disturbance, restlessness, and nausea; rare adverse reactions are in keeping with other antidepressants."( A review of the clinical safety and tolerability of nomifensine.
Stonier, PD, 1984
)
0.52
" Side effect information was collected at each visit."( An overview of side effects and long-term experience with nomifensine from United States clinical trials.
Hardiman, S; Nash, RJ; Yakabow, AL, 1984
)
0.51
"Dopamine (DA), at concentrations greater than 100 microM, has previously been demonstrated to be toxic to mesencephalic, striatal and dorsal root ganglion cell cultures."( Dopamine neurotoxicity in cortical neurons.
Alagarsamy, S; Johnson, KM; Pappas, T; Phillips, M, 1997
)
0.3
" Our results suggest that dopamine causes primarily apoptotic death of striatal neurons in culture without damaging cells by an early adverse action on oxidative phosphorylation."( Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor.
Chesselet, MF; Erecińska, M; McLaughlin, BA; Nelson, D, 1998
)
0.3
" Tetrahydrobiopterin, an essential cofactor for tyrosine hydroxylase, may act as an antioxidant in dopaminergic neurones and protects against the toxic consequences of glutathione depletion."( Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures.
Gramsbergen, JB; Hesslinger, C; Jansen, P; Madsen, JT; Meyer, M; Zimmer, J, 2003
)
0.32
" No toxic effects in RCSN-3 cells were observed when the cells were incubated with 100 microm FeCl3 alone or complexed with dopamine."( Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra.
Cardenas, S; Caviedes, P; Graumann, R; Martinez-Alvarado, P; Olea-Azar, C; Paris, I; Perez-Pastene, C; Raisman-Vozari, R; Segura-Aguilar, J; Vieira, MN, 2005
)
0.33
" All of these effects of ATR were observed at levels that were not toxic to the tissue, as LDH release into the medium (lactate dehydrogenase, an index of non-specific cytotoxicity) was not affected by ATR."( Dopaminergic toxicity of the herbicide atrazine in rat striatal slices.
Carr, RL; Filipov, NM; Sistrunk, SC; Stewart, MA, 2007
)
0.34
" It is known that dopamine (DA) enhances this toxic effect."( Endogenous dopamine enhances the neurotoxicity of 3-nitropropionic acid in the striatum through the increase of mitochondrial respiratory inhibition and free radicals production.
Cano, J; de Pablos, RM; Herrera, AJ; Machado, A; Navarro, A; Santiago, M; Tomás-Camardiel, M; Villarán, RF, 2008
)
0.35
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."( Developing structure-activity relationships for the prediction of hepatotoxicity.
Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010
)
0.36
"Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites."( Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
Jones, LH; Nadanaciva, S; Rana, P; Will, Y, 2016
)
0.43

Pharmacokinetics

Nomifensine caused neither negative nor positive (euphoric) mood alterations and led to no impairments in various tests of performance. Six healthy male volunteers participated in a double-blind placebo crossover comparison of the pharmacodynamic profiles of single oral doses of 75 mg nom ifensine and 50 mg amitriptyline.

ExcerptReferenceRelevance
" After single doses the pharmacokinetic profile of clobazam includes time to peak levels 1--4 h after dosing, peak levels increasing linearly with the logarithm of dose, and terminal half-lives of about 18 hours."( Pharmacokinetics of single and multiple doses of clobazam in humans.
Badian, M; Bender, R; Christ, O; Hajdú, P; Kulkarni, RD; Rupp, W; Taeuber, K; Uihlein, M; Vanderbeke, O, 1979
)
0.26
" Plasma levels of nomifensine were examined using a radioimmunological determination method and pharmacokinetic parameters were calculated by computer program."( Pharmacokinetics of nomifensine in impaired renal function.
Heptner, W; Lameire, N; Munche, M; Ringoir, S; Taeuber, K, 1977
)
0.91
" Time-efficacy calculations showed the maximal pharmacodynamic effect of pirlindol in the 4th to 6th hour, of 75 mg imipramine in the 2nd hour, of 20 mg tranylcypromine in the 4th hour and of 150 mg nomifensine in the 6th hour."( [Classification and determination of the pharmacodynamics of a new tetracyclic antidepressive agent, pirlindol, using pharmaco-EEG and psychometry].
Grünberger, L; Linzmayer, L; Saletu, B; Stöhr, H; Wittek, R, 1983
)
0.45
"A review of pharmacodynamic studies of nomifensine in healthy subjects indicates that nomifensine caused neither negative nor positive (euphoric) mood alterations and led to no impairments in various tests of performance and to some improvement in vigilance, attention, and psychomotor performance."( Pharmacodynamics of nomifensine: a review of studies in healthy subjects.
Siegfried, K; Taeuber, K, 1984
)
0.86
" Nomifensine serum levels were determined by a radioimmunoassay; peak levels occurred within the first 2 h, the elimination half-life was around 2 h, both results indicating fast absorption and elimination."( The pharmacokinetics of nomifensine. Comparison of pharmacokinetics and pharmacodynamics using computer pharmaco-EEG.
Grünberger, J; Linzmayer, L; Saletu, B; Taeuber, K, 1982
)
1.48
"1 Six healthy male volunteers participated in a double-blind placebo crossover comparison of the pharmacodynamic profiles of single oral doses of 75 mg nomifensine and 50 mg amitriptyline."( A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.
Chan, MY; Ehsanullah, R; McEwen, J; Wadsworth, J, 1980
)
0.72
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35

Compound-Compound Interactions

We used brain microdialysis to study the effects of nicotine on extracellular levels of dopamine (DA) and its metabolites. The nicotinic agonists were given acutely and repeatedly either alone or in combination with a dopamine uptake inhibitor, nomifensine.

