Inhibitors of cytochrome P450 differentially modify discriminative-stimulus and antinociceptive effects of hydrocodone and hydromorphone in rhesus monkeys

Snjezana Lelas, Sandra Wegert, S. Victoria Otton, Edward M. Sellers, Charles P. France

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The present study was conducted to investigate the role of cytochrome P450 in the discriminative-stimulus and antinociceptive effects of hydrocodone (HC) and hydromorphone (HM) in rhesus monkeys. In morphine-deprived monkeys, morphine dose-dependently reversed naltrexone-lever responding, an effect also produced by HC and HM. HC and HM also produced antinociception in a warm-water tail withdrawal procedure. Budipine and naltrexone shifted the dose-effect curves for the discriminative-stimulus effects of HC and HM to the right. In contrast, naltrexone, but not budipine (10.0 mg/kg) or quinidine (10.0 mg/kg), dose-dependently antagonized the antinociceptive effects of HC. Budipine and quinidine decreased the concentration of HM in plasma without significantly affecting the levels of HC, suggesting that these CYP2D6 inhibitors decreased the conversion of HC-HM. Thus, some behavioral effects of HC are not modified by a marked inhibition of CYP2D6, suggesting that these effects of HC are not due to its conversion to HM but, rather, that both HC and HM act directly on μ receptors. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalDrug and Alcohol Dependence
Volume54
Issue number3
DOIs
StatePublished - May 3 1999
Externally publishedYes

Keywords

  • Antinociception
  • Drug discrimination
  • Hydrocodone
  • P450 enzymes
  • Rhesus monkey

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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