Imidazoline receptors: from basic concepts to recent developments.

Abstract

The existence is now fully demonstrated of binding sites specifically recognizing the imidazoline structure or similar chemical structures, both in the brain and in certain peripheral tissues, including the kidney, some of which participate in the control of blood pressure. These binding sites are different from alpha 2-adrenoceptors, both functionally and biochemically. The fact that at least medullary binding sites are associated with a precise function, i.e., modulation of sympathetic activity of central origin and therefore the regulation of vasomotor tone, indicates that they are true receptors. These imidazoline receptors of the ventrolateral region of the medulla play an important role in the mechanism of the hypotensive action of substances such as clonidine or rilmenidinc. Confirmation of dual pharmacological mechanisms involved in the hypotensive and sedative effects, respectively, of these drugs has justified attribution of the hypotensive effect to involvement of imidazoline receptors in the region of the medulla mentioned and the sedative effect to activation of classic alpha 2-adrenoceptors of the locus ceruleus. This distinction between to mechanisms opens up a novel approach to the development of new centrally acting antihypertensive substances free of the troublesome adverse effects of the first generation. Many questions remain unanswered, including the precise nature of the endogenous ligand(s) of imidazoline receptors, the structure of the receptor and its mechanisms of coupling to second messenger, the possible existence of variants of these receptors, their mode of interaction with alpha-adrenoceptors, and identification of true subtypes of these imidazoline receptors.