Page last updated: 2024-12-06

dexfenfluramine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Dexfenfluramine is a chiral amphetamine derivative that was marketed as an appetite suppressant in the 1990s. It was withdrawn from the market in 1997 due to concerns about its potential to cause valvular heart disease. Dexfenfluramine is a selective serotonin reuptake inhibitor (SSRI) that acts primarily on the central nervous system. It is synthesized by a multi-step process that starts with the reaction of phenylacetone with N-methylphenethylamine. Dexfenfluramine is a potent appetite suppressant that works by increasing serotonin levels in the brain. Dexfenfluramine was studied extensively for its potential to treat obesity. It was found to be effective in promoting weight loss, but it also carried a risk of serious side effects. Despite being withdrawn from the market, dexfenfluramine continues to be studied for its potential therapeutic benefits. Researchers are investigating its use in treating conditions such as binge eating disorder, Tourette's syndrome, and obsessive-compulsive disorder. Dexfenfluramine is a complex compound with both potential therapeutic benefits and risks. Its history highlights the importance of careful safety evaluation before any drug is marketed for human use.'

Dexfenfluramine: The S-isomer of FENFLURAMINE. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

(S)-fenfluramine : The S-enantiomer of fenfluramine. It stimulates the release of serotonin and selectively inhibits its reuptake, but unlike fenfluramine it does not possess catecholamine agonist activity. It was formerly given by mouth as the hydrochloride in the treatment of obesity, but, like fenfluramine, was withdrawn wolrdwide following reports of valvular heart defects. [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 CID66265
CHEMBL ID248702
CHEBI ID439329
SCHEMBL ID16706
MeSH IDM0030010

Synonyms (54)

Synonym
isolipan
PDSP2_001403
benzeneethanamine, n-ethyl-alpha-methyl-3-(trifluoromethyl)-, (s)-
d-fenfluramine
dexfenfluramina [spanish]
hsdb 7356
dexfenfluramine [inn:ban]
phenethylamine, n-ethyl-alpha-methyl-m-(trifluoromethyl)-, (s)-
dexfenfluraminum [latin]
PDSP1_000695
PDSP1_001419
(+)-fenfluramine
d-n-ethyl-alpha-methyl-m-trifluoromethylphenethylamine
(s)-fenfluramine
dexfenfluramine
dextrofenfluramine
DB01191
(s)-n-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
PDSP2_000685
s 5614
CHEMBL248702
j13.711a ,
fenfluramine d-form
D07805
3239-44-9
dexfenfluramine (inn)
dexfenfluramina
(2s)-n-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
chebi:439329 ,
dexfenfluraminum
unii-e35r3g56ov
e35r3g56ov ,
bdbm85596
cas_3239-45-0
phenethylamine, n-ethyl-.alpha.-methyl-m-(trifluoromethyl)-, (s)-
benzeneethanamine, n-ethyl-.alpha.-methyl-3-(trifluoromethyl)-, (s)-
(+)-(s)-n-ethyl-a-methyl-m-(trifluoromethyl)phenethylamine
d-(+)-fenfluramine
benzeneethanamine, n-ethyl-.alpha.-methyl-3-(trifluoromethyl)-, (.alpha.s)-
fenfluramine d-form [mi]
(.alpha.s)-n-ethyl-.alpha.-methyl-3-(trifluoromethyl)benzeneethanamine
dexfenfluramine [vandf]
5220-91-7
dexfenfluramine [hsdb]
dexfenfluramine [who-dd]
(s)-(+)-fenfluramine
dexfenfluramine [inn]
SCHEMBL16706
ethyl[(2s)-1-[3-(trifluoromethyl)phenyl]propan-2-yl]amine
ip001
Q3025599
DTXSID001025754
dbgivfwfufkiqn-vifpvbqesa-n
(alphas)-n-ethyl-alpha-methyl-3-(trifluoromethyl)benzeneethanamine

Research Excerpts

Effects

ExcerptReferenceRelevance
"Dexfenfluramine has been widely used as an appetite suppressant in the treatment of obesity. "( Metabolism of dexfenfluramine in human liver microsomes and by recombinant enzymes: role of CYP2D6 and 1A2.
Ahokas, JT; Battaglia, SE; Ching, MS; Ghabrial, H; Gross, AS; Haritos, VS; Pelkonen, O; Smallwood, RA; Taavitsainen, P, 1998
)
2.1

