The effects of chemical structure on the affinity of compounds for acetylcholine receptors

Abstract

The results obtained in the study of these antagonists show that the assumptions of Barlow, Scott and Stephenson (1963), that affinity is made up of components which are additive, is far too simple. An extreme example is the effect of replacing esters (—CO—0—) by ethylene (-CH₂CH₂-); in the monophenyl series this increases affinity whereas in the diphenyl series it decreases affinity. On the other hand, there is no obvious relationship between the effects of substituents on affinity and the affinity itself. It appears, rather, that effects of changes in structure on affinity are related to the chemical nature of the compounds and within series, for example, within the "lower analogues" or within the "higher analogues", the effects do follow a regular pattern, indicating that the binding is made up of components which are additive. The differences between the series, however, indicate that different types of molecule bind in different ways and even within series it appears that there are slight differences in the ways in which the individual compounds become bound

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