Isradipine and dextromethorphan in methadone-maintained humans under a naloxone discrimination procedure

Eur J Pharmacol. 2004 May 3;491(2-3):157-68. doi: 10.1016/j.ejphar.2004.03.024.

Abstract

In seven methadone-maintained human participants trained to distinguish between a low dose of naloxone (0.15 mg/70 kg, i.m.; i.e., Drug A) and placebo (i.e., Drug B) under an instructed novel-response drug discrimination procedure, the calcium channel blocker isradipine (0-10 mg/70 kg, p.o.; N=7) and the N-methyl-D-aspartic acid (NMDA) receptor antagonist dextromethorphan (0-60 mg/70 kg, p.o.; N=6) were tested each alone and in combination with the training dose of naloxone. Isradipine alone produced some naloxone- and novel-appropriate responding, minimal changes in self-reports and decreases in blood pressure. Dextromethorphan alone produced some novel-appropriate responding and minimal changes in self-reports and vital signs. When combined with naloxone, isradipine significantly attenuated naloxone-occasioned responding, without increasing novel-appropriate responding, and attenuated naloxone-induced increases in opioid receptor antagonist ratings and ratings measuring sedation. Dextromethorphan significantly attenuated naloxone-appropriate responding, increased novel-appropriate responding, and enhanced naloxone's effects on ratings of dysphoric effects. These results suggest that isradipine attenuates and dextromethorphan enhances some of the behavioral effects of naloxone in opioid-dependent humans.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Dextromethorphan / pharmacology*
  • Discrimination Learning / drug effects*
  • Discrimination Learning / physiology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Isradipine / pharmacology*
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Naloxone / pharmacology*
  • Opioid-Related Disorders / drug therapy
  • Opioid-Related Disorders / psychology

Substances

  • Naloxone
  • Dextromethorphan
  • Methadone
  • Isradipine