Page last updated: 2024-11-04

flurazepam

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Description

Flurazepam is a benzodiazepine medication that is used to treat insomnia. It is a Schedule IV controlled substance in the United States. Flurazepam was first synthesized in 1964 by researchers at Hoffmann-La Roche. It acts as a sedative-hypnotic by enhancing the effects of the neurotransmitter GABA in the brain. Flurazepam is rapidly absorbed from the gastrointestinal tract and has a half-life of approximately 25-40 hours. It is metabolized in the liver and excreted in the urine. Flurazepam is effective in treating insomnia, but it can also cause side effects, including drowsiness, dizziness, and confusion. It can also be habit-forming and should not be taken for extended periods of time. Flurazepam has been studied for its potential to treat other conditions, such as anxiety, seizures, and muscle spasms. However, it is not currently approved for these uses in the United States.'

Flurazepam: A benzodiazepine derivative used mainly as a hypnotic. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

flurazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a 2-(diethylamino)ethyl group, 2-fluorophenyl group and chloro group at positions 1, 5 and 7, respectively. It is a partial agonist of GABAA receptors and used for the treatment of insomnia. [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 CID3393
CHEMBL ID968
CHEBI ID5128
SCHEMBL ID29793
MeSH IDM0008645

Synonyms (71)

Synonym
insumin
7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-one
hsdb 3085
2h-1,4-benzodiazepin-2-one, 1,3-dihydro-7-chloro-1-(2-(diethylamino)ethyl)-5-(o-fluorophenyl)-
flurazepam [inn:ban:jan]
dalmane-r
7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-one
brn 0767925
2h-1,4-benzodiazepin-2-one, 7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1,3-dihydro-
flurazepamum [inn-latin]
7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1h-1,4-benzodiazepin-2(3h)-one
ro-5-6901/3
einecs 241-591-7
2h-1,4-benzodiazepin-2-one, 7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-
2h-1,4-benzodiazepin-2-one, 7-chloro-1-[2-(diethylamino)ethyl]-5-(o-fluorophenyl)-1,3-dihydro-
flurazepam hcl
flurazepam
DB00690
D00329
insumin (tn)
flurazepam (jan/inn)
17617-23-1
NCGC00164573-01
CHEMBL968
A812156
7-chloranyl-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-one
7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-one
7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1h-benzo[e][1,4]diazepin-2(3h)-one
flurazepamum
5-24-04-00322 (beilstein handbook reference)
unii-ihp475989u
ihp475989u ,
dtxcid803071
cas-17617-23-1
dtxsid1023071 ,
tox21_112201
fl7 ,
stauroderm
felmane
noctosom
flurazepam [vandf]
flurazepam [hsdb]
flurazepam [mi]
flurazepam [jan]
7-chloro-1-(2-(diethylamino)ethyl)-5-(o-fluorophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-one
flurazepam [mart.]
2h-1,4-benzodiazepin-2-one, 7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1,3-dihydro
flurazepam [who-dd]
flurazepam [inn]
AKOS015889971
gtpl7188
7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-2,3-dihydro-1h-1,4-benzodiazepin-2-one
ro-56901
SCHEMBL29793
tox21_112201_1
NCGC00164573-02
7-chloro-1-[2-(diethylamino)ethyl]-5-(o-fluorophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-one
7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-one #
ro 56901/3
CHEBI:5128 ,
flurazepam 1.0 mg/ml in methanol
flurazepam 0.1 mg/ml in methanol
(e)-7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1h-benzo[e][1,4]diazepin-2(3h)-one
Q418998
17617-23-1(free base)
2h-1,4-benzodiazepin-2-one, 7-chloro-1-(2-(diethylamino)ethyl)-5-(o-fluorophenyl)-1,3-dihydro-
flurazepamum (inn-latin)
7-chloro-1-(2-(diethylamino)ethyl)-5-(2-fluorophenyl)-1h-1, 4-benzodiazepin- 2(3h)-one
flurazepam (mart.)
n05cd01
flurazepam, 1mg/ml in methanol

Research Excerpts

Overview

Flurazepam hydrochloride is a benzodiazepine derivative marketed for use as a hypnotic agent. The optimum dose for use in general practice is 15 mg at night.

