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Acute tolerance to diazepam in cats and its possible relationship to diazepam metabolism

Authors
Journal
European Journal of Pharmacology
0014-2999
Publisher
Elsevier
Publication Date
Volume
13
Issue
2
Identifiers
DOI: 10.1016/0014-2999(71)90155-5
Keywords
  • Acute Tolerance To Diazepam In Cats
  • N-Desmethyl Diazepam
  • Oxazepam
  • Diazepam And Linguomandibular Reflex
  • 3-Hydroxy Diazepam
  • Linguomandibular Reflex

Abstract

Abstract The depressant effects on the linguomandibular reflex (LMR) of diazepam was studied in allobarbital-urethane anesthetized cats. Tolerance to either i.v. or i.d. administration was evidenced by a progressive decrease in response to increasing doses of diazepam. Tolerance resulted only when the interval between doses was greater than 15 min, suggesting that it might be related to metabolite formation. N-Desmethyl diazepam, the major metabolite of diazepam in most species, produced dose-related inhibition of the LMR and was 0.2 as potent as diazepam. Simultaneous administration of N-desmethyl diazepam with increasing doses of diazepam produced less inhibition of the LMR than diazepam alone. These results indicate that tolerance occurs after acute administration of diazepam, and suggests that metabolite(s) of diazepam may be responsible for this effect.

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