When injected into the medullary site of the hypotensive action of
clonidine,
imidazolines and related compounds decrease blood pressure (BP), whereas no phenylethylamine compounds were capable of producing such an effect at the same site. There is much biochemical and pharmacologic evidence to support the involvement of
imidazoline receptors in the regulation of vasomotor tone as well as in the mechanism of action of some centrally acting
antihypertensive drugs.
Imidazoline-specific binding sites, which do not recognize
catecholamines, have been described in various tissues. Functional studies using selective antagonists have confirmed that the hypotensive effects of
clonidine-like drugs are mediated, at least in part, by nonadrenergic
imidazoline-specific receptors, whereas their
sedative action clearly involves alpha2-adrenergic receptors located in the locus coeruleus. Compared with
clonidine, newer centrally acting
antihypertensive drugs such as
rilmenidine are more selective for
imidazoline receptors than for alpha2-adrenergic receptors. This selectivity may explain the reduced incidence of side effects of these drugs at therapeutic doses. Very recently,
imidazoline-like compounds with no affinity and no activity at alpha2-adrenergic receptors have become available. Some of these compounds lowered the BP when injected centrally, indicating that an action on
imidazoline I1 receptors alone is sufficient to cause
hypotension. Nevertheless,
imidazoline receptors and alpha2-adrenoceptors cooperate in the control of the vasomotor tone and in the hypotensive action of centrally acting hybrid drugs (ie, drugs that bind to both types of receptor). Additional noncardiovascular effects of
imidazoline-like drugs have also been described, such as insulin secretion stimulation and renal
sodium reabsorption inhibition. These effects may account for the long-term benefits of
imidazoline selective drugs, such as
rilmenidine.