THE MECHANISM OF DRUG ACTION AT RECEPTOR SURFACES: PART I. INTRODUCTION. A GENERAL INTERPRETATION OF THE ADRENERGIC BLOCKING ACTIVITY OF β-HALOALKYLAMINES

Abstract

An interpretation of the mechanism of action of "Dibenamine" is offered and the conclusion is reached that the excitatory receptors most probably include a carboxylate or phosphate anion as an active center. On the basis of a combination of isosteric and chemical reactivity principles, a precise correlation between structure and pharmacological activity of adrenergic blocking β-haloalkylamines is described. Structural similarities between sympathomimetic amines and adrenergic blockers are uncovered and applied to the interpretation of the activity of several hundred β-haloalkylamines. The crucial point of the discussion revolves about the concept of a phenethylamine pattern illustrated in Figs. 1 and 2 and it is demonstrated that this pattern applies generally to active adrenergic blocking β-haloalkylamines and that it allows predictions of activity.