title: Pharmacological properties of the central antihypertensive agent, moxonidine.
abstract: The sympathetic nervous system plays a central role in the pathophysiology not only of hypertension and other cardiovascular diseases but also metabolic disorders including disturbances of glucose and lipid homeostasis. A centrally acting sympathetic agent is therefore attractive not only for lowering blood pressure, but also intervening with multiple disease processes. Older agents such as clonidine and guanabenz have numerous side effects, including sedation and dry mouth that limit their acceptability to patients. Moxonidine and the related agent rilmenidine have greatly reduced side effects, because they have reduced activity at the α(2) -adrenergic receptors that mediate these undesirable actions. Instead, moxonidine and rilmenidine act primarily through a novel cellular site, termed the I(1) -imidazoline receptor. The molecular biology of the I(1) -imidazoline receptor protein has recently been described, and the cell signaling pathways linked to this protein have been characterized. Moxonidine has unique effects on a number of cell types through this unusual cellular site of action. There are multiple therapeutic implications of these cellular actions, especially for metabolic syndrome and its associated derangements in glucose and lipid metabolism. Finally, the clinical trials that seemed to identify an unfavorable outcome in severe heart failure are dissected and critiqued. We conclude that moxonidine and future successors to this agent could be of great value in treating multiple chronic diseases.
authors: Center for Dental Research, Departments of Dental Educational Services, Physiology, and Pharmacology, Loma Linda University Schools of Dentistry and Medicine, Loma Linda, CA 92350, USA. lpedwards@llu.edu
authors: Lincoln P
authors: LP
authors: Edwards
authors: Terry A
authors: TA
authors: Brown-Bryan
authors: Lancelot
authors: L
authors: McLean
authors: Paul
authors: P
authors: Ernsberger
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000188:drug therapy; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013565:Sympatholytics / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D013565:Sympatholytics; C043482:moxonidine