Treatment

ExcerptReferenceRelevance
"Pre-treatment with dexfenfluramine, memantine, and MTEP produced decreases in candy consumption without altering candy-seeking behaviour."( Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder.
Bisaga, A; Danysz, W; Foltin, RW, 2008
)
0.66

Toxicity

ExcerptReferenceRelevance
"The removal of 5 pharmaceuticals from the market in a 12-month period because of unexpected adverse events raised concerns about the adequacy of the drug review process at the US Food and Drug Administration (FDA)."( The safety of newly approved medicines: do recent market removals mean there is a problem?
Friedman, MA; Hass, AE; Lumpkin, MM; Shuren, JE; Thompson, LJ; Woodcock, J, 1999
)
0.3
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32

Pharmacokinetics

ExcerptReferenceRelevance
" 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

In the 1990s, phentermine was combined with either fenfluramine or its active enantiomer dexfen fluramine to promote weight loss.

ExcerptReferenceRelevance
"Free feeding rats given supplementary 1 h access per day to a palatable dessert test meal were tested for the anorectic effect of dehydroepiandrosterone alone or in combination with either the serotonin releasing agent dexfenfluramine or the norepinephrine uptake inhibitor thionisoxetine (LY 368975)."( Anorectic effect of dehydroepiandrosterone combined with dexfenfluramine or thionisoxetine.
Marshall, M; Robertson, K; Rowland, NE, 2001
)
0.74
" In contrast, SR 141716 in combination with naloxone had a significantly supra-additive anorectic action."( Effects of the cannabinoid receptor antagonist SR 141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats.
Mukherjee, M; Robertson, K; Rowland, NE, 2001
)
0.53
"In the 1990s, phentermine was combined with either fenfluramine or its active enantiomer dexfenfluramine to promote weight loss."( Effects of acute administration of phentermine, alone or in combination with dexfenfluramine, on pain reactivity in the adult rat.
Wellman, PJ, 2008
)
0.8

Bioavailability

ExcerptReferenceRelevance
" Following oral ingestion, sibutramine is well absorbed and undergoes extensive first pass metabolism."( Anti-obesity drugs: what does sibutramine offer? An analysis of its potential contribution to obesity treatment.
De Leeuw, IH; Van Gaal, LF; Wauters, MA, 1998
)
0.3
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."( Hologram QSAR model for the prediction of human oral bioavailability.
Andricopulo, AD; Moda, TL; Montanari, CA, 2007
)
0.34

