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

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Abstract
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. 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. 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. 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.