ExcerptReferenceRelevance
"Flurazepam is a benzodiazepine, a widely prescribed hypnotic drug for use in sleep disorders."( Acute flurazepam intoxication: a case report.
Chiarotti, M; De Giorgio, F; Martello, S; Oliva, A, 2006
)
1.54
"Flurazepam is a drug which is rapidly metabolized into a series of metabolites."( [Preliminary report on the blood levels of Flurazepam administered in two different pharmaceutical formulations].
Ghirardi, P; Grosso, F; Marzo, A; Parenti, MA, 1979
)
1.24
"Flurazepam serves as a precursor for at least two rapidly appearing and rapidly cleared metabolites that may contribute to sleep induction and are nonaccumulating."( Pharmacokinetic properties of benzodiazepine hypnotics.
Abernethy, DR; Divoll, M; Greenblatt, DJ; Harmatz, JS; Shader, RI, 1983
)
0.99
"Flurazepam is a long elimination half-life drug, and there is significant daytime sedation during short term use; with continued use this effect diminishes."( Sleep laboratory studies of hypnotic drugs: efficacy and withdrawal effects.
Kales, A; Kales, JD, 1983
)
0.99
"Flurazepam is a benzodiazepine (BZD) derivative and a category IV controlled substance. "( Flurazepam toxicosis in two dogs.
Beier, E; Bischoff, K, 1997
)
3.18
"Flurazepam thus appears to be an effective hypnotic drug with the optimum dose for use in general practice being 15 mg at night."( A clinical and psychometric evaluation of flurazepam.
Salkind, MR; Silverstone, T, 1975
)
1.24
"Flurazepam hydrochloride is a benzodiazepine derivative marketed for use as a hypnotic agent. "( Flurazepam hydrochloride, a benzodiazepine hypnotic.
Greenblatt, DJ; Koch-Weser, J; Shader, RI, 1975
)
3.14
"Flurazepam (F) is an extensively prescribed hypnotic (Dalmane) whose in vivo activity has been suggested to be due to its primary metabolites, hydroxyethyl flurazepam (HEF) and N-desalkylflurazepam (DAF). "( The effect of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole, on the in vivo metabolism and pharmacologic activity of flurazepam.
Capello, S; DeGrazia, F; Garland, W; Henderson, L; Liberato, D; Town, C,
)
1.78
"Flurazepam also proved to be an effective anticonvulsant in tests against 3-mercaptopropionic acid."( Anticonvulsant and convulsant properties of flurazepam.
Kalichman, MW, 1985
)
1.25

Effects

ExcerptReferenceRelevance
"Flurazepam has relatively minor effects upon rapid eye movement (REM) sleep and does not lead to REM rebound; this may reduce the likelihood of drug dependence."( Flurazepam hydrochloride, a benzodiazepine hypnotic.
Greenblatt, DJ; Koch-Weser, J; Shader, RI, 1975
)
2.42

Actions

Flurazepam was able to inhibit the daunorubicin efflux in 80%. It does not cause enzyme induction and probably presents little hazard of abuse.

ExcerptReferenceRelevance
"Flurazepam was able to inhibit the daunorubicin efflux in 80%."( Flurazepam inhibits the P-glycoprotein transport function: an insight to revert multidrug-resistance phenotype.
Cordeiro-da-Silva, A; de Castro, B; Gameiro, P; Lima, SA; Tavares, J, 2008
)
2.51
"Flurazepam does not cause enzyme induction and probably presents little hazard of abuse or overdosage."( Flurazepam hydrochloride, a benzodiazepine hypnotic.
Greenblatt, DJ; Koch-Weser, J; Shader, RI, 1975
)
2.42
"Flurazepam did not inhibit diacylglycerol production by PLC."( Human platelet activation by bacterial phospholipase C: mechanism of inhibition by flurazepam.
Anwer, K; Romstedt, K; Wallace, D, 1988
)
1.22

Treatment

Pretreatment with flurazepam or chlordiazepoxide markedly enhanced the cataleptic response of mice to delta-9-tetrahydrocannabinol (THC; 5-20 mg/kg i.p.)

