Evaluation of an agonist index: affinity ratio for compounds active on muscarinic cholinergic M-2 receptors

1 A protocol for predicting full agonist, partial agonist, and antagonist p rofiles of compounds with M-2 muscarinic cholinergic receptor activity was: developed using radioligand binding assay techniques with [H-3]-N-methyl sc opolamine (NMS) and [H-3]-Oxotremorine-M (Oxo-M) as radioligands. 2 Full muscarinic cholinergic receptor agonists such as muscarine and oxotr emorine-M expressed a high agonist index (> 3000 for M-1 muscarinic choline rgic receptors and > 900 for M-2 muscarinic cholinergic receptor), whereas muscarinic receptor antagonists (selective or non-selective) for different receptor subtypes gave a low 10.5-10) agonist index. 3 Functional studies performed on preparations of guinea-pig ileum and hear t were consistent with radioligand binding assay experiments, 4 The above results suggest that similarly as already established for the M -1 muscarinic cholinergic receptor subtype, evaluation of the [H-3]-NMS/[H- 3]-Oxo-M ratio may provide useful information on the profile of compounds a cting at the M-2 muscarinic cholinergic receptor subtype, 5 The availability of simple and predictive techniques for the characteriza tion of muscarinic M-2 cholinergic receptor agonists, may help the identifi cation of new compounds in therapeutic areas in which stimulation or inhibi tion of this receptor is desirable.