ExcerptReferenceRelevance
" The nicotinic agonists were given acutely and repeatedly either alone or in combination with a dopamine uptake inhibitor, nomifensine."( Comparison of the effects of nicotine and epibatidine given in combination with nomifensine on rotational behaviour in rats.
Ahtee, L; Janhunen, S; Tuominen, RK, 2005
)
0.76
" We used brain microdialysis to study the effects of nicotine on extracellular levels of dopamine (DA) and its metabolites in the rat dorsal striatum in combination with drugs inhibiting either DA uptake (nomifensine), catechol-O-methyltransferase (COMT; tolcapone), monoamine oxidase B (MAO-B; selegiline) or DA receptors (haloperidol)."( The effect of nicotine in combination with various dopaminergic drugs on nigrostriatal dopamine in rats.
Ahtee, L; Janhunen, S; Kaakkola, S; Mielikäinen, P; Paldánius, P; Tuominen, RK, 2005
)
0.52

Bioavailability

Two studies were conducted in normal male volunteers to establish the pharmacokinetic parameters for nomifensine maleate and to determine the bioavailability of the drug from the Merital capsule intended for U.S.

ExcerptReferenceRelevance
" Classical criteria for bioavailability (peak serum levels, time of peak, area under the serum level time curve) and the half-life of elimination from the serum were used for retrieval of pharmacokinetic information."( Kinetic interaction of nomifensine with a 1, 5-benzodiazepine (clobazam).
Bender, R; Heptner, W; Rupp, W; Taeuber, K; Uihlein, M, 1977
)
0.57
" This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects."( Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers.
Hietala, J; Lindberg, R; Pihlajamäki, K; Scheinin, H; Scheinin, M; Syvälahti, E, 1987
)
0.54
" The main reason for limited bioavailability seems to be extensive first-pass metabolism during the absorption process."( Disposition of nomifensine after acute and prolonged dosing.
Lindberg, RL; Pihlajamäki, KK; Syvälahti, EK, 1986
)
0.62
" The area under the serum concentration-time curve (AUC) obtained after oral administration was significantly smaller than that after intravenous administration indicating incomplete bioavailability of the drug in oral form."( First-pass metabolism of nomifensine in dogs.
Iisalo, E; Lindberg, R; Sellman, R,
)
0.43
" From cumulative excretions of nomifensine, complete relative bioavailability of a capsule formulation vs."( Quantitative thin-layer chromatography for routine determination of nomifensine and its metabolites in human urine.
Sistovaris, N, 1983
)
0.79
" Higher GH responsiveness to Nom is compatible with a different bioavailability of the drug."( Tubero-infundibular dopaminergic function in cirrhotic patients: evaluation by nomifensine and domperidone.
Cocchi, D; Lampertico, M; Locatelli, S; Monza, GC; Sali, L, 1983
)
0.49
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36

Dosage Studied

Nomifensine is a widely used antidepressant agent with few side-effects. haemolytic anaemia with acute renal failure has been reported with intermittent therapeutic dosage and self-inflicted overdose.

