Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes.
The affinity of a number of 'selective' agonists and antagonists has been assessed at atrial or ileal muscarinic receptors by use of in vitro functional analysis. The most selective compound for ileal muscarinic receptors was silabenzhexol (approx. 50 fold), and to a lesser extent benzhexol (approx. 5 fold). Conversely, the most selective compound for the atrial muscarinic receptors was AF-DX 116 (approx. 6 fold). The novel M1-receptor antagonist, telenzepine and other antagonists such as propantheline and isopropamide did not distinguish between atrial and ileal receptors. Dicyclomine, adiphenine, hexahydroadiphenine and oxyphenonium exhibited competitive antagonism at atrial receptors but non-competitive antagonism at ileal receptors. No conclusions could, therefore, be drawn with regard to their selectivity. The agonists, arecaidine propargyl ester (APE), ethoxyethyltriethylammonium (EOE) and carbachol, exhibited some selectivity in potency but little difference in affinity. It is concluded that the study supports the existence of ileal and atrial muscarinic receptor subtypes. However, the use of dicyclomine and related compounds in receptor classification is limited.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D002217:Carbachol