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.
Oliveto
Alison
A
CT and VA Connecticut Healthcare System, Yale University, New Haven, 950 Campbell Avenue, Psychiatry 116A-4, Building 36, West Haven, CT 06516, USA. alison.oliveto@yale.edu
Poling
James
J
Kosten
Thomas R
TR
Gonsai
Kishorchandra
K
D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003915:Dextromethorphan / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000523:psychology
D009270:Naloxone; D003915:Dextromethorphan; D008691:Methadone; D017275:Isradipine