Behavioral pharmacology of zolpidem relative to benzodiazepines: a review

Zolpidem, an imidazopyridine that purportedly binds selectively to certain GABA(A) receptor subtypes, is the most commonly prescribed hypnotic. The present article critically reviewed the extant experimental literature to determine whether the behavioral pharmacologic profile of zolpidem also differs from that of benzodiazepines. Specific topics that are reviewed include: 1) reinforcing effects and abuse potential, 2) discriminative-stimulus effects, 3) subject-rated drug effects, 4) performance-impairing effects, 5) tolerance-producing effects, and 6) physiological dependence-producing effects. Studies that employed both nonhumans and humans are reviewed. Based on the available literature, the most parsimonious conclusion is that despite its unique neuropharmacological profile, the behavioral effects of zolpidem are generally similar to those of benzodiazepines. However, it is important to note the dearth of perspective, experimental studies that directly compared zolpidem and a benzodiazepine. Because of the clinical relevance and paucity of published studies, future research should focus explicitly on assessing the reinforcing effects, abuse potential, performance-impairing effects, tolerance-producing effects, and dependence-producing effects of zolpidem relative to a benzodiazepine. Important issues such as the selection of an appropriate comparison drug and subject population, and the doses tested needed to be considered in these future studies.