E. Savontaus et al., Effects of chronic celiprolol treatment on brown fat, feeding, and drinking in fa/fa Zucker rats, PHARM BIO B, 65(4), 2