Differential effects in humans after repeated administrations of zolpidem and triazolam

Zolpidem, a commonly prescribed hypnotic, is an imidazopyridine that purportedly has a unique benzodiazepine-receptor binding profile. Despite its unique binding profile, human laboratory experiments have generally failed to demonstrate meaningful behavioral pharmacological differences between zolpidem and classic benzodiazepine-receptor agonists like triazolam. In this article, two groups of nondrug-abusing volunteers received 15 mg zolpidem (N = 11) or 0.375 mg zolpidem (N = 15) on four separate occasions and placebo on two other occasions. In both groups, the order of drug administration was quasirandom. Drug effects were assessed with a battery of laboratory performance tasks and subject-rated drug-effect questionnaires. Zolpidem and triazolam produced prototypical sedative-like effects (e.g., impaired performance, increased subject-ratings of sedation). The performance-impairing effects of triazolam, but not zolpidem, were significantly less after the final administration relative to the initial administration. The subject-rated effects of both zolpidem and triazolam were significantly less after the final administration relative to the initial administration. The results of this experiment suggest that zolpidem and triazolam differ in terms of tolerance-producing effects. Future studies should assess the tolerance-producing effects of zolpidem across a range of doses, as well as other novel sedatives such as zaleplon.