Zaleplon and triazolam in humans: acute behavioral effects and abuse potential

Psychopharmacology (Berl). 1999 Jul;145(1):39-51. doi: 10.1007/s002130051030.


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 BZ1 (omega1) 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetamides / pharmacokinetics*
  • Adolescent
  • Adult
  • Behavior / drug effects*
  • Behavior, Addictive / psychology
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics*
  • Illicit Drugs / pharmacokinetics*
  • Male
  • Observer Variation
  • Pyrimidines / pharmacokinetics*
  • Triazolam / pharmacokinetics*


  • Acetamides
  • Hypnotics and Sedatives
  • Illicit Drugs
  • Pyrimidines
  • Triazolam
  • zaleplon