Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers

Zolpidem is an imidazopyridine hypnotic that is biochemically distinct from classic benzodiazepine agonists in that it may be selective for the BZ1 receptor subtype and shows a different pattern of distribution of binding sites. The present study compared the learning, recall, performance, subject-rated and observer-rated effects of zolpidem, triazolam, and temazepam in 11 healthy humans. Placebo, zolpidem (5, 10, and 20 mg/70 kg), triazolam (0.125, 0.25, and 0.50 mg/70 kg), and temazepam (15, 30, and 60 mg/70 kg) were administered orally in a randomized, double-blind, cross-over design. Zolpidem, triazolam, and temazepam produced orderly dose- and time-related impairment of learning, recall, and performance, and increased subject- and observer-rated estimates of strength of drug effect. The absolute magnitude of these effects at peak effect were comparable across the three compounds. The time to maximal drug effect was faster with zolpidem (0.5-1.0 hours) than with triazolam (1.5-2.0 hours) or temazepam (2-3 hours). These results suggest that despite the somewhat unique benzodiazepine receptor-binding profile of zolpidem, its behavioral and subject-rated effects are similar to those of benzodiazepine hypnotics (i.e., triazolam and temazepam).