title: Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?
abstract: 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.
authors.affiliation: Department of Pharmacotherapy, Cardiology and Cardiothoracic Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D054755:Imidazoline Receptors; D010080:Oxazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011955:Receptors, Drug / Q000819:agonists*; D000077769:Rilmenidine
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; C043482:moxonidine; D000077769:Rilmenidine