Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons.
The ability of the GABA(A)-receptor-subtype-selective hypnotic zaleplon to produce physical dependence was compared to the nonselective benzodiazepine triazolam. Progressively increasing doses of zaleplon and triazolam were given to baboons by intragastric infusion once each day, with doses increasing every 17 days. Next, the highest dose was given for 10-34 additional days by continuous infusion. Both drugs produced increases in food-maintained lever pressing, ataxia, and time to complete a fine motor task. Plasma levels increased dose-dependently; drug was detectable 24 h after higher doses. Flumazenil produced a mild or intermediate precipitated-withdrawal syndrome on day 14 of all dosing conditions. When drug delivery ended after 85-100 days, a benzodiazepine-type withdrawal syndrome occurred. Physical dependence potential of zaleplon and triazolam appear similar.
Ator
N A
NA
Behavioral Biology Research Center, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Ste. 3000, 5510 Nathan Shock Drive, John Hopkins Bayview Campus, Baltimore, MD 21224-6823, USA. ator@mail.jhmi.edu
Weerts
E M
EM
Kaminski
B J
BJ
Kautz
M A
MA
Griffiths
R R
RR
D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; 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; D011597:Psychomotor Performance / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000097:blood*; D013997:Time Factors; D014229:Triazolam / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000081:Acetamides; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; D014229:Triazolam; C085665:zaleplon