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

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.