Himbacine discriminates between putative muscarinic M1 receptor-mediated responses.
This study describes the antagonistic properties of himbacine, in comparison with those of pirenzepine, at muscarinic receptors mediating the depolarization of rat superior cervical ganglion, the inhibition of electrically-induced twitch contractions of rabbit vas deferens and the contraction of dog saphenous vein, currently classified as putative muscarinic M1 sites. The affinity of himbacine for the vas deferens site (pA2 8.08) was nearly ten times higher than those for the M1 receptors of rat ganglion and dog saphenous vein (pA2 7.14 and 7.16, respectively); affinity estimates for pirenzepine were similar throughout the different preparations. The present data are consistent with the allocation of ganglion and saphenous vein receptors into the M1 subclass; the profile of the vas deferens site, conversely, appears to be different, and possibly more closely related to that reported for the M4/m4 receptor.
Sagrada
A
A
Dept. of Pharmacology, Boehringer Ingelheim Italia, Milano, Italy.
Duranti
P
P
Giudici
L
L
Schiavone
A
A
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000378:metabolism / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D004285:Dogs; D005260:Female; D005663:Furans; D008297:Male; D009116:Muscarine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009281:Naphthalenes; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines; D010890:Pirenzepine / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D005663:Furans; D009281:Naphthalenes; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010880:Piperidines; D011976:Receptors, Muscarinic; C008446:5-methylfurtrethonium; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D009116:Muscarine; C048172:himbacine; D000109:Acetylcholine