Zaleplon and triazolam: drug discrimination, plasma levels, and self-administration in baboons

Drug Alcohol Depend. 2000 Dec 22;61(1):55-68. doi: 10.1016/s0376-8716(00)00123-x.

Abstract

Zaleplon is a chemically novel hypnotic that preferentially binds alpha(1)-subunit containing subtypes of the alphabetagamma configuration of the gamma-aminobutyric acid (GABA)(A) receptor. Zaleplon and the non-subtype-selective hypnotic triazolam occasioned 100% drug-appropriate responding in baboons trained to discriminate lorazepam or pentobarbital from vehicle. Flumazenil shifted the zaleplon generalization gradient at least five-fold to the right. A plasma elimination half-life of 6-8 h for oral 10 mg/kg zaleplon and 0.32 mg/kg triazolam was paralleled by discriminative control for 7 h. Zaleplon maintained self-injection greater than vehicle, as did comparison doses of the similarly selective hypnotic zolpidem and triazolam. Concurrent food-maintained responding increased during self-injection of all three drugs. Preferential binding at this alpha(1)-containing GABA(A) subtype did not diminish the benzodiazepine (Bzs)-like behavioral effects of zaleplon.

Publication types

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

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / blood*
  • Acetamides / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Discrimination Learning / drug effects*
  • Dose-Response Relationship, Drug
  • GABA Modulators / administration & dosage
  • GABA Modulators / blood*
  • GABA Modulators / pharmacology*
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / blood*
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Papio
  • Pyrimidines / administration & dosage
  • Pyrimidines / blood*
  • Pyrimidines / pharmacology*
  • Self Administration
  • Triazolam / administration & dosage
  • Triazolam / blood*
  • Triazolam / pharmacology*

Substances

  • Acetamides
  • GABA Modulators
  • Hypnotics and Sedatives
  • Pyrimidines
  • Triazolam
  • zaleplon