Effect of clonidine, nimodipine and diltiazem on the in vitro opioid withdrawal response in the guinea-pig ileum

Abstract

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 μM), diltiazem (0.25, 0.5 and 1 μM) or nimodipine (0.05, 0.1 and 1 μM) 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 α2-adrenoceptor agonists, all of the drugs tested prevented the contracture induced by naloxone in morphine-dependent guinea-pig ileum.