Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?

Centrally acting imidazoline I(1)-receptor agonists such as moxonidine and rilmenidine induce peripheral sympathoinhibition via the stimulation of hypothetical I(1)-receptors in the rostral ventrolateral medulla. Because of a rather weak affinity for alpha(2)-adrenoceptors, the use of these agents is associated with a lower incidence of adverse reactions, such as sedation and dry mouth, compared with classic centrally acting alpha(2)-adrenoceptor agonists (clonidine, guanfacine, methyldopa). The antihypertensive efficacy of moxonidine and rilmenidine is well documented, and they display a favorable hemodynamic profile. Their tolerability is better than that of the aforementioned centrally acting antihypertensive agents. However, long-term outcome data for moxonidine and rilmenidine are not available, and neither is a quantitative evaluation of their adverse effects. There exists some uncertainty with respect to the identity of the imidazoline I(1)-receptor, which has so far not been cloned. Furthermore, it would be desirable to develop highly selective I(1)-receptor agonists as successor drugs to moxonidine and rilmenidine. Although available data indicate that I(1)-receptor agonists are effective in patients with hypertension, comparative data versus agents such as beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors are required to establish their position in the treatment of hypertension. Finally, I(1)-receptor agonists have potential in the treatment of patients with CHF and those with the metabolic syndrome; syndrome X.