Dosage Studied

ExcerptRelevanceReference
" Doppler echocardiographic examination should be performed after prolonged exposure (> 3 months) or a high dosage of these drugs, in circumstances such as the presence of cardiovascular symptoms, a cardiac murmur, or an uncertain cardiac examination because of weight of patients."( [Appetite suppressants and heart valve disorders].
Adams, C; Cohen, A, 1999
)
0.3
"2 times the equivalent human daily dosage according to body surface area."( Impact of antenatal exposure of mice to fenfluramine on cardiac development and long-term growth of the offspring.
Christensen, HD; Gonzalez, CL; Kupiec, TC; Paulsen, AL; Rayburn, WF; Sienko, AE; Stewart, JD, 2000
)
0.31
") using the same dosing regimen as described above."( Sibutramine does not decrease the number of 5-HT re-uptake sites in rat brain and, like fluoxetine, protects against the deficits produced by dexfenfluramine.
Cheetham, SC; Heal, DJ; Slater, NA; Viggers, JA, 2000
)
0.51
" This compound was found to be a high-affinity ligand for MCHr1 and a potent inhibitor of MCH-mediated Ca(2+) release, showed good plasma and CNS exposure upon oral dosing in diet-induced obese mice, and is the first reported MCHr1 antagonist that is efficacious upon oral dosing in a chronic model of weight loss."( Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity.
Brodjian, S; Brune, M; Bush, E; Collins, CA; Dayton, B; Gao, J; Hernandez, LE; Judd, AS; Kym, PR; Marsh, KC; Mulhern, M; Sham, HL; Shapiro, R; Souers, AJ; Vasudevan, A; Wodka, D, 2005
)
0.33
" DIO rats were dosed orally with vehicle, Imidazole 24b (1, 3 or 10 mg/kg), or dexfenfluramine (3 mg/kg) for 2 weeks."( Characterization of a novel and selective cannabinoid CB1 receptor inverse agonist, Imidazole 24b, in rodents.
Camacho, RE; Feng, Y; Finke, PE; Fong, TM; Goulet, MT; Guan, X; Hagmann, WK; Macintyre, DE; Macneil, DJ; Marsh, DJ; Metzger, JM; Mills, SG; Plummer, CW; Rosko, KM; Shah, SK; Shearman, LP; Spann, SK; Strack, AM; Stribling, DS; Tong, S; Truong, Q; Van der Ploeg, LH; Wang, J; Yu, H, 2008
)
0.57
" Complete dose-response functions for the effects of the drugs on food pellet intake on days that candy was not available were determined before, during, and after the period of access to candy."( Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons.
Foltin, RW, 2011
)
0.37
" Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1(-/-) mice."( Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension.
Dempsie, Y; Loughlin, L; MacLean, MR; MacRitchie, NA; Mair, KM; Morecroft, I; Nilsen, M; White, K; Wright, AF, 2013
)
1.83
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
appetite depressantAgent that is used to decrease appetite.
serotonergic agonistAn agent that has an affinity for serotonin receptors and is able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. Serotonin agonists are used as antidepressants, anxiolytics, and in the treatment of migraine disorders.
serotonin uptake inhibitorA compound that specifically inhibits the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent.
[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
fenfluramineA secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reuptake pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertension.
[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 (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
5-hydroxytryptamine receptor 1ARattus norvegicus (Norway rat)IC50 (µMol)3.40300.00031.38338.4000AID625190
5-hydroxytryptamine receptor 1ARattus norvegicus (Norway rat)Ki1.94400.00010.739610.0000AID625190
5-hydroxytryptamine receptor 1BRattus norvegicus (Norway rat)IC50 (µMol)3.40300.00051.48357.8000AID625190
5-hydroxytryptamine receptor 1BRattus norvegicus (Norway rat)Ki1.94400.00031.29679.2440AID625190
Sigma non-opioid intracellular receptor 1Homo sapiens (human)IC50 (µMol)0.51600.00030.70285.3660AID625223
Sigma non-opioid intracellular receptor 1Homo sapiens (human)Ki0.21700.00000.490110.0000AID625223
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (5)

Processvia Protein(s)Taxonomy
lipid transportSigma non-opioid intracellular receptor 1Homo sapiens (human)
nervous system developmentSigma non-opioid intracellular receptor 1Homo sapiens (human)
G protein-coupled opioid receptor signaling pathwaySigma non-opioid intracellular receptor 1Homo sapiens (human)
regulation of neuron apoptotic processSigma non-opioid intracellular receptor 1Homo sapiens (human)
protein homotrimerizationSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
G protein-coupled opioid receptor activitySigma non-opioid intracellular receptor 1Homo sapiens (human)
protein bindingSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
nuclear envelopeSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear inner membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear outer membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulum membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
lipid dropletSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytosolSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic densitySigma non-opioid intracellular receptor 1Homo sapiens (human)
membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
growth coneSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytoplasmic vesicleSigma non-opioid intracellular receptor 1Homo sapiens (human)
anchoring junctionSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic density membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (73)

Assay IDTitleYearJournalArticle
AID496828Antimicrobial activity against Leishmania donovani2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' 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]
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID259799Reduction in food intake in food-deprived rats after 4 hrs of administration of 3 mg/kg2006Bioorganic & medicinal chemistry letters, Feb, Volume: 16, Issue:3
Pyrrolo(iso)quinoline derivatives as 5-HT(2C) receptor agonists.
AID409953Inhibition of mouse liver MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID540230Dose normalised AUC in rat after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID250902Change in body weight of mice on day 14 following peroral administration at 10 mg/kg, 4 times a day; n = 12; body weight at day 0 = 43.2 g2005Journal of medicinal chemistry, Mar-10, Volume: 48, Issue:5
Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID605094Antiobesity activity in wild type 14 days diet-induced obese rat model assessed as reduction in body weight at 3 mg/kg, po qd2010Bioorganic & medicinal chemistry letters, Aug-01, Volume: 20, Issue:15
Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity.
AID497005Antimicrobial activity against Pneumocystis carinii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID540231Dose normalised AUC in dog after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID252204Body weight of the mice after treatment with the compound (10 mg/kg, p.o.) on day 0 (Vehicle=45.0 1 0.7); n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
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.
AID496826Antimicrobial activity against Entamoeba histolytica2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID250125Mean cumulative food intake of mice on day 7 after treatment with compound at 10 mg/kg; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID496817Antimicrobial activity against Trypanosoma cruzi2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
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]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID409956Inhibition of mouse brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
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.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID496830Antimicrobial activity against Leishmania major2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
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.
AID496820Antimicrobial activity against Trypanosoma brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496823Antimicrobial activity against Trichomonas vaginalis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID409954Inhibition of mouse brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID496821Antimicrobial activity against Leishmania2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496829Antimicrobial activity against Leishmania infantum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID250123Mean cumulative food intake of mice on day 5 after treatment with compound at 10 mg/kg; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' 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.
AID409955Inhibition of mouse liver MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID496825Antimicrobial activity against Leishmania mexicana2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496832Antimicrobial activity against Trypanosoma brucei rhodesiense2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
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
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID496818Antimicrobial activity against Trypanosoma brucei brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID250138Mean cumulative food intake of mice on day 11 after treatment with compound at 10 mg/kg; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID540232Dose normalised AUC in monkey after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
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]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID539464Solubility of the compound in 0.1 M phosphate buffer at 600 uM at pH 7.4 after 24 hrs by LC/MS/MS analysis2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID496824Antimicrobial activity against Toxoplasma gondii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID479950Antiobesity activity in diet-induced obese rat assessed as body weight loss at 3 mg/kg, po after 18 hrs of last dose on day 72010Journal of medicinal chemistry, May-27, Volume: 53, Issue:10
Discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity.
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]
AID496831Antimicrobial activity against Cryptosporidium parvum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID540233Dose normalised AUC in human after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID479951Antiobesity activity in diet-induced obese rat assessed as body weight loss at 3 mg/kg, po after 7 days2010Journal of medicinal chemistry, May-27, Volume: 53, Issue:10
Discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity.
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.
AID253108Percent change of mice body weight after treatment with the compound (10 mg/kg, p.o.) to that of vehicle; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID311524Oral bioavailability in human2007Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24
Hologram QSAR model for the prediction of human oral bioavailability.
AID496827Antimicrobial activity against Leishmania amazonensis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
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]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
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.
AID250121Mean cumulative food intake of mice on day 1 after treatment with compound at 10 mg/kg; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID250140Mean cumulative food intake of mice on day 14 after treatment with compound at 10 mg/kg; n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
AID252199Body weight of mice on day 14 following peroral administration at 10 mg/kg, 4 times a day; n = 122005Journal of medicinal chemistry, Mar-10, Volume: 48, Issue:5
Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity.
AID252206Body weight of the mice after treatment with the compound (10 mg/kg, p.o.) on day 14 (Vehicle=46.9 1 0.8); n=122005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (211)

TimeframeStudies, This Drug (%)All Drugs %
pre-19904 (1.90)18.7374
1990's56 (26.54)18.2507
2000's123 (58.29)29.6817
2010's25 (11.85)24.3611
2020's3 (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: 45.00

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index45.00 (24.57)
Research Supply Index5.50 (2.92)
Research Growth Index5.96 (4.65)
Search Engine Demand Index66.09 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (45.00)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials17 (7.52%)5.53%
Reviews32 (14.16%)6.00%
Case Studies15 (6.64%)4.05%
Observational1 (0.44%)0.25%
Other161 (71.24%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
"Investigation of Serotonin Neurotransmission in Ecstasy Users Employing Combined Dexfenfluramine Challenge and Positron Emission Tomography: a Functional Probe to Assess MDMA Neurotoxicity" [NCT01296802]50 participants (Actual)Interventional2006-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]