Na. Ator et al., Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons, DRUG AL DEP, 61(1), 2000, pp. 69-84
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 g
iven to baboons by intragastric infusion once each day, with doses increasi
ng every 17 days. Next, the highest dose was given for 10-34 additional day
s by continuous infusion. Both drugs produced increases in food-maintained
lever pressing, ataxia, and time to complete a fine motor task. Plasma leve
ls increased dose-dependently; drug was detectable 24 h after higher doses.
Flumazenil produced a mild or intermediate precipitated-withdrawal syndrom
e on day 14 of all dosing conditions. When drug delivery ended after 85-100
days, a benzodiazepine-type withdrawal syndrome occurred. Physical depende
nce potential of zaleplon and triazolam appear similar. (C) 2000 Elsevier S
cience Ireland Ltd. All rights reserved.