Quazepam

Quazepam exerts its hypnotic effects through positive allosteric modulation of gamma-aminobutyric acid type A (GABA-A) receptors in the central nervous system. Unlike classical benzodiazepines, quazepam demonstrates unique pharmacological selectivity for sleep-promoting α1 subunit-containing GABA-A receptors, which distinguishes it from other hypnotic agents. This selectivity likely contributes to the decreased rate of adverse events observed clinically, including tolerance, rebound insomnia and amnesic behaviours. Quazepam binds to the interface between α and γ subunits on the GABA-A receptor complex, commonly referred to as the benzodiazepine binding site. Upon binding, it enhances the receptor's response to GABA, increasing chloride channel opening frequency and potentiating inhibitory neurotransmission. The drug exhibits a significantly lower relative receptor binding affinity compared to other benzodiazepines, which may explain its favourable side effect profile.

Fig. 1 Metabolic pathway of Quazepam leading to its active metabolites 2-oxoquazepam and N-desalkyl-2-oxoquazepam. (Moniri N H. 2019)