MUSCARINIC M(1) AND M(3) RECEPTOR ANTAGONIST EFFECTS OF A NEW PIRENZEPINE ANALOG IN ISOLATED GUINEA-PIG ILEAL LONGITUDINAL MUSCLE-MYENTERICPLEXUS

The new pirenzepine analogue DF 545 has been tested for its muscarinic M(1) and M(3) receptor antagonist properties in guinea-pig longitudin al muscle-myenteric plexus preparations. McN-A-343-induced inhibition of twitch contractions was taken as a parameter for muscarinic M(1) re ceptor activation while electrical and acetylcholine-induced contracti ons were considered as a model for muscarinic M(3) receptor stimulatio n. An unexpected contractile effect evoked by McN-A-343 was also inves tigated. In contrast to pirenzepine, DF 545 only weakly counteracted t he M(1)-mediated McN-A-343 inhibitory effect but blocked M(3)-related twitch- or acetylcholine-stimulated responses with a 2-fold higher aff inity than pirenzepine. Therefore, in this preparation, our findings s uggest that DF 545 does not share the selectivity profile exhibited by pirenzepine at ileal muscarinic receptors. Studies on the McN-A-343 c ontractile effect provide evidence that this agonist may interact with ileal muscarinic effector sites in a different way from other choline rgic agents.