ExcerptRelevanceReference
" The dosage of nomifensine started at 50 mg, was increased to 150 mg daily, and other medication was continued unchanged."( Nomifensine in Parkinson's disease.
Bedard, P; Marsden, CD; Parkes, JD, 1977
)
2.05
" The dosage schedule was a flexible one, with a daily dose range from 50-200 mg for nomifensine and 50-225 mg for amitriptyline."( Dopaminergic agonist nomifensine compared with amitriptyline: a double-blind clinical trial in acute primary depressions.
Daigle, L; Grof, P; Mahutte, G; Saxena, B, 1977
)
0.8
" Dosage ranged from 50-225 mg daily, and treatment lasted from 2-26 weeks."( A review of controlled studies with nomifensine, performed outside the UK.
Habermann, W, 1977
)
0.53
" Daily dosage varied (50-225 mg), lenght of treatment also (226 weeks)."( [Nomifensine: clinical data (author's transl)].
Cayreyre, M; Clerc, G, 1978
)
1.17
" Drugs were administered according to a flexible dosage varying from 50 mg to 125 mg/day, subdivided in 2-3 doses."( [Controlled clinical trial of nomifensine in treatment of depression (author's transl)].
Ardito, P; Ferrara, M; Zaccara, G,
)
0.42
" Following each treatment the effect of tyramine was diminished, with a shift to the right in the tyramine dose-response curve."( Influence of nomifensine and desipramine on tyramine pressor responses in healthy volunteers.
McEwen, J, 1977
)
0.63
" It does not, therefore, have any therapeutic role in these conditions at the dosage used in this study."( Effects of nomifensine, an inhibitor of endogenous catecholamine re-uptake, in acromegaly, in hyperprolactinaemia, and against stimulated prolactin release in man.
Cook, DB; Dewar, JH; Evered, DC; Gomez-Pan, A; Hall, R; Hildyard, A; Mora, B; Scanlon, MF; Weightman, DR, 1977
)
0.65
" In the second experiment, neither d-amphetamine nor nomifensine altered the discriminative stimulus properties of ICSS, but a dose-response increase occurred in the time to complete the test session and in total number of lever presses and in presses on the initiating lever."( Effects of amphetamine and nomifensine on intracranial self-stimulation discrimination behavior in rats.
Michael, RP; Schaefer, GJ, 1992
)
0.83
" Experimental conditions provided several different doses of drug during each of two daily 130 min sessions; as a result, a dose-response curve relating rate of responding to dose/injection for self-administered drug was obtained within each session."( Drug-reinforced responding: rapid determination of dose-response functions.
Palmer, RK; Winger, G; Woods, JH, 1989
)
0.28
" In "endogenous" depression, a statistically significant linear dose-response relationship was found in all the efficacy variables assessed."( Therapeutic and side-effect profile of a selective and reversible MAO-A inhibitor, brofaromine. Results of dose-finding trials in depressed patients.
Delini-Stula, A; Heath, WR; Schiwy, W, 1989
)
0.28
" There were more withdrawals and dosage changes with nomifensine than with mianserin."( Depression and anxiety: mianserin and nomifensine compared in a double-blind multicentre trial.
Boscredon, J; Escande, M; Girard, M; Granier, F; Oules, J; Schmitt, L, 1985
)
0.79
" Pargyline in the dosage used is known to be a non-selective MAO inhibitor and it prevented the metabolism of 11C-MPTP to the products retained in the brain."( Influence of monoamine oxidase inhibitors and a dopamine uptake blocker on the distribution of 11C-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 11C-MPTP, in the head of the rhesus monkey.
Gullberg, P; Hartvig, P; Långström, B; Larsson, BS; Lindberg, BS; Lindquist, NG; Lundqvist, H; Malmborg, P; Oreland, L; Rimland, A, 1986
)
0.27
"Nomifensine is a widely used antidepressant agent with few side-effects but haemolytic anaemia with acute renal failure has been reported with both intermittent therapeutic dosage and self-inflicted overdose."( Intravascular haemolysis and acute renal failure induced by nomifensine.
Briggs, JD; Dominiczak, AF; Fulton, JD; Junor, BJ; Lucie, NP, 1986
)
1.96
" Two weeks of dosing had no significant influence on the elimination t1/2 or AUC values of the metabolites, indicating no change in the hydroxylation and methylation reactions."( Metabolism of nomifensine after oral and intravenous administration.
Lindberg, RL; Syvälahti, EK, 1986
)
0.63
" The effect of prolonged oral dosing on the pharmacokinetics of nomifensine was also evaluated."( Disposition of nomifensine after acute and prolonged dosing.
Lindberg, RL; Pihlajamäki, KK; Syvälahti, EK, 1986
)
0.86
" Prolonged treatment with nomifensin markedly reduced the response of the type I inhibitor both to low and high doses of apomorphine and shifted the dose-response curves to the right."( The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to apomorphine in rat striatum after prolonged treatment with nomifensin.
Szmigielska, H; Szmigielski, A; Zalewska, J,
)
0.13
" Twenty patients in each group received maprotiline or nomifensine over three weeks in the recommended daily dosage of 75 mg."( Incidence of cardiac arrhythmias during antidepressant therapy with maprotiline or nomifensine.
Bethge, KP; Blanco-Cruz, E; Godt, U; Lichtlen, PR,
)
0.6
" Its pharmaco-EEG profile, especially after higher dosage (150 and 225 mg), was characterized by a decrease in delta and theta activity, an increase in alpha activity and a delta and theta activity, an increase in alpha activity and a decrease in beta activity, as well as by an attenuation of the average frequency and frequency deviation and a trend towards an augmentation of the amplitude and amplitude variability."( [Classification and determination of the pharmacodynamics of a new tetracyclic antidepressive agent, pirlindol, using pharmaco-EEG and psychometry].
Grünberger, L; Linzmayer, L; Saletu, B; Stöhr, H; Wittek, R, 1983
)
0.27
" The dosage was 150 mg daily in both treatment groups."( Nomifensine and amitriptyline in the treatment of depression. A multi-centre double-blind comparison.
Agren, H; Bjaring, B; Källström, B; Lund, M; Månsby, J; Peterson, LE; Roos, BE; Wistedt, B, 1983
)
1.71
") was not inhibited at any dosage level in haloperidol-treated rats, and was enhanced by higher doses of nomifensine."( Enhancement of stereotypy induced by nomifensine in rats during continuous chronic haloperidol treatment.
Jenner, P; Marsden, CD; Rupniak, NM, 1984
)
0.75
" Dosage was 70-75 mg per diem."( [A controlled study on the effects of nomifensine treatment of depression in the elderly].
Allegro, L; Miotto, P; Ziliotto, G,
)
0.4
" The duration of treatment was 4 weeks and the dosage of both drugs ranged from 50 to 150 mg/day."( A double-blind clinical comparison between nomifensine and amitriptyline in the treatment of endogenous depressions.
Ayuso Gutierez, JL; López-Ibor Aliño, JJ; Montejo Iglesias, ML; Ramons, JL, 1982
)
0.53
" Administration of chlorimipramine in clinical dosage caused a complete disappearance of the 3H-mepyramine affinity for its receptor in the occipital cortex."( 3H-mepyramine binding in various regions of rat brain following chronic treatment with different classes of antidepressant drugs.
Dupont, A; Merand, Y; Savard, P, 1982
)
0.26
" The full dosage range of 50-200 mg/d is well tolerated, and doses can be selected to suit patient disease, age, and therapeutic response."( Nomifensine maleate (Merital, Hoechst-Roussel).
