Muscarinic M1 and M3 receptor antagonist effects of a new pirenzepine analogue in isolated guinea-pig ileal longitudinal muscle-myenteric plexus.
The new pirenzepine analogue DF 545 has been tested for its muscarinic M1 and M3 receptor antagonist properties in guinea-pig longitudinal muscle-myenteric plexus preparations. McN-A-343-induced inhibition of twitch contractions was taken as a parameter for muscarinic M1 receptor activation while electrical and acetylcholine-induced contractions were considered as a model for muscarinic M3 receptor stimulation. An unexpected contractile effect evoked by McN-A-343 was also investigated. In contrast to pirenzepine, DF 545 only weakly counteracted the M1-mediated McN-A-343 inhibitory effect but blocked M3-related twitch- or acetylcholine-stimulated responses with a 2-fold higher affinity than pirenzepine. Therefore, in this preparation, our findings suggest that DF 545 does not share the selectivity profile exhibited by pirenzepine at ileal muscarinic receptors. Studies on the McN-A-343 contractile effect provide evidence that this agonist may interact with ileal muscarinic effector sites in a different way from other cholinergic agents.
Barocelli
E
E
Institute of Pharmacology and Pharmacognosy, University of Parma, Italy.
Ballabeni
V
V
Chiavarini
M
M
Molina
E
E
Lavezzo
A
A
Impicciatore
M
M
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects
D001570:Benzodiazepinones; D018727:Muscarinic Antagonists; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; C064721:nuvenzepine; D000109:Acetylcholine