ExcerptReferenceRelevance
"Flurazepam-treated patients had a significantly more severe rating of adverse reactions than did placebo-treated patients."( Comparative efficacy of estazolam, flurazepam, and placebo in outpatients with insomnia.
Dominguez, RA; Goldstein, BJ; Jacobson, AF; Steinbook, RM, 1986
)
1.27
"Pretreatment with flurazepam (3 mg/kg s.c.) or chlordiazepoxide (5.5-30 mg/kg s.c.) at an ambient temperature of 34 degrees C, markedly enhanced the cataleptic response of mice to delta-9-tetrahydrocannabinol (THC; 5-20 mg/kg i.p.) as measured in a bar test. "( Delta-9-tetrahydrocannabinol-induced catalepsy in mice is enhanced by pretreatment with flurazepam or chlordiazepoxide.
Greentree, SG; Pertwee, RG, 1988
)
0.83

Toxicity

The LD50 of diazepam and chlordiazepoxide were not modified by physostigmine administration, but that of flurazepam was significantly decreased.

ExcerptReferenceRelevance
"To assess the potential hazards of flurazepam (Dalmane) therapy of insomnia in the elderly, the relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients."( Toxicity of high-dose flurazepam in the elderly.
Allen, MD; Greenblatt, DJ; Shader, RI, 1977
)
0.85
"Findings from a four-city study of the beneficial and adverse effects of hypnotics are reported."( The beneficial and adverse effects of hypnotics.
Balter, MB; Uhlenhuth, EH, 1991
)
0.28
" No marked adverse reactions were found in any area for any group."( Clinical safety of flurazepam and midazolam during 14-day use in chronic insomniacs.
Hauri, P; Kripke, D; Roehrs, T; Sateia, MJ, 1990
)
0.61
" The LD50 of diazepam and chlordiazepoxide were not modified by physostigmine administration, but that of flurazepam was significantly decreased."( Effects of physostigmine on benzodiazepine toxicity.
Bamonte, F; Ongini, E; Parravicini, L, 1981
)
0.48
"Pharmacoepidemiology investigates associations between time-varying medication use/dose and risk of adverse events."( Comparison of alternative models for linking drug exposure with adverse effects.
Abrahamowicz, M; Beauchamp, ME; Sylvestre, MP, 2012
)
0.38

Pharmacokinetics

The final metabolite, desalkylflurazepam, appears slowly, but has a long half-life ranging from 40 to 150 h. Quzepam and flurazEPam share pharmacokinetic properties that result in prevention of early-morning insomnia, daytime rebound anxiety, and withdrawal rebound insomnia.

ExcerptReferenceRelevance
"Quazepam and flurazepam share pharmacokinetic properties that result in prevention of early-morning insomnia, daytime rebound anxiety, and withdrawal rebound insomnia."( Quazepam and flurazepam: differential pharmacokinetic and pharmacodynamic characteristics.
Battista, D; Hilbert, JM, 1991
)
1.02
"To assess pharmacodynamic and pharmacokinetic properties of acute, subchronic and withdrawn quazepam, a single-blind, longitudinal study was run in eight male, healthy young volunteers."( Longitudinal study on pharmacodynamics and pharmacokinetics of acute, steady-state and withdrawn quazepam.
Kauert, G; Klausnitzer, W; Schaffler, K; Wauschkuhn, CH, 1989
)
0.28
" This metabolite appeared in serum rapidly (within 2 h), reached a peak between 2 and 12 h and declined slowly, with an elimination half-life of about 90 h on average."( Pharmacokinetics of flutoprazepam, a novel benzodiazepine drug, in normal subjects.
Barzaghi, N; Leone, L; Monteleone, M; Perucca, E; Tomasini, G,
)
0.13
" The method was applied to sublingual pharmacokinetic studies of quazepam in healthy volunteers."( Liquid chromatographic assay and pharmacokinetics of quazepam and its metabolites following sublingual administration of quazepam.
Ellinwood, EH; Gupta, SK, 1988
)
0.27
"Large differences exist among the various benzodiazepines with regard to their pharmacokinetic properties and metabolism in man."( Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles.
Breimer, DD; Jochemsen, R, 1984
)
0.27

Compound-Compound Interactions

ExcerptReferenceRelevance
" These effects were examined independently and in combination with ethanol effects."( Effects of flurazepam and zopiclone on the performance of chronic insomniac patients: a study of ethanol-drug interaction.
Buck, L; Csima, A; Mamelak, M; Price, V; Smiley, A, 1987
)
0.66
"Two benzodiazepine hypnotics were administered alone or in combination with alcohol to normal male volunteers."( A comparison of two benzodiazepine hypnotics administered with alcohol.
Goodwin, DW; Hill, SY; Hopper, S; Mendelson, WB; Reichman, JB, 1982
)
0.26