Fields, ED,
)
1.57
" The latter oral dosage could be discriminated from placebo only in certain variables at certain times."( The pharmacokinetics of nomifensine. Comparison of pharmacokinetics and pharmacodynamics using computer pharmaco-EEG.
Grünberger, J; Linzmayer, L; Saletu, B; Taeuber, K, 1982
)
0.57
" Although both compounds inhibited [3H]DA uptake with similar dose-response characteristics (IC50 approximately 300 microM and approximately 400 microM, respectively), the effect of NO was quicker in onset."( Inhibitory effects of nitric oxide on the uptake of [3H]dopamine and [3H]glutamate by striatal synaptosomes.
Johnson, KM; Lonart, G, 1994
)
0.29
" Animals also received four injections of nicotine to determine whether repetitive dosing leads to progressive reduction of the norepinephrine response."( Detection by in vivo microdialysis of nicotine-induced norepinephrine secretion from the hypothalamic paraventricular nucleus of freely moving rats: dose-dependency and desensitization.
Matta, SG; Sharp, BM, 1993
)
0.29
" Neuronal degeneration was observed in the substantia nigra pars compacta (SN), ventral tegmental area (VTA) and retrorubral field (RRF) of only animals dosed in the low temperature environment."( Systemic administration of MPTP induces thalamic neuronal degeneration in mice.
Ali, SF; Freyaldenhoven, TE; Schmued, LC, 1997
)
0.3
" In the present study, a K+ dose-response curve was obtained for the release of both [3H]-DA and endogenous DA from striatal tissue, in the absence and presence of catecholamine uptake blockers."( Mazindol, nomifensine and desmethylimipramine inhibit potassium-induced release of dopamine: effect of stimulus strength.
Dembiec-Cohen, D, 1998
)
0.7
" Dose-response curves were constructed for seven agonists in each of the brain regions."( Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain regions.
Cao, J; Collins, AC; Grady, SR; Marks, MJ; McIntosh, JM; Murphy, KL, 2002
)
0.31
"Animals were habituated overnight and dosed the next day, 5 h after lights on, with test agents."( The roles of dopamine transport inhibition and dopamine release facilitation in wake enhancement and rebound hypersomnolence induced by dopaminergic agents.
Bozyczko-Coyne, D; Gasior, M; Gruner, JA; Lin, YG; Marcy, VR; Marino, MJ, 2009
)
0.35
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."( FDA-approved drug labeling for the study of drug-induced liver injury.
Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011
)
0.37
" Hence, the successful development of future TRIs for depression will demand strong translational evidence, an optimal dosing regimen, and better tolerability."( Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges.
Subbaiah, MAM, 2018
)
0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
dopamine uptake inhibitorA dopaminergic agent that blocks the transport of dopamine into axon terminals or into storage vesicles within terminals. Most of the adrenergic uptake inhibitors also inhibit dopamine uptake.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
isoquinolinesA class of organic heteropolycyclic compound consisting of isoquinoline and its substitution derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (34)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
thioredoxin reductaseRattus norvegicus (Norway rat)Potency0.56230.100020.879379.4328AID588453
ATAD5 protein, partialHomo sapiens (human)Potency0.07300.004110.890331.5287AID493106
GLS proteinHomo sapiens (human)Potency12.58930.35487.935539.8107AID624146
GLI family zinc finger 3Homo sapiens (human)Potency26.85370.000714.592883.7951AID1259369; AID1259392
regulator of G-protein signaling 4Homo sapiens (human)Potency6.69520.531815.435837.6858AID504845
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency54.48270.003041.611522,387.1992AID1159552; AID1159555
pregnane X nuclear receptorHomo sapiens (human)Potency27.30600.005428.02631,258.9301AID1346982
ParkinHomo sapiens (human)Potency9.20000.819914.830644.6684AID720573
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency14.12540.035520.977089.1251AID504332
hexokinase-4 isoform 1Homo sapiens (human)Potency12.58932.511913.800328.1838AID743205
atrial natriuretic peptide receptor 1 precursorHomo sapiens (human)Potency8.49210.134610.395030.1313AID1347049
chromobox protein homolog 1Homo sapiens (human)Potency0.00530.006026.168889.1251AID488953
thyroid hormone receptor beta isoform 2Rattus norvegicus (Norway rat)Potency51.52020.000323.4451159.6830AID743065; AID743067
glucokinase regulatory proteinHomo sapiens (human)Potency12.58932.511913.800328.1838AID743205
tumor susceptibility gene 101 proteinHomo sapiens (human)Potency35.48130.129810.833132.6090AID485342
Ataxin-2Homo sapiens (human)Potency17.78280.011912.222168.7989AID588378
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Bile salt export pumpRattus norvegicus (Norway rat)IC50 (µMol)1,000.00000.40002.75008.6000AID1209456
Bile salt export pumpHomo sapiens (human)IC50 (µMol)1,000.00000.11007.190310.0000AID1209455; AID1449628
Cytochrome P450 2D6Homo sapiens (human)IC50 (µMol)20.00000.00002.015110.0000AID727360
DRattus norvegicus (Norway rat)IC50 (µMol)2.72400.00030.50267.7625AID179927; AID63031
D(3) dopamine receptorRattus norvegicus (Norway rat)IC50 (µMol)2.72400.00030.39075.4000AID179927; AID63031
Sodium-dependent noradrenaline transporter Homo sapiens (human)IC50 (µMol)0.63100.00081.541620.0000AID752492
Sodium-dependent noradrenaline transporter Homo sapiens (human)Ki0.02870.00031.465610.0000AID1388099; AID717270; AID727358; AID752492
Sodium-dependent dopamine transporterRattus norvegicus (Norway rat)IC50 (µMol)0.16420.00070.97749.7000AID65016; AID65018; AID65019; AID65020; AID65022; AID65023
Sodium-dependent dopamine transporterRattus norvegicus (Norway rat)Ki0.03430.00030.37088.1600AID65638; AID727216
D(1B) dopamine receptorRattus norvegicus (Norway rat)IC50 (µMol)2.72400.00030.35635.4000AID179927; AID63031
5-hydroxytryptamine receptor 1BRattus norvegicus (Norway rat)Ki0.02600.00031.29679.2440AID727216
D(4) dopamine receptorRattus norvegicus (Norway rat)IC50 (µMol)2.72400.00030.38715.4000AID179927; AID63031
Sodium-dependent serotonin transporterHomo sapiens (human)IC50 (µMol)8.70960.00010.86458.7096AID752491
Sodium-dependent serotonin transporterHomo sapiens (human)Ki1.56520.00000.70488.1930AID1388098; AID717268; AID727355; AID752491
Sodium-dependent serotonin transporterRattus norvegicus (Norway rat)IC50 (µMol)3.11500.00030.81978.4900AID179927; AID3654
Cytochrome P450 2C19Homo sapiens (human)IC50 (µMol)0.03160.00002.398310.0000AID611193
D(2) dopamine receptorRattus norvegicus (Norway rat)IC50 (µMol)2.72400.00010.54948.4000AID179927; AID63031
Sodium-dependent dopamine transporter Homo sapiens (human)IC50 (µMol)0.07810.00071.841946.0000AID1465046; AID550778; AID578421; AID611193; AID752493
Sodium-dependent dopamine transporter Homo sapiens (human)Ki0.06110.00021.11158.0280AID1388100; AID338161; AID717269; AID727357; AID752493
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)27.00000.00091.901410.0000AID727356
TransporterRattus norvegicus (Norway rat)Ki0.01200.00010.76295.5000AID717267; AID727217
TransporterRattus norvegicus (Norway rat)IC50 (µMol)2.70330.00081.95628.8000AID147592; AID179927
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (122)

