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 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.