Bioavailability

ExcerptReferenceRelevance
" Pharmacokinetics and bioavailability are certainly altered by such modifications, usually in a positive sense."( Peptide derivatives as prodrugs.
Thomas, WA, 1986
)
0.27
" SAS 643 bioavailability and action at the central nervous system (CNS) level is established."( Quantitative EEG and behavioral effects in volunteers of a new benzodiazepine (SAS 643) in relation to drug plasma concentration.
Cabri, M; Montano, VF; Rosadini, G; Sannita, WG, 1981
)
0.26
" Temazepam has a relatively slow rate of absorption and an intermediate half-life in the range of 10 to 20 hours."( Pharmacokinetic properties of benzodiazepine hypnotics.
Abernethy, DR; Divoll, M; Greenblatt, DJ; Harmatz, JS; Shader, RI, 1983
)
0.27
" The administration of Flurazepam in solution allows a more rapid enteral absorption rate and consequently the levels of the unchanged drug are measurable over a 2 hour period."( [Preliminary report on the blood levels of Flurazepam administered in two different pharmaceutical formulations].
Ghirardi, P; Grosso, F; Marzo, A; Parenti, MA, 1979
)
0.83
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

The dose-response curve for diazepam asymptoted over the range 15 to 100 mg/kg, ip. The relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients.

