Involvement of imidazoline receptors (IR) in the regulation of vasomotor tone as well as in the mechanism of action of some centrally acting antihypertensives has received tremendous attention. To date, pharmacological studies have allowed the characterization of three main imidazoline receptor classes, the I(1) -imidazoline receptor which is involved in central inhibition of sympathetic tone to lower blood pressure, the I(2) -imidazoline receptor which is an allosteric binding site of monoamine oxidase B (MAO-B), and the I(3) -imidazoline receptor which regulates insulin secretion from pancreatic β-cells. All three imidazoline receptors represent important targets for cardiovascular research. The hypotensive effect of clonidine-like centrally acting antihypertensives was attributed both to α(2) -adrenergic receptors and nonadrenergic I(1) -imidazoline receptors, whereas their sedative action involves activation of only α(2) -adrenergic receptors located in the locus coeruleus. Since more selective I(1) -imidazoline receptors ligands reduced incidence of typical side effects of other centrally acting antihypertensives, there is significant interest in developing new agents with higher selectivity and affinity for I(1) -imidazoline receptors. The selective imidazoline receptors agents are also more effective in regulation of body fat, neuroprotection, inflammation, cell proliferation, epilepsy, depression, stress, cell adhesion, and pain. New agonists and antagonists with high selectivity for imidazoline receptor subtypes have been recently developed. In the present review we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the theoretical studies of imidazoline receptor ligands.
© 2011 Blackwell Publishing Ltd.