Processvia Protein(s)Taxonomy
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processCytochrome P450 2D6Homo sapiens (human)
steroid metabolic processCytochrome P450 2D6Homo sapiens (human)
cholesterol metabolic processCytochrome P450 2D6Homo sapiens (human)
estrogen metabolic processCytochrome P450 2D6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid catabolic processCytochrome P450 2D6Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2D6Homo sapiens (human)
isoquinoline alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2D6Homo sapiens (human)
retinol metabolic processCytochrome P450 2D6Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 2D6Homo sapiens (human)
negative regulation of bindingCytochrome P450 2D6Homo sapiens (human)
oxidative demethylationCytochrome P450 2D6Homo sapiens (human)
negative regulation of cellular organofluorine metabolic processCytochrome P450 2D6Homo sapiens (human)
arachidonic acid metabolic processCytochrome P450 2D6Homo sapiens (human)
monoamine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent noradrenaline transporter Homo sapiens (human)
chemical synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent noradrenaline transporter Homo sapiens (human)
response to painSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent noradrenaline transporter Homo sapiens (human)
neuron cellular homeostasisSodium-dependent noradrenaline transporter Homo sapiens (human)
amino acid transportSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transportSodium-dependent serotonin transporterHomo sapiens (human)
response to hypoxiaSodium-dependent serotonin transporterHomo sapiens (human)
neurotransmitter transportSodium-dependent serotonin transporterHomo sapiens (human)
response to nutrientSodium-dependent serotonin transporterHomo sapiens (human)
memorySodium-dependent serotonin transporterHomo sapiens (human)
circadian rhythmSodium-dependent serotonin transporterHomo sapiens (human)
response to xenobiotic stimulusSodium-dependent serotonin transporterHomo sapiens (human)
response to toxic substanceSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of gene expressionSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of serotonin secretionSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of cerebellar granule cell precursor proliferationSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of synaptic transmission, dopaminergicSodium-dependent serotonin transporterHomo sapiens (human)
response to estradiolSodium-dependent serotonin transporterHomo sapiens (human)
social behaviorSodium-dependent serotonin transporterHomo sapiens (human)
vasoconstrictionSodium-dependent serotonin transporterHomo sapiens (human)
sperm ejaculationSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of neuron differentiationSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of cell cycleSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of organ growthSodium-dependent serotonin transporterHomo sapiens (human)
behavioral response to cocaineSodium-dependent serotonin transporterHomo sapiens (human)
enteric nervous system developmentSodium-dependent serotonin transporterHomo sapiens (human)
brain morphogenesisSodium-dependent serotonin transporterHomo sapiens (human)
serotonin uptakeSodium-dependent serotonin transporterHomo sapiens (human)
membrane depolarizationSodium-dependent serotonin transporterHomo sapiens (human)
platelet aggregationSodium-dependent serotonin transporterHomo sapiens (human)
cellular response to retinoic acidSodium-dependent serotonin transporterHomo sapiens (human)
cellular response to cGMPSodium-dependent serotonin transporterHomo sapiens (human)
regulation of thalamus sizeSodium-dependent serotonin transporterHomo sapiens (human)
conditioned place preferenceSodium-dependent serotonin transporterHomo sapiens (human)
sodium ion transmembrane transportSodium-dependent serotonin transporterHomo sapiens (human)
amino acid transportSodium-dependent serotonin transporterHomo sapiens (human)
long-chain fatty acid metabolic processCytochrome P450 2C19Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 2C19Homo sapiens (human)
steroid metabolic processCytochrome P450 2C19Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2C19Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 2C19Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2C19Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 2C19Homo sapiens (human)
monoamine transportSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent dopamine transporter Homo sapiens (human)
lactationSodium-dependent dopamine transporter Homo sapiens (human)
sensory perception of smellSodium-dependent dopamine transporter Homo sapiens (human)
locomotory behaviorSodium-dependent dopamine transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent dopamine transporter Homo sapiens (human)
response to iron ionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine transportSodium-dependent dopamine transporter Homo sapiens (human)
adenohypophysis developmentSodium-dependent dopamine transporter Homo sapiens (human)
response to nicotineSodium-dependent dopamine transporter Homo sapiens (human)
positive regulation of multicellular organism growthSodium-dependent dopamine transporter Homo sapiens (human)
regulation of dopamine metabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to cocaineSodium-dependent dopamine transporter Homo sapiens (human)
dopamine biosynthetic processSodium-dependent dopamine transporter Homo sapiens (human)
dopamine catabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to ethanolSodium-dependent dopamine transporter Homo sapiens (human)
cognitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent dopamine transporter Homo sapiens (human)
response to cAMPSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
prepulse inhibitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
hyaloid vascular plexus regressionSodium-dependent dopamine transporter Homo sapiens (human)
amino acid transportSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine transportSodium-dependent dopamine transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent dopamine transporter Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of receptor internalizationAtaxin-2Homo sapiens (human)
regulation of translationAtaxin-2Homo sapiens (human)
RNA metabolic processAtaxin-2Homo sapiens (human)
P-body assemblyAtaxin-2Homo sapiens (human)
stress granule assemblyAtaxin-2Homo sapiens (human)
RNA transportAtaxin-2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (65)