ExcerptRelevanceReference
" The clinical implications are discussed with regard to the time of peak effectiveness of the drug, dosage recommendations and schedule, minimizing possible effects of the drug on daytime performance, and the rationale and method for using drug holidays in the treatment regimen."( Sleep laboratory studies of flurazepam: a model for evaluating hypnotic drugs.
Bixler, EO; Kales, A; Kales, JD; Scharf, M, 1976
)
0.55
" The dose-response curve for diazepam asymptoted over the range 15 to 100 mg/kg, ip whereas dose-response curves for flurazepam and chloridazepoxide were more linear."( Discriminable effects of benzodiazepines.
Overton, DA, 1976
)
0.46
"To assess the potential hazards of flurazepam (Dalmane) therapy of insomnia in the elderly, the relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients."( Toxicity of high-dose flurazepam in the elderly.
Allen, MD; Greenblatt, DJ; Shader, RI, 1977
)
0.85
" Some interesting theoretical and practical questions about the measurement of sustained efficacy of hypnotics in situations of repetitive dosing were addressed by the study."( Methodology for demonstrating sustained efficacy of hypnotics: a comparative study of triazolam and flurazepam.
Lasagna, L; Sundaresan, PR; Wardell, WM; Weintraub, M, 1979
)
0.48
"3 PB, tested at concentrations up to 80 muM, produced variable effects on the dose-response curve to GABA."( Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs.
Bowery, NG; Dray, A, 1978
)
0.26
" A significant dose-response curve was obtained with triazolam and flurazepam for some of the parameters."( Comparison of the hypnotic activity of triazolam, flurazepam hydrochloride, and placebo.
Sunshine, A, 1975
)
0.74
" In long-term dosage studies, flurazepam's efficacy persists while other hypnotics become ineffective."( Flurazepam hydrochloride, a benzodiazepine hypnotic.
Greenblatt, DJ; Koch-Weser, J; Shader, RI, 1975
)
1.99
" The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range."( The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats.
Barsuhn, C; Lahti, RA, 1975
)
0.25
" The benzodiazepine effect was evaluated by the shift in the isoguvacine dose-response curve in the absence, then presence, of diazepam."( Reduction in potency of selective gamma-aminobutyric acidA agonists and diazepam in CA1 region of in vitro hippocampal slices from chronic flurazepam-treated rats.
Tietz, EI; Xie, XH, 1992
)
0.49
" Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves."( Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat.
Lindgren, S; Meyerson, B; Westerling, P, 1991
)
0.28
" Plasma concentrations for each hypnotic after dosing were measured by electron-capture gas-liquid chromatography."( Intranasal absorption of flurazepam, midazolam, and triazolam in dogs.
Amidon, GL; Goldberg, A; Lui, CY, 1991
)
0.58
" A comparison of results from dose-response curves with isoboles showed good agreement."( Evaluation of experimental combined toxicity by use of dose-frequency curves: comparison with theoretical additivity as well as independence.
Dittrich, P; Lenk, W; Pöch, G; Reiffenstein, RJ; Schuster, A, 1990
)
0.28
"Sixty insomniac patients participated in a controlled double-blind parallel group study designed to investigate the dose-response relationship of zopiclone."( A dose-range finding study of zopiclone in insomniac patients.
Dimitri, R; Le Morvan, P; Nair, NP; Schwartz, G; Thavundayil, JX, 1990
)
0.28
" It is shown that theoretical independent isoboles can either represent additive, overadditive, or underadditive interactions, depending on the steepness of the dose-response curves of the components."( Application of the isobologram technique for the analysis of combined effects with respect to additivity as well as independence.
Pöch, G; Reiffenstein, RJ; Unkelbach, HD, 1990
)
0.28
" No pathological findings were registered at necropsy or in microscopic observations, except an increase of liver weight at the highest dosage in the chronic study in the rat."( Toxicological evaluations of the benzodiazepine doxefazepam.
Bertoli, D; Borelli, G; Carazzone, M, 1989
)
0.28
"" Midazolam caused a shift to the left of the GABA log dose-response curve."( Modulation of GABA-gated chloride ion flux in rat brain by acute and chronic benzodiazepine administration.
Chiu, TH; Rosenberg, HC; Yu, O, 1988
)
0.27
" The GLC assay values (mean of 10 individual dosage units) for diazepam and flurazepam products were in good agreement with the results obtained by the pharmacopeial composite assays."( Routine quality evaluation of benzodiazepine drugs to USP-NF specifications.
