Muscarinic activity in the isolated guinea pig ileum of some carboxamides related to oxotremorine.
A series of structural analogues of the potent oxotremorine-like agent N-(4-pyrrolidino-2-butynyl)-N-methyl-acetamide (1) was investigated for muscarinic activity in the isolated guinea pig ileum. Substitution of larger alkyl groups for the acetyl methyl group of 1 results in an attenuation of muscarinic potency. The observation that the agonist N-(4-dimethylamino-2-butynyl)-N-methylpropionamide (6) has a dissociation constant (KA = 5.1 X 10(-5) M), estimated after elimination of spare receptors with dibenamine, similar to that of the antagonist N-(4-dimethylamino-2-butynyl)-N-methyl-2,2-dimethylpropionamide (11) suggests that the decrease in muscarinic agonist activity with increasing substitution is due mainly to a loss of efficacy. The N-methyl group of 1 is essential for muscarinic activity since its replacement by a hydrogen atom or an ethyl group yields antagonists.
D000818:Animals; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D003983:Dibenzylchlorethamine; D010095:Oxotremorine