Processvia Protein(s)Taxonomy
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
monooxygenase activityCytochrome P450 2D6Homo sapiens (human)
iron ion bindingCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activityCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2D6Homo sapiens (human)
heme bindingCytochrome P450 2D6Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
actin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
protein bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
alpha-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
metal ion bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
beta-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
integrin bindingSodium-dependent serotonin transporterHomo sapiens (human)
monoatomic cation channel activitySodium-dependent serotonin transporterHomo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent serotonin transporterHomo sapiens (human)
serotonin:sodium:chloride symporter activitySodium-dependent serotonin transporterHomo sapiens (human)
protein bindingSodium-dependent serotonin transporterHomo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent serotonin transporterHomo sapiens (human)
antiporter activitySodium-dependent serotonin transporterHomo sapiens (human)
syntaxin-1 bindingSodium-dependent serotonin transporterHomo sapiens (human)
cocaine bindingSodium-dependent serotonin transporterHomo sapiens (human)
sodium ion bindingSodium-dependent serotonin transporterHomo sapiens (human)
identical protein bindingSodium-dependent serotonin transporterHomo sapiens (human)
nitric-oxide synthase bindingSodium-dependent serotonin transporterHomo sapiens (human)
actin filament bindingSodium-dependent serotonin transporterHomo sapiens (human)
serotonin bindingSodium-dependent serotonin transporterHomo sapiens (human)
monooxygenase activityCytochrome P450 2C19Homo sapiens (human)
iron ion bindingCytochrome P450 2C19Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 2C19Homo sapiens (human)
oxidoreductase activityCytochrome P450 2C19Homo sapiens (human)
(S)-limonene 6-monooxygenase activityCytochrome P450 2C19Homo sapiens (human)
(S)-limonene 7-monooxygenase activityCytochrome P450 2C19Homo sapiens (human)
oxygen bindingCytochrome P450 2C19Homo sapiens (human)
enzyme bindingCytochrome P450 2C19Homo sapiens (human)
heme bindingCytochrome P450 2C19Homo sapiens (human)
(R)-limonene 6-monooxygenase activityCytochrome P450 2C19Homo sapiens (human)
aromatase activityCytochrome P450 2C19Homo sapiens (human)
long-chain fatty acid omega-1 hydroxylase activityCytochrome P450 2C19Homo sapiens (human)
arachidonic acid epoxygenase activityCytochrome P450 2C19Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2C19Homo sapiens (human)
protease bindingSodium-dependent dopamine transporter Homo sapiens (human)
signaling receptor bindingSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
protein bindingSodium-dependent dopamine transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine bindingSodium-dependent dopamine transporter Homo sapiens (human)
amine bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein-containing complex bindingSodium-dependent dopamine transporter Homo sapiens (human)
metal ion bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein phosphatase 2A bindingSodium-dependent dopamine transporter Homo sapiens (human)
heterocyclic compound bindingSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
RNA bindingAtaxin-2Homo sapiens (human)
epidermal growth factor receptor bindingAtaxin-2Homo sapiens (human)
protein bindingAtaxin-2Homo sapiens (human)
mRNA bindingAtaxin-2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (40)