Black, DB; Lawrence, RC; Lovering, EG; Watson, JR, 1981
)
0.49
" Such differences may be very important clinically because pharmacokinetic data will help to optimize drug therapy with respect to the choice of the proper drug and drug preparation, as well as with the choice of a proper dose and dosage regimen."( Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles.
Breimer, DD; Jochemsen, R, 1984
)
0.27
" In hamsters, 66-77% of the radioactivity was excreted within 48 hr, and 97% within 7 days of dosing (57% found in urine and 40% in feces after iv; 54% in urine and 43% in feces after po dosing)."( The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse.
Hilbert, J; Pramanik, B; Symchowicz, S; Zampaglione, N,
)
0.13
"Previous metabolic studies have established that two major metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam, are present in plasma after dosing with quazepam, a new benzodiazepine hypnotic."( Excretion of quazepam into human breast milk.
Gural, RP; Hilbert, JM; Symchowicz, S; Zampaglione, N, 1984
)
0.27
" In normal Tyrode's solution, flurazepam (1 X 10(-6), 1 X 10(-5) and 1 X 10(-4) M) noncompetitively shifted the dose-response curves for CaCl2 downwards."( Ca2+-antagonistic effects of flurazepam, a benzodiazepine derivative, on isolated guinea-pig left atria.
Akutagawa, K; Ishii, K; Makino, M, 1983
)
0.85
" Flurazepam and diazepam (1 X 10(-5), 3 X 10(-5) and 1 X 10(-4) M for coronary artery; 3 X 10(-5) and 1 X 10(-4) M for thoracic aorta) shifted the dose-response curves for KCl downwards in a non-competitive manner, and shifted the dose-response curves for CaCl2 to the right in a competitive manner."( Pharmacological effects of flurazepam and diazepam on isolated canine arteries.
Ando, J; Ishii, K; Kano, T, 1983
)
1.47
" Ten of the studies are dose-response evaluations."( Sleep spindles: pharmacological effects in humans.
Hirshkowitz, M; Karacan, I; Thornby, JI, 1982
)
0.26
" There was an approximate 10-fold shift to the right of the dose-response curve, indicating a large degree of functional tolerance after 5 weeks of FZP treatment."( Nature of functional tolerance produced by chronic flurazepam treatment in the cat.
Chiu, TH; Rosenberg, HC, 1982
)
0.52
" Dose-response analysis showed tolerance only after treatments and at times when Bmax was reduced."( Tolerance during chronic benzodiazepine treatment associated with decreased receptor binding.
Chiu, TH; Rosenberg, HC, 1981
)
0.26
" Blood samples were drawn during FLZ dosage and in the withdrawal period, and morning self-ratings of mood and sleep patterns were obtained using visual analogue scales."( Kinetics and clinical effects of flurazepam in young and elderly noninsomniacs.
Divoll, M; Greenblatt, DJ; Harmatz, JS; MacLaughlin, DS; Shader, RI, 1981
)
0.54
" Microinjection of flurazepam of the same dosage into caudal ventrolateral medulla (cVLM), however, had no depressant effect."( [Inhibitory effect of diazepam or flurazepam on pressor response induced by the stimulation of midbrain in the rabbit].
Guo, XQ; Xu, NS; Zhang, JR, 1993
)
0.89
"To evaluate the next-day residual effects of the novel hypnotic, gaboxadol, following bedtime dosing in healthy elderly subjects."( Next-day residual effects of gaboxadol and flurazepam administered at bedtime: a randomized double-blind study in healthy elderly subjects.
Boyle, J; Cerchio, K; Cummings, C; Gargano, C; Lines, C; McCrea, J; Wolford, D, 2009
)
0.62
" Intriguingly, this receptor is lacking canonical GABA binding sites but it can be activated by GABA and dose-response relationships for α1β2γ2L and α1γ2L receptors overlap."( Comparison of kinetic and pharmacological profiles of recombinant α1γ2L and α1β2γ2L GABAA receptors - A clue to the role of intersubunit interactions.
Brodzki, M; Czyzewska, MM; Jatczak, M; Kisiel, M; Mozrzymas, JW; Rutkowski, R, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
sedativeA central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
anticonvulsantA drug used to prevent seizures or reduce their severity.
GABAA receptor agonistA GABA receptor agonist specific for GABAA receptors, ligand-gated ion channels (also known as ionotropic receptors).
anxiolytic drugAnxiolytic drugs are agents that alleviate anxiety, tension, and anxiety disorders, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions.
[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 (4)

