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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Feb;93(2):437–445. doi: 10.1111/j.1476-5381.1988.tb11451.x

Relative affinities of drugs acting at cholinoceptors in displacing agonist and antagonist radioligands: the NMS/Oxo-M ratio as an index of efficacy at cortical muscarinic receptors.

S B Freedman 1, E A Harley 1, L L Iversen 1
PMCID: PMC1853815  PMID: 3359114

Abstract

1. Radioligand binding assays using [3H]-N-methylscopolamine (NMS) and [3H]-oxotremorine M (Oxo-M) have been devised to predict the efficacy of test compounds at muscarinic receptors in rat cerebral cortex. 2. Muscarinic antagonists, including non-selective and both M1- and M2-selective compounds, displayed similar affinity for both binding assays. 3. Full agonists such as carbachol and muscarine possessed a ratio of potencies against the antagonist versus the agonist ligand (NMS/Oxo-M ratio) of greater than 4000. 4. Compounds which have been shown previously to display partial agonist activity in functional assays e.g. pilocarpine and RS86 had intermediate NMS/Oxo-M ratios of 100-150. A second group of compounds which included oxotremorine had somewhat higher ratios (500-1400). 5. The ratio of affinity constants for the two assays predicted the ability of agonists to stimulate cortical phosphatidyl-inositol turnover. 6. These results suggest that the NMS/Oxo-M ratio may be a useful prediction of efficacy for novel compounds acting at cortical muscarinic receptors.

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Selected References

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