Adrenergic and Nonadrenergic Effects of Imidazoline and Related Antihypertensive Drugs in the Brain and Periphery

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Abstract
In radioligand binding studies the α2-adrenoceptor antagonist ligand [3H]yohimbine binds exclusively to adrenergic sites. However, in addition to binding to α2-adrenoceptor sites, two other ligands, [3H]clonidine and [3H]idazoxan, also bind at nonadrenergic imidazoline sites. Many of the compounds with a high affinity for these imidazoline sites are centrally acting antihypertensive drugs and there is some evidence that these sites are involved in blood pressure regulation. With chronic treatment of rabbits with guanabenz, clonidine, and rilmenidine, down regulation of α2 but not imidazoline sites occurred in forebrain and hind-brain with guanabenz treatment, and in hindbrain with clonidine treatment. However, no change in either imidazoline or α2-adrenoceptor binding site number occurred in animals given chronic rilmenidine treatment. This rank order of effect, guanabenz > clonidine > rilmenidine, is consistent with the α2-adrenoceptor activation by the three drugs in the periphery. In contrast, chronic treatment with guanabenz, clonidine, and rilmenidine had similar effects on blood pressure, heart rate, and responses to intracisternal clonidine. We suggest that stimulation of û½-adrenoceptors cannot account for all the changes in cardiovascular responses observed on chronic treatment and that activation of nonadrenergic imidazoline-preferring sites may contribute to the antihypertensive properties of imidazoline and related compounds. Am J Hypertens 1992;5:58S-63S.

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