ClassDescription
1,4-benzodiazepinone
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
monofluorobenzenesAny member of the class of fluorobenzenes containing a mono- or poly-substituted benzene ring carrying a single fluorine substitutent.
tertiary amino compoundA compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
[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 (9)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
TDP1 proteinHomo sapiens (human)Potency23.87230.000811.382244.6684AID686978; AID686979
GLI family zinc finger 3Homo sapiens (human)Potency11.88320.000714.592883.7951AID1259392
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency1.54870.01237.983543.2770AID1645841
pregnane X nuclear receptorHomo sapiens (human)Potency13.72930.005428.02631,258.9301AID1346982; AID1346985
cytochrome P450 2D6Homo sapiens (human)Potency13.80290.00108.379861.1304AID1645840
aryl hydrocarbon receptorHomo sapiens (human)Potency31.67040.000723.06741,258.9301AID743085; AID743122
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency56.23410.354828.065989.1251AID504847
potassium voltage-gated channel subfamily H member 2 isoform dHomo sapiens (human)Potency3.98110.01789.637444.6684AID588834
thyroid hormone receptor beta isoform 2Rattus norvegicus (Norway rat)Potency24.41260.000323.4451159.6830AID743065; AID743067
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (107)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
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.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings 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.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
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.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
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.
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.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical 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.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID194131ED50 value was reported as log1/C, which is the concentration required to reduce locomotor activity by 50% in rats1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Rm values and structure-activity relationship of benzodiazepines.
AID679766TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: ? uM, Fluramazepam: 100 uM) in MDR1-expressing MDCKII cells2002The Journal of pharmacology and experimental therapeutics, Dec, Volume: 303, Issue:3
Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.
AID127450Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 3038 Range (42-58)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
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]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127437Tested for ability to maintain self-administration after administration of 0.03 mg/kg in monkey 2036 Range (30-36)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127316Tested for ability to maintain self-administration after administration of 0.01 mg/kg in monkey 3017 Range (14-22)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
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]
AID604743Displacement of radiolabeled warfarin from fatty acid containing human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID127314Tested for ability to maintain self-administration after administration of 0.01 mg/kg in monkey 2036 Range (25-28)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID604740Binding affinity to human serum albumin by equilibrium dialysis2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID127461Tested for ability to maintain self-administration after administration of 0.3 mg/kg in monkey 3017 Range (28-50)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127448Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 20371990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID127469Tested for ability to maintain self-administration after administration of 0.3 mg/kg in monkey 9083 Range (14-23)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID604742Displacement of radiolabeled dansylsarcosine from fatty acid-free human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID194134Halving of lever pressing in non punished rats, ED50 value reported as log 1/C1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Rm values and structure-activity relationship of benzodiazepines.
AID127464Tested for ability to maintain self-administration after administration of 0.3 mg/kg in monkey 3038 Range (12-32)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1725854Positive allosteric modulator activity at rat alpha1beta2gamma2L GABA-A receptor expressed in Xenopus laevis oocytes in presence of EC2-5 GABA by two-electrode voltage clamp assay2020ACS medicinal chemistry letters, Nov-12, Volume: 11, Issue:11
Synthesis and Biological Evaluation of Pyrroloindolines as Positive Allosteric Modulators of the α1β2γ2 GABA
AID23479Partition coefficient (logP)1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Rm values and structure-activity relationship of benzodiazepines.
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.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID127467Tested for ability to maintain self-administration after administration of 0.3 mg/kg in monkey 9079 Range (32-53)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID127449Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 3017 Range (40-47)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
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]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127451Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 9079 Range (5-20)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID227698Evaluation for the Anti-pentylenetetrazole effect.1990Journal of medicinal chemistry, Sep, Volume: 33, Issue:9
Neural networks applied to quantitative structure-activity relationship analysis.
AID604741Displacement of radiolabeled warfarin from fatty acid-free human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127445Tested for ability to maintain self-administration after administration of 0.03 mg/kg in monkey 9083 Range (19-47)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127438Tested for ability to maintain self-administration after administration of 0.03 mg/kg in monkey 2037 Range (63-73)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1472423Stability in human hepatocytes after 120 mins by HPLC-MS/MS analysis2018Journal of medicinal chemistry, 01-11, Volume: 61, Issue:1
The Magic of Crystal Structure-Based Inhibitor Optimization: Development of a Butyrylcholinesterase Inhibitor with Picomolar Affinity and in Vivo Activity.
AID127315Tested for ability to maintain self-administration after administration of 0.01 mg/kg in monkey 2037 Range (33-51)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID194132Fourfod increase in lever pressing in punished rats, ED50 value reported as log1/C1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Rm values and structure-activity relationship of benzodiazepines.
AID604744Displacement of radiolabeled dansylsarcosine from fatty acid containing human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID228469Evaluation of inclined screen test.1990Journal of medicinal chemistry, Sep, Volume: 33, Issue:9
Neural networks applied to quantitative structure-activity relationship analysis.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127453Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 9083 Range (20-32)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
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
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID127441Tested for ability to maintain self-administration after administration of 0.03 mg/kg in monkey 3017 Range (26-29)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
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]
AID127447Tested for ability to maintain self-administration after administration of 0.1 mg/kg in monkey 2036 Range (37-43)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' 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.
AID227697Compound was evaluated for the Anti-fighting behavior.1990Journal of medicinal chemistry, Sep, Volume: 33, Issue:9
Neural networks applied to quantitative structure-activity relationship analysis.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID127442Tested for ability to maintain self-administration after administration of 0.03 mg/kg in monkey 3038 Range (0-14)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' 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]
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID681116TP_TRANSPORTER: transepithelial transport (basal to apical) in MDR1-expressing MDCKII cells2002The Journal of pharmacology and experimental therapeutics, Dec, Volume: 303, Issue:3
Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.
AID127470Tested for ability to maintain self-administration after administration of 0.56 mg/kg in monkey 9079 Range (15-18)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID127456Tested for ability to maintain self-administration after administration of 0.3 mg/kg in monkey 2036 Range (10-12)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID338214Inhibition of benzodiazepine receptor at 1 nM1993Journal of natural products, Apr, Volume: 56, Issue:4
The role of receptor binding in drug discovery.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
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.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (757)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990533 (70.41)18.7374
1990's134 (17.70)18.2507
2000's53 (7.00)29.6817
2010's28 (3.70)24.3611
2020's9 (1.19)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 69.84

