Fentanyl and pethidine are antagonists on muscarinic receptors in guinea-pig ileum.

In order to evaluate the anticholinergic effect of fentanyl and pethidine, the influence of these drugs on the cumulative dose-response curves of carbacholine on the guinea-pig ileum has been investigated. Fentanyl and pethidine displaced the dose-response curve for carbacholine to the right in a parallel fashion, indicating competitive antagonism. Dissociation constants determined by an agonist EC versus antagonist plot were 0.22 mumol/l for fentanyl and 1.4 mumol/l for pethidine. It is concluded that during high-dose fentanyl anaesthesia, fentanyl may bind to muscarinic receptors and thereby produce a central anticholinergic syndrome. An additional finding was that the maximal response to carbacholine increased significantly when combined with pethidine.