Dose-dependent and stereoselective antagonism by diltiazem of naloxone-precipitated morphine abstinence after acute morphine-dependence in vivo and in vitro.
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.
Caro
G
G
Department of Pharmacology, Granada University School of Medicine, Spain.
Barrios
M
M
Baeyens
J M
JM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009021:Morphine Dependence / Q000188:drug therapy / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D009270:Naloxone; D004110:Diltiazem