Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition
site on the GABA
A benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ
1 (ω
1) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing
effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories
of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this
double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect
questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including
balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and
next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also
suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study
was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect,
and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique
benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam.
Key words Zaleplon - Triazolam - Benzodiazepine - Hypnotics - Learning - Memory - Abuse potential - Human
Received: 14 April 1998/Final version: 13 January 1999