Muscarinic and antimuscarinic activity of acetamides related to oxotremorine in the guinea pig urinary bladder. 1987

B Ringdahl, and M E Markowicz

Eight acetamide analogs of oxotremorine, shown previously to be full or nearly full muscarinic agonists on the isolated guinea pig ileum, were investigated for muscarinic activity on muscle strips of guinea pig urinary bladder. Several compounds demonstrated pronounced organ selectivity when compared to carbachol by being partial agonists or antagonists on the bladder. For example, oxotremorine and BM 34, both potent, full agonists on the ileum, were partial agonists, the latter producing less than one-half the maximum response of carbachol. BM 5 elicited no significant response, but instead was a potent antagonist to carbachol. Schild analysis with BM 5 and BM 61 indicated no muscarinic receptor heterogeneity between the bladder and ileum. Also dissociation constants of agonists and partial agonists generally agreed with those determined previously on the ileum. Furthermore, the relative efficacy of each agonist appeared to be similar in the two tissues, confirming the homogeneity of muscarinic receptors in the bladder and ileum with respect to the compounds studied. Compounds having high affinity and low intrinsic efficacy, e.g., BM 5, thus may stimulate contractile responses on the ileum and block responses on the bladder and therefore display tissue selectivity without discriminating between tissue receptors. It is suggested that this selectivity is derived from a smaller effective receptor reserve for muscarinic agonists in the bladder.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D010095 Oxotremorine A non-hydrolyzed muscarinic agonist used as a research tool. Oxytremorine
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D001743 Urinary Bladder A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION. Bladder,Bladder Detrusor Muscle,Detrusor Urinae,Bladder Detrusor Muscles,Bladder, Urinary,Detrusor Muscle, Bladder,Detrusor Muscles, Bladder
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000081 Acetamides Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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