Quazepam

Effects

Overview

Benzodiazepine derivate drug, noral is prescribed for short term treatment of insomnia, and sleep maintenance. its MOA is very similar to Ambien and Sonata and substitutes for those in animal studies. TS

Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively (and uniquely) selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines (due to its novel receptor-subtype selectivity). Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.[1–5] WP

It was patented in 1970 and came into medical use in 1985.[6] WP

History

Legal status

Pharmacology

Pharmacology

Quazepam is a trifluoroalkyl type of benzodiazepine. Quazepam is unique amongst benzodiazepines in that it selectively targets the GABAA α₁ subunit receptors, which are responsible for inducing sleep. Its mechanism of action is very similar to zolpidem and zaleplon in its pharmacology and can successfully substitute for zolpidem and zaleplon in animal studies.[7][8][9] WP

Quazepam is selective for type 1 benzodiazepine receptors containing the α₁ subunit, similar to other drugs such as zaleplon and zolpidem. As a result, quazepam has little or no muscle-relaxant properties. Most other benzodiazepines are unselective and bind to type1 GABAA receptors and type2 GABAA receptors. Type1 GABAA receptors include the α₁ subunit containing GABAA receptors, which are responsible for the hypnotic properties of the drug. Type 2 receptors include the α₂, α₃ and α₅ subunits, which are responsible for anxiolytic action, amnesia, and muscle relaxant properties. Thus, quazepam may have less side effects than other benzodiazepines, but, it has a very long half-life of 25 hours, which reduces its benefits as a hypnotic due to likely next day sedation. It also has two active metabolites with half-lives of 28 and 79 hours. Quazepam may also cause less drug tolerance than other benzodiazepines such as temazepam and triazolam, perhaps due to its subtype selectivity. The longer half-life of quazepam may have the advantage, however, of causing less rebound insomnia than shorter-acting subtype selective nonbenzodiazepines. However, one of the major metabolites of quazepam, the N-desmethyl-2-oxoquazepam (N-desalkylflurazepam), binds unselectively to both type 1 and type 2 GABAA receptors. The N-desmethyl-2-oxoquazepam metabolite also has a very long half-life and likely contributes to the pharmacological effects of quazepam.[10–18] WP

Pharmacokinetics

Quazepam has an absorption half-life of 0.4 hours with a peak in plasma levels after 1.75 hours. It is eliminated both renally and through feces. The active metabolites of quazepam are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. The N-desalkyl-2-oxoquazepam metabolite has only limited pharmacological activity compared to the parent compound quazepam and the active metabolite 2-oxoquazepam. Quazepam and its major active metabolite 2-oxoquazepam both show high selectivity for the type1 GABAA receptors. The elimination half-life range of quazepam is between 27 and 41 hours.[19–24] WP⚠ Wikipedia itself has flagged this text: citation needed.

Mechanism of action

Quazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor. This modulation enhances the actions of GABA, causing an increase in the opening frequency of the chloride ion channel, which results in an increased influx of chloride ions into the GABAA receptors. Quazepam, unique amongst benzodiazepine drugs, selectively targets type 1 benzodiazepine receptors, which results in reduced sleep latency and promotion of sleep. Quazepam also has some anticonvulsant properties.[25–28] WP

Chemistry

Formula

C17H11ClF4N2S PC

CAS number

36735-22-5 PC

Molar mass (g/mol)

386.8 PC

IUPAC name (computed by PubChem)

7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine-2-thione PC

SMILES

C1C(=S)N(C2=C(C=C(C=C2)Cl)C(=N1)C3=CC=CC=C3F)CC(F)(F)F PC

InChIKey

IKMPWMZBZSAONZ-UHFFFAOYSA-N PC

PubChem CID

4999

IUPAC name

7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine-2-thione WP

Pop culture

No references added yet.

References

1. Other US Patent 3845039
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6. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
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