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

MetricThis Compound (vs All)
Research Demand Index69.84 (24.57)
Research Supply Index6.87 (2.92)
Research Growth Index4.11 (4.65)
Search Engine Demand Index124.27 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (69.84)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials160 (19.90%)5.53%
Reviews41 (5.10%)6.00%
Case Studies47 (5.85%)4.05%
Observational0 (0.00%)0.25%
Other556 (69.15%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized, Double-Blind, Placebo-Controlled, 3-Way Crossover Study to Evaluate the Effect of 2 Dosage Strengths of E2006 on a Multiple Sleep Latency Test in Subjects With Insomnia Disorder [NCT02350309]Phase 169 participants (Actual)Interventional2014-12-13Completed
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02350309 (11) [back to overview]Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo
NCT02350309 (11) [back to overview]Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo
NCT02350309 (11) [back to overview]Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment
NCT02350309 (11) [back to overview]Number of Participants With Clinically Significant Abnormal Laboratory Values
NCT02350309 (11) [back to overview]Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
NCT02350309 (11) [back to overview]Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters
NCT02350309 (11) [back to overview]Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT
NCT02350309 (11) [back to overview]Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3
NCT02350309 (11) [back to overview]Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4
NCT02350309 (11) [back to overview]Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT
NCT02350309 (11) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation

Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL. (NCT02350309)
Timeframe: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)

InterventionParticipants (Count of Participants)
Lemborexant 5 mg4
Lemborexant 10 mg13
Flurazepam 30 mg25

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Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL. (NCT02350309)
Timeframe: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)

InterventionParticipants (Count of Participants)
Lemborexant 5 mg9
Lemborexant 10 mg20
Flurazepam 30 mg35

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Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL. (NCT02350309)
Timeframe: Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks)

InterventionParticipants (Count of Participants)
Lemborexant-matched Placebo3
Lemborexant 5 mg11
Lemborexant 10 mg20
Flurazepam 30 mg36

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Number of Participants With Clinically Significant Abnormal Laboratory Values

(NCT02350309)
Timeframe: From first dose of study drug up to Day 54

InterventionParticipants (Count of Participants)
Lemborexant-matched Placebo0
Lemborexant 5 mg0
Lemborexant 10 mg0
Flurazepam 30 mg0

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Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values

(NCT02350309)
Timeframe: From first dose of study drug up to Day 54

InterventionParticipants (Count of Participants)
Lemborexant-matched Placebo0
Lemborexant 5 mg0
Lemborexant 10 mg0
Flurazepam 30 mg0

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Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters

(NCT02350309)
Timeframe: From first dose of study drug up to Day 54

InterventionParticipants (Count of Participants)
Lemborexant-matched Placebo0
Lemborexant 5 mg0
Lemborexant 10 mg0
Flurazepam 30 mg0

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Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT

Pearson correlation was used to calculate the relationship between PK concentration of lemborexant and sleepiness. The M-MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. (NCT02350309)
Timeframe: Baseline up to Day 44 (Week 6)

Interventioncorrelation coefficient (Number)
Lemborexant 5 or 10 mg: All Participants-0.2746

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Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The multiple sleep latency test (MSLT) is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four Sleep Latency Tests (SLTs), with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL. (NCT02350309)
Timeframe: Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks)

,,
Interventionminutes (Mean)
BaselineChange at Day 2 After Each Treatment
Lemborexant 10 mg18.25-6.95
Lemborexant 5 mg18.28-4.56
Lemborexant-matched Placebo18.25-3.43

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Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL. (NCT02350309)
Timeframe: Baseline, Day 2 of Treatment Period 4 (Week 6)

Interventionminutes (Mean)
BaselineChange at Day 2 of Treatment Period 4
Flurazepam 30 mg18.25-9.49

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Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT

The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. (NCT02350309)
Timeframe: Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)

,
Interventionnanogram per milliliter (ng/mL) (Mean)
Lemborexant: Day 2Metabolite M10: Day 2Lemborexant: Day 16Metabolite M10: Day 16Lemborexant: Day 30Metabolite M10: Day 30
Lemborexant 10 mg6.4232.5825.3062.6895.2932.304
Lemborexant 5 mg2.2851.2463.2361.3612.0200.994

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Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation

(NCT02350309)
Timeframe: From first dose of study drug up to Day 54

,,,
InterventionParticipants (Count of Participants)
TEAEsSAEsAEs Leading to DeathAEs Leading to Discontinuation
Flurazepam 30 mg5000
Lemborexant 10 mg8000
Lemborexant 5 mg5000
Lemborexant-matched Placebo2000

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