Processvia Protein(s)Taxonomy
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
mitochondrionCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulumCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2D6Homo sapiens (human)
cytoplasmCytochrome P450 2D6Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2D6Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
cell surfaceSodium-dependent noradrenaline transporter Homo sapiens (human)
membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
presynaptic membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
axonSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent serotonin transporterHomo sapiens (human)
focal adhesionSodium-dependent serotonin transporterHomo sapiens (human)
endosome membraneSodium-dependent serotonin transporterHomo sapiens (human)
endomembrane systemSodium-dependent serotonin transporterHomo sapiens (human)
presynaptic membraneSodium-dependent serotonin transporterHomo sapiens (human)
membrane raftSodium-dependent serotonin transporterHomo sapiens (human)
synapseSodium-dependent serotonin transporterHomo sapiens (human)
postsynaptic membraneSodium-dependent serotonin transporterHomo sapiens (human)
serotonergic synapseSodium-dependent serotonin transporterHomo sapiens (human)
synapseSodium-dependent serotonin transporterHomo sapiens (human)
plasma membraneSodium-dependent serotonin transporterHomo sapiens (human)
neuron projectionSodium-dependent serotonin transporterHomo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2C19Homo sapiens (human)
plasma membraneCytochrome P450 2C19Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2C19Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2C19Homo sapiens (human)
cytoplasmCytochrome P450 2C19Homo sapiens (human)
cytoplasmSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
cell surfaceSodium-dependent dopamine transporter Homo sapiens (human)
membraneSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
neuron projectionSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell bodySodium-dependent dopamine transporter Homo sapiens (human)
axon terminusSodium-dependent dopamine transporter Homo sapiens (human)
membrane raftSodium-dependent dopamine transporter Homo sapiens (human)
postsynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
dopaminergic synapseSodium-dependent dopamine transporter Homo sapiens (human)
flotillin complexSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
presynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent dopamine transporter Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cytoplasmAtaxin-2Homo sapiens (human)
Golgi apparatusAtaxin-2Homo sapiens (human)
trans-Golgi networkAtaxin-2Homo sapiens (human)
cytosolAtaxin-2Homo sapiens (human)
cytoplasmic stress granuleAtaxin-2Homo sapiens (human)
membraneAtaxin-2Homo sapiens (human)
perinuclear region of cytoplasmAtaxin-2Homo sapiens (human)
ribonucleoprotein complexAtaxin-2Homo sapiens (human)
cytoplasmic stress granuleAtaxin-2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (170)

