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

Zaleplon is a chemically novel hypnotic that preferentially binds α₁-subunit containing subtypes of the αβγ configuration of the γ-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 α₁-containing GABA(A) subtype did not diminish the benzodiazepine (Bzs)-like behavioral effects of zaleplon. (C) 2000 Elsevier Science Ireland Ltd.