Dose-dependent and stereoselective antagonism by diltiazem of naloxone-precipitated morphine abstinence after acute morphine-dependence in vivo and in vitro

Abstract

The effects of two enantiomers of diltiazem (l-cis and d-cis) on naloxone-precipitated morphine abstinence after acute morphine dependence were evaluated in vivo in mice and in vitro in isolated pieces of rat terminal ileum. d-cis-diltiazem (10-40 mg/kg) produced a dose-dependent inhibition of the jumping and body weight loss induced by naloxone in acutely morphine dependent mice. By contrast, l-cis-diltiazem 40 mg/kg did not significantly inhibit jumping and produced a much lower inhibition of body weight loss than the same dose of d-cis-diltiazem. In addition, d-cis-diltiazem (0.01-1 microM) produced a concentration-dependent inhibition of naloxone-induced contracture in morphine dependent ilea, whereas l-cis-diltiazem, even at 1 microM, did not inhibit this contracture. These results suggest that calcium channels may play a similar role in naloxone-precipitated morphine abstinence in vivo and in vitro.