Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes

We examined the behavioral pharmacological properties of six benzodiazepine (ω) receptor ligands including brotizoram, nitrazepam, quazepam, rilmazafone, zolpidem and zopiclone and the binding of these drugs with ω receptor subtypes. Behavioral tests were performed at the time of the maximal effects induced by each drug following its oral administration to mice. All of these drugs dose-dependently induced impairment of motor coordination as rotarod performance and potentiation of thiopental-induced anesthesia as hypnotic effect. The hypnotic effects of rilmazafone, whose major metabolites were bound to both ω₁ and ω₂ receptors with high affinity, and ω₁ selective quazepam were about 20 times more effective than the induction of motor impairments when compared with ED ₅₀ values. However, there was no difference between the ED ₅₀ values of ω₁ selective zolpidem alone in these two tests. An antianxiety efficacy of zolpidem was relatively weak unlike that of other drugs in the elevated plus-maze. It has been reported that ω₁, but not ω₁, receptors are associated with motor impairment and anxiolytic effect. The weak anxiolytic effect of zolpidem supports the previous hypothesis. However, the strong motor incoordination of zolpidem suggests that not only ω₂ but also ω₁ receptors are related to motor impairment unlike the previous hypothesis.