Effect of clonidine, nimodipine and diltiazem on the in vitro opioid withdrawal response in the guinea-pig ileum.
1. The effects of clonidine, nimodipine and diltiazem, on the in vitro withdrawal contracture induced by naloxone in the guinea-pig ileum obtained from morphine-dependent animals, were evaluated. 2. The in vitro incubation with clonidine (0.01, 0.1 and 1 microM), diltiazem (0.25, 0.1 and 1 microns) or nimodipine (0.05, 0.1 and 1 microns) reduced significantly the force of the contracture induced by naloxone in the morphine-dependent guinea-pig ileum. 3. The intraperitoneal administration of clonidine (0.3 mg kg-1), nimodipine (5 mg kg-1) or diltiazem (20 mg kg-1) reduced the contractile response induced by naloxone in the morphine-dependent guinea-pig ileum. 4. It is concluded that at least part of the effect of clonidine, nimodipine and diltiazem on withdrawal contractures is mediated via a peripheral, rather than a central site of action. Even though, the mechanism responsible for the effect of the calcium channel blockers differs from that of alpha 2-adrenoceptor agonists, all of the drugs tested prevented the contracture induced by naloxone in morphine-dependent guinea-pig ileum.
Alfaro
M J
MJ
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Colado
M I
MI
López
F
F
Martín
M I
MI
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009021:Morphine Dependence / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D009270:Naloxone; D009553:Nimodipine; D004110:Diltiazem; D003000:Clonidine