Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons

Research output: Contribution to journalArticle

Abstract

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. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)69-84
Number of pages16
JournalDrug and Alcohol Dependence
Volume61
Issue number1
DOIs
StatePublished - Dec 22 2000

Fingerprint

zaleplon
Triazolam
Papio
drug
Benzodiazepines
withdrawal
Pharmaceutical Preparations
Flumazenil
GABA-A Receptors
Ataxia
Hypnotics and Sedatives
Drug delivery
food
Plasmas
Food
ability

Keywords

  • Abuse potential
  • Benzodiazepine
  • CL 284 846
  • Dependence
  • Feeding
  • Triazolam
  • Zaleplon

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

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title = "Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons",
abstract = "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. (C) 2000 Elsevier Science Ireland Ltd.",
keywords = "Abuse potential, Benzodiazepine, CL 284 846, Dependence, Feeding, Triazolam, Zaleplon",
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AU - Ator, Nancy A

AU - Weerts, Elise

AU - Kaminski, Barbara J.

AU - Kautz, Mary A.

AU - Griffiths, Roland R

PY - 2000/12/22

Y1 - 2000/12/22

N2 - 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. (C) 2000 Elsevier Science Ireland Ltd.

AB - 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. (C) 2000 Elsevier Science Ireland Ltd.

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