Interaction Between Opioid And Muscarinic Receptors In The Guinea-Pig Ileum Preparation: A Mathematical Model

Fentanyl and pethidine are opioid agonists and muscarinic antagonists in the guinea-pig ileum preparation. In this preparation an opioid agonist reduces the release of acetylcholine. Therefore an opiate may influence the potency of an anticholinergic drug. A mathematical model was developed to characterize this putative interaction between opioid and muscarinic receptors. The model is based on the assumption that the drugs interact with the receptors in a competitive manner according to the law-of-mass action. Concentration-response experiments were performed in the guinea-pig ileum preparation to test the model. The mathematical model describes the concentration-response curves very well and estimates the IC50 values for the two components with good precision. The study shows that an opioid agonist can potentiate the effect of an anticholinergic drug substantially. This is interesting with regard to the central anticholinergic syndrome. The conclusion is that the model describes the interaction adequately.