title: Evaluation of an agonist index: affinity ratio for compounds active on muscarinic cholinergic M2 receptors.
abstract: A protocol for predicting full agonist, partial agonist, and antagonist profiles of compounds with M2 muscarinic cholinergic receptor activity was developed using radioligand binding assay techniques with [3H]-N-methyl scopolamine (NMS) and [3H]-Oxotremorine-M (Oxo-M) as radioligands. Full muscarinic cholinergic receptor agonists such as muscarine and oxotremorine-M expressed a high agonist index (> 3000 for M1 muscarinic cholinergic receptors and > 900 for M2 muscarinic cholinergic receptor), whereas muscarinic receptor antagonists (selective or non-selective) for different receptor subtypes gave a low (0.5-10) agonist index. Functional studies performed on preparations of guinea-pig ileum and heart were consistent with radioligand binding assay experiments. The above results suggest that similarly as already established for the M1 muscarinic cholinergic receptor subtype, evaluation of the [3H]-NMS/[3H]-Oxo-M ratio may provide useful information on the profile of compounds acting at the M2 muscarinic cholinergic receptor subtype. The availability of simple and predictive techniques for the characterization of muscarinic M2 cholinergic receptor agonists, may help the identification of new compounds in therapeutic areas in which stimulation or inhibition of this receptor is desirable.
authors.affiliation: Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Camerino, Italy.
authors.forename: S K
authors.initials: SK
authors.lastname: Tayebati
authors.forename: A
authors.initials: A
authors.lastname: Piergentili
authors.forename: D
authors.initials: D
authors.lastname: Natale
authors.forename: F
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D019832:N-Methylscopolamine / Q000737:chemistry*; D010095:Oxotremorine / Q000737:chemistry*; D011817:Rabbits; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism; D014649:Vas Deferens / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism
chemical_list: D011976:Receptors, Muscarinic; D010095:Oxotremorine; D019832:N-Methylscopolamine