[Involvement of opiate receptors in the mode of action of trimebutine].

Several studies in dogs, cats, rabbits and humans have suggested that the motility stimulating properties of trimebutine (TMB) are mediated by peripheral opiate receptors. The present work deals with the capacity of TMB and its N-desmethyl metabolite (NDTMB) to displace mu, delta and kappa specific ligands from their receptors using guinea-pig brain membranes and ileal myenteric plexus synaptosomal membrane preparations. The activity of both compounds on the twitch response induced by transmural stimulation on the guinea-pig ileum as well as the mouse and rabbit vas deferens was also investigated. These preparations have been proposed to be specific for the mu, delta and kappa receptor subtypes respectively. TMB (0.2 to 1.8 microM) and NDTMB (0.3 to 6 microM) displayed a good affinity for all receptor subtypes in brain and myenteric plexus preparations. Both compounds also inhibited the twitch response of all three isolated organ preparations. The decreasing order of IC50's of TMB ranged from 0.75 microM in the guinea-pig ileum to 7.1 and 39 microM in the vas deferens of the rabbit and the mouse respectively. These results indicate that TMB and NDTMB possess mu, delta as well as kappa agonist properties without true specificity for one or the other of these subtypes. They also confirm that activation of peripheral mu, delta and kappa opiate receptors mediate the gastrointestinal motility effect of TMB.