Imidazoline receptors in cardiovascular and metabolic diseases

The site of the hypotensive action of imidazoline compounds, such as clonid ine, was first identified within the rostroventrolateral part of the brains tem. Afterwards, it was shown that imidazolines reduced blood pressure when applied in this area, whereas no catecholamine was capable of such an effe ct. These data led us to suggest the existence of receptors specific for im idazolines different from the alpha -adrenergic receptors. Soon after, the existence of imidazoline binding sites (IBS) was reported in the brain and in a variety of peripheral tissues including pancreatic gland and kidney. A s expected, these specific binding sites do not bind the catecholamines. Th e IBS are classified in two groups: the I-1 type, sensitive to clonidine an d idazoxan; and the I-2 type, sensitive to idazoxan and largely insensitive to clonidine. Imidazoline receptors were shown to be involved in several p hysiological regulations and pathological processes such as hypertension, d iabetes mellitus and some mood disorders. Evidence for their implication in the nervous regulation of blood pressure and in the insulin secretion cont rol will be presented. The hypotensive effects of clonidine-like drugs invo lve imidazoline receptors (I(1)Rs), while their most frequent side-effects only involve alpha (2)-adrenergic receptors. A new class of centrally actin g antihypertensive drugs selective for I(1)Rs is now available. At hypotens ive doses, these drugs are devoid of significant side effects. It was shown that the good acceptability of these drugs is likely due to their selectiv ity for I(1)Rs.