Antimuscarinic potency and functional selectivity of oxotremorine analogs at muscarinic receptor subtypes in the rat.
The potency of six antimuscarinic oxotremorine analogs at sympathetic ganglionic M1 and brainstem M2 muscarinic receptors was compared in the rat. Inhibition of the pressor effects of McNA343 or physostigmine was used as functional indicators of M1 and M2 blockade, respectively. 50% inhibitory doses (ID50) were calculated against both cholinomimetics. Of the analogs, PCA-10 was the most potent, with ID50 values of 0.16 and 0.11 mumol/kg versus McNA343 and physostigmine, respectively. A correlation analysis indicated that these analogs did not functionally discriminate between responses mediated by neuronal M1 or M2 muscarinic receptors in vivo. In contrast, these analogs antagonized M1 ganglionic responses at doses which produced negligible antagonism at cardiac and vascular M2 receptors.
Vargas
H M
HM
Department of Pharmacology, UCLA-School of Medicine 90024-1735.
Ringdahl
B
B
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009116:Muscarine / Q000037:antagonists & inhibitors*; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D010277:Parasympathomimetics; D011760:Pyrrolidinones; D011976:Receptors, Muscarinic; C066831:PCA 10; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D001285:Atropine; D009116:Muscarine; D010830:Physostigmine