Molecular Pharmacology, Vol 7, 357-366, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Ion Size and Activity at Acetylcholine Receptors

¹ Departments of Chemistry and Pharmacology, University, of Edinburgh, Scotland

The apparent molal volumes at infinite dilution, _r^o, of a number of quaternary ammonium salts, tested on the isolated frog rectus and guinea pig ileum preparations, have been determined from precise pycnometric density measurements with dilute aqueous solutions at 25°. In these salts the differences in _r^o for related compounds arise largely from differences in intrinsic volume.

The apparent molal volumes have been compared with the activity and affinity of the compounds at the acetylcholine receptors of the frog rectus and guinea pig ileum. Increases in size are associated with increases in affinity at both types of receptor, but efficacy (ability to activate receptors) is decreased. It is suggested that efficacy is limited by the ability of the ions to penetrate to sites within the receptor at which they can act to produce a change in the conformation of the receptor.