Muscarinic activity of McN‐A‐343 and its value in muscarinic receptor classification

• Published in: British journal of pharmacology Vol. 90; no. 4; pp. 693 - 700
• Main Authors: Eglen, R.M., Kenny, B.A., Michel, A.D., Whiting, R.L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.1987; Nature Publishing
• Subjects: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - pharmacology; Animals; Biological and medical sciences; Carbachol - pharmacology; Cerebral Cortex - analysis; Cholinergic system; Guinea Pigs; In Vitro Techniques; Male; Medical sciences; Myocardium - analysis; N-Methylscopolamine; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Parasympatholytics - pharmacology; Pharmacology. Drug treatments; Quaternary Ammonium Compounds - pharmacology; Radioligand Assay; Rats; Rats, Inbred Strains; Receptors, Muscarinic - analysis; Receptors, Muscarinic - drug effects; Scopolamine Derivatives - metabolism; Atrium; Agonist; Cerebral cortex; Rat; Cecum; Rodentia; Selectivity; Ileum; In vitro; Vertebrata; Mammalia; Guinea pig; Urinary bladder; Animal; Myocardium; Affinity; Muscarinic receptor; Trachea
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1987.tb11222.x

1 The affinity and potency of McN‐A‐343 (4‐(m‐chlorophenyl‐carbamoyloxy) −2‐butynyltrimethylammonium chloride) has been assessed at a range of M1 and M2 muscarinic receptors. McN‐A‐343 was shown to act as a full agonist at M2 receptors present in the guinea‐pig isolated taenia caeci (–log EC50 = 5.14). McN‐A‐343 exhibited no agonist action in the guinea‐pig ileum, atria, bladder or trachea. 2 McN‐A‐343 was not selective in terms of affinity since its dissociation constants at M1 and M2 binding sites in the rat cerebral cortex and myocardium respectively, were very similar (cortical pPKi = 5.05; myocardial pKi = 5.22). The selectivity previously reported for the compound may be due to differences in intrinsic efficacy and/or tissue receptor reserve. 3 Based on differential antagonist affinities, the muscarinic receptor profile of the taenia caeci, trachea and bladder was similar to that observed in the ileum, but dissimiliar to that observed in the atria.