Imidazoline Receptors in Cardiovascular and Metabolic Diseases

The site of the hypotensive action of imidazoline compounds, such as clonidine, was first identified within the rostroventrolateral part of the brainstem. Afterwards, it was shown that imidazolines reduced blood pressure when applied in this area, whereas no catecholamine was capable of such an effect. These data led us to suggest the existence of receptors specific for imidazolines 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. As expected, these specific binding sites do not bind the catecholamines. The IBS are classified in two groups: the I1 type, sensitive to clonidine and idazoxan; and the I2 type, sensitive to idazoxan and largely insensitive to clonidine. Imidazoline receptors were shown to be involved in several physiological regulations and pathological processes such as hypertension, diabetes mellitus and some mood disorders. Evidence for their implication in the nervous regulation of blood pressure and in the insulin secretion control will be presented. The hypotensive effects of clonidine-like drugs involve imidazoline receptors (I1Rs), while their most frequent side-effects only involve alpha2-adrenergic receptors. A new class of centrally acting antihypertensive drugs selective for I1Rs is now available. At hypotensive doses, these drugs are devoid of significant side effects. It was shown that the good acceptability of these drugs is likely due to their selectivity for I1Rs.