Assay IDTitleYearJournalArticle
AID114812Inhibitory activity against Haloperidol catalepsy in mice (sc)1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID179591In vitro inhibition of [14C]norepinephrine uptake into rat hypothalamus1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID1220558Fraction unbound in Beagle dog brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID588210Human drug-induced liver injury (DILI) modelling dataset from Ekins et al2010Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 38, Issue:12
A predictive ligand-based Bayesian model for human drug-induced liver injury.
AID63031Effect on synaptosomal uptake inhibition of Dopamine receptor1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans.
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID611193Inhibition of dopamine reuptake at DAT expressed in CHO-K1 cells2011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues.
AID196022In vitro inhibition of norepinephrine (NE) uptake in synaptosomal preparation of rat brain1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel antidepressant agent and selective inhibitor of norepinephrine uptake.
AID1209457Unbound Cmax in human plasma2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID625293Drug Induced Liver Injury Prediction System (DILIps) validation dataset; compound DILI positive/negative as observed in LTKB-BD2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID752491Inhibition of [3H]5-HT uptake at human SERT expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
AID178876Compound was tested for the inhibition of tetrabenazine-induced sedation in rat, after peroral administration1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel antidepressant agent and selective inhibitor of norepinephrine uptake.
AID752493Inhibition of [3H]dopamine uptake at human DAT expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
AID110071Antagonism of tetrabenazine (TBZ)-induced depression measured in mice by motor activity1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID117080Lethal dose (toxicity) was determined by intraperitoneal administration in mice.1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID112711Compound was evaluated for the inhibitory activity against reserpine hypothermia in mice (sc)1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID114154Antidepressant potential was assessed by the prevention of tetrabenazine-induced ptosis in mice by intraperitoneal administration.1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID360444Displacement of [3H]RTI82 from DAT in rat striatal membrane2007The Journal of biological chemistry, Mar-23, Volume: 282, Issue:12
Localization of cocaine analog [125I]RTI 82 irreversible binding to transmembrane domain 6 of the dopamine transporter.
AID129450Anti-tetrabenazine (TBZ) activity, ability to prevent TBZ-induced ptosis in mice1984Journal of medicinal chemistry, Sep, Volume: 27, Issue:9
Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives.
AID1388100Binding affinity to DAT (unknown origin)2018Journal of medicinal chemistry, 03-22, Volume: 61, Issue:6
Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges.
AID1220554Fraction unbound in Wistar Han rat brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID550778Inhibition of [3H]dopamine reuptake at human DAT expressed in CHOK1 cells by scintillation counting2011Bioorganic & medicinal chemistry, Jan-01, Volume: 19, Issue:1
Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID727349In vivo NET occupancy in sc dosed Long Evans rat thalamus [3H]-MeNER administered 30 mins before [3H]-MeNER challenge measured after 90 mins2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID65018Inhibition of [3H]GBR-12935 binding to the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID717269Inhibition of DAT2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID578421Inhibition of [3H]dopamine reuptake at human recombinant DAT expressed in COS-7 cells by scintillation counting2011Bioorganic & medicinal chemistry letters, Mar-01, Volume: 21, Issue:5
Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor.
AID117221Lethal effect was determined in mice1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID727352In vivo DAT occupancy in sc dosed Long Evans rat striatum assessed as unbound plasma levels equaling 50% occupancy using [3H]-PE2I administered 30 mins before [3H]-PE2I 35428 challenge measured after 60 mins2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID3654Effect on synaptosomal uptake inhibition of 5-hydroxytryptamine (5-HT)1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans.
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID179592In vitro inhibition of [3H]5-HT uptake into rat whole brain1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID1209456Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID171088Concentration inhibiting the uptake of dopamine noradrenaline on synaptosome preparations from rat brain1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID727218Antidepressant activity in sc dosed Sprague-Dawley rat assessed as increase of locomotor activity and stereotypic behavior2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID359911Ratio of IC50 for rat striatum dopamine D2 receptor to IC50 for Wistar rat striatal synaptosomes dopamine transporter-mediated [3H]dopamine uptake1995Journal of natural products, Oct, Volume: 58, Issue:10
Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes.
AID338161Displacement of [3H]WIN-from cocaine site of dopamine transporter1993Journal of natural products, Apr, Volume: 56, Issue:4
The role of receptor binding in drug discovery.
AID114237Serotonergic activity was determined by measuring the potentiation of 5-hydroxytryptophan in mice upon ip administration1989Journal of medicinal chemistry, Mar, Volume: 32, Issue:3
3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1220555Fraction unbound in Sprague-Dawley rat brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID1465046Inhibition of full-length recombinant human DAT expressed in CHOK1 cells assessed as reduction in [3H]dopamine uptake pretreated for 20 mins followed by [3H]dopamine addition measured after 10 mins by scintillation counting method2017Bioorganic & medicinal chemistry letters, 11-01, Volume: 27, Issue:21
Discovery of imidazo[1,2-a]-, [1,2,4]triazolo[4,3-a]-, and [1,2,4]triazolo[1,5-a]pyridine-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5.
AID727347Fraction unbound in Long Evans rat plasma2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID179594In vitro inhibition of [3H]dopamine uptake into rat corpus striatum1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID1209455Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID717268Inhibition of SERT2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID65022Inhibition of [3H]cocaine binding to the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID727356Inhibition of human ERG expressed in CHO-K1 cells by electrophysiological assay2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID110188Antagonism of tetrabenazine (TBZ)-induced depression in mice measured for ptosis1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID625295Drug Induced Liver Injury Prediction System (DILIps) validation dataset; compound DILI positive/negative as observed in Pfizer data2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID187166Inhibition of dopamine (DA) uptake into rat brain synaptosomes1984Journal of medicinal chemistry, Aug, Volume: 27, Issue:8
Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
AID1220560Fraction unbound in human occipital cortex at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID114816Inhibition of tetrabenazine ptosis in mice (sc).1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID147592Effect on synaptosomal uptake inhibition of Noradrenaline (NA)1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID727223Antidepressant activity in Sprague-Dawley rat assessed as reduction of immobility time at 0.3 mg/kg, sc measured for 5 mins by forced swimming test2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID65023Inhibition of [3H]dopamine uptake at the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID112710Dose influencing (+/-) the spontaneous motility in mice, administered intraperitoneally (ip)1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID65638Binding affinity to dopamine transporter (DAT) using [3H]WIN-35428 as a radioligand2000Journal of medicinal chemistry, Nov-02, Volume: 43, Issue:22
2D QSAR modeling and preliminary database searching for dopamine transporter inhibitors using genetic algorithm variable selection of Molconn Z descriptors.
AID196023In vitro inhibition of serotonin uptake in synaptosomal preparation of rat brain1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel antidepressant agent and selective inhibitor of norepinephrine uptake.
AID114151Antidepressant potential was assessed by the potentiation of yohimbine-induced toxicity in mice by intraperitoneal administration.1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines.
AID1220556Fraction unbound in CD-1 mouse brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID727348Ratio of drug level in whole brain to plasma in Long Evans rat2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID179960Inhibition of dopamine uptake in synaptosomal preparation in rat corpus striatum, using [3H]dopamine1984Journal of medicinal chemistry, Nov, Volume: 27, Issue:11
Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID727216Inhibition of DAT in rat synaptosomal membrane2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID727359Intrinsic clearance in human liver microsomes2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID717262Selectivity ratio of Ki for SERT to Ki for human NET2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID196062Inhibition of uptake of tritiated norepinephrine (NE) in rat synaptosomes1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID123597Gross behavioral effects ascertained in mice; W indicates weak stimulant or depressant activity of little significance.1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID359909Inhibition of dopamine transporter-mediated [3H]dopamine uptake in Wistar rat striatal synaptosomes by liquid scintillation spectrometry1995Journal of natural products, Oct, Volume: 58, Issue:10
Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes.
AID47989Compound was tested for potentiating the dopamine-induced hypotension in cats1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID112984Compound was tested for the inhibition of tetrabenazine-induced sedation in mice, after peroral administration1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel antidepressant agent and selective inhibitor of norepinephrine uptake.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1636357Drug activation in human Hep3B cells assessed as human CYP3A4-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID1636440Drug activation in human Hep3B cells assessed as human CYP2D6-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID114815Inhibitory activity against tetrabenazine catalepsy in mice (sc)1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID127692Inhibition of tetrabenazine (TBZ)-induced ptosis in mice (administered ip)1984Journal of medicinal chemistry, Aug, Volume: 27, Issue:8
Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
AID338198Displacement of [3H]WIN-from cocaine site of dopamine transporter assessed as specific binding relative to total binding1993Journal of natural products, Apr, Volume: 56, Issue:4
The role of receptor binding in drug discovery.
AID1220557Fraction unbound in Hartley guinea pig brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID717267Inhibition of rat NET2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID752492Inhibition of [3H]norepinephrine uptake at human NET expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1388098Binding affinity to SERT (unknown origin)2018Journal of medicinal chemistry, 03-22, Volume: 61, Issue:6
Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges.
AID187167Inhibition of serotonin (5-HT) uptake into rat brain synaptosomes1984Journal of medicinal chemistry, Aug, Volume: 27, Issue:8
Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
AID727358Inhibition of human recombinant NET expressed in HEK cells2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID1388099Binding affinity to NET (unknown origin)2018Journal of medicinal chemistry, 03-22, Volume: 61, Issue:6
Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID588209Literature-mined public compounds from Greene et al multi-species hepatotoxicity modelling dataset2010Chemical research in toxicology, Jul-19, Volume: 23, Issue:7
Developing structure-activity relationships for the prediction of hepatotoxicity.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID717266Ex vivo receptor occupancy of NET in rat frontal cortex at 10 mg/kg, po after 1 hr2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID717270Inhibition of human NET2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID727351In vivo DAT occupancy in sc dosed Long Evans rat striatum using [3H]-PE2I administered 30 mins before [3H]-PE2I 35428 challenge measured after 60 mins2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID717263Selectivity ratio of Ki for DAT to Ki for human NET2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
AID112709Amphetamine induced motility in mice1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID196063Inhibition the uptake of tritiated serotonin (5-HT) by the serotonin transporter SERT in rat synaptosomes1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID113147Assessed for thymoleptic activity by its ability to antagonize tetrabenazine ptosis in mice1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID65020Inhibition of [3H]WIN-35428 binding to the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID181670In vitro inhibition of 5-HT uptake in rat brain synaptosomes using [3H]- 5-hydroxytryptamine1984Journal of medicinal chemistry, Sep, Volume: 27, Issue:9
Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID112475Compound was tested for antidepressant activity against reserpine induced ptosis in mice after intraperitoneal administration.; value ranges from 0.13-0.221989Journal of medicinal chemistry, Mar, Volume: 32, Issue:3
3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.
AID179927Inhibition of 5-HT uptake in synaptosomal preparation from rat corpus striatum, using [3H]5-HT1984Journal of medicinal chemistry, Nov, Volume: 27, Issue:11
Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins.
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID727354In vivo NET occupancy in sc dosed Long Evans rat thalamus assessed as unbound plasma levels equaling 50% occupancy using [3H]-MeNER administered 30 mins before [3H]-MeNER challenge measured after 90 mins2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID227718Binding energy by using the equation deltaG obsd = -RT ln KD1984Journal of medicinal chemistry, Dec, Volume: 27, Issue:12
Functional group contributions to drug-receptor interactions.
AID727355Inhibition of human recombinant SERT expressed in HEK cells2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID65016Inhibition of [3H]BTCP binding to the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID65019Inhibition of [3H]WIN-35065-2 binding to the dopamine transporter.1992Journal of medicinal chemistry, Mar-20, Volume: 35, Issue:6
Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.
AID181420Compound was evaluated for the inhibitory activity against inducing stereotypy in rats (sc)1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID727346Antidepressant activity in Sprague-Dawley rat assessed as reduction of immobility time at 1 to 30 mg/kg, sc measured for 5 mins by forced swimming test2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID625276FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of most concern for DILI2011Drug discovery today, Aug, Volume: 16, Issue:15-16
FDA-approved drug labeling for the study of drug-induced liver injury.
AID727360Inhibition of CYP2D6 (unknown origin)2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID181669In vitro inhibition of norepinephrine uptake in rat brain synaptosomes using [3H]NE1984Journal of medicinal chemistry, Sep, Volume: 27, Issue:9
Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1636356Drug activation in human Hep3B cells assessed as human CYP2C9-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID1220559Fraction unbound in cynomolgus monkey brain homogenates at 1 uM after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 39, Issue:7
Species independence in brain tissue binding using brain homogenates.
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID187165Inhibition of norepinephrine (NE) into rat brain synaptosomes1984Journal of medicinal chemistry, Aug, Volume: 27, Issue:8
Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
AID359910Ratio of IC50 for rat striatum dopamine D1 receptor to IC50 for Wistar rat striatal synaptosomes dopamine transporter-mediated [3H]dopamine uptake1995Journal of natural products, Oct, Volume: 58, Issue:10
Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes.
AID195890In vitro inhibition of dopamine (DA) uptake in synaptosomal preparation of rat brain1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel antidepressant agent and selective inhibitor of norepinephrine uptake.
AID727217Inhibition of NET in rat synaptosomal membrane2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID127690Inhibition of tetrabenazine (TBZ)-induced depression of motor activity (MA) in mice (administered ip)1984Journal of medicinal chemistry, Aug, Volume: 27, Issue:8
Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
AID196059Inhibition of the uptake of tritiated dopamine (DA) in rat synaptosomes1987Journal of medicinal chemistry, Aug, Volume: 30, Issue:8
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.
AID179973Inhibition of norepinephrine uptake in synaptosomal preparation fro rat hypothalamus, using [3H]norepinephrine1984Journal of medicinal chemistry, Nov, Volume: 27, Issue:11
Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins.
AID727357Inhibition of human recombinant DAT expressed in HEK cells2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
AID115595Ability to modify turning behavior of mice after intraperitoneal administration.1989Journal of medicinal chemistry, Mar, Volume: 32, Issue:3
3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,058)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990623 (58.88)18.7374
1990's239 (22.59)18.2507
2000's114 (10.78)29.6817
2010's67 (6.33)24.3611
2020's15 (1.42)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 32.32

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index32.32 (24.57)
Research Supply Index7.12 (2.92)
Research Growth Index4.20 (4.65)
Search Engine Demand Index50.49 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (32.32)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials111 (9.85%)5.53%
Reviews45 (3.99%)6.00%
Case Studies64 (5.68%)4.05%
Observational0 (0.00%)0.25%
Other907 (80.48%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]