Zaleplon and triazolam: drug discrimination, plasma levels, and self-administration in baboons.
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.
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Behavioral Biology Research Center, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, John Hopkins Bayview Campus, 5510 Nathan Shock Drive Ste 3000, Baltimore, MD, 21224-6823, USA. ator@mail.jhmi.edu
D000081:Acetamides / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D010215:Papio; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D012646:Self Administration; D014229:Triazolam / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*
D000081:Acetamides; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; D014229:Triazolam; C085665:zaleplon