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.
Hustveit
O
O
Department of Pharmacology, University of Oslo, Norway.
Setekleiv
J
J
D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000008:administration & dosage / Q000494:pharmacology*; D009116:Muscarine / Q000037:antagonists & inhibitors; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects
D018727:Muscarinic Antagonists; D009116:Muscarine; D002217:Carbachol; D008614:Meperidine; D005283:Fentanyl