This study investigated how targeting both the sympathetic nervous system and the adipose tissue (adiponectin secretion), with a drug selective for non-adrenergic I1-imidazoline receptors (I1Rs), may represent a new concept in metabolic syndrome therapy. LNP599 [3-chloro-2-methyl-phenyl)-(4-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine hydrochloride] selectively bound to I1Rs with nanomolar affinity. The presence of I1Rs was demonstrated by showing that LNP599 had a specific stimulatory action on adiponectin secretion in adipocytes. LNP599 caused decreased sympathetic activity, and long-term treatment of spontaneously hypertensive heart failure rats demonstrated favorable effects on blood pressure, body weight, insulin resistance, glucose tolerance, lipid profile, and increased plasma adiponectin. The results demonstrate that the use of one drug with both actions may constitute an innovative treatment for the metabolic syndrome.
See article at J Pharmacol Exp Ther 2013, 346:370–380.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics