Benzodiazepine-Receptor Ligands in Humans

The study presented here compared the acute performance-impairing, subject-rated, and observer-rated effects of quazepam (15, 30, and 45 mg), triazolam (0.1875, 0.375, and 0.5625 mg), zolpidem (7.5, 15, and 22.5 mg), and placebo in nine healthy, non-drug-abusing humans. Quazepam, a trifluoroethylbenzodiazepine, was chosen for study because, when compared with triazolam, a triazolobenzodiazepine, it is a relatively weak benzodiazepine-receptor ligand, and it may bind selectively to the BZ1 benzodiazepine-receptor subtype. Zolpidem, an imidazopyridine, is the most commonly prescribed hypnotic and was chosen for study because it is biochemically distinct from benzodiazepine hypnotics and also purportedly binds selectively to the BZ1 benzodiazepine-receptor subtype. Triazolam was chosen as the reference compound because it binds nonselectively to BZ1 and BZ2 benzodiazepine-receptor subtypes. Triazolam, zolpidem, quazepam, and placebo were administered orally in a double-blind, crossover design. Triazolam and zolpidem produced orderly dose- and time-related impairment of learning, performance, and recall, and produced sedative-like subject- and observer-rated drug effects. The behavioral pharmacologic profile of zolpidem and triazolam was indistinguishable in that at peak effect, the absolute magnitude of drug effect was comparable across the various measures. Quazepam, by contrast, did not impair performance on any task to a statistically significant degree, nor did it produce significant sedation as measured by subject- and observer-rated drug-effect questionnaires. Whether these effects are a result of the unique benzodiazepine-receptor binding profile of quazepam or the testing of insufficient dosages is unknown. Future research could extend the findings presented here by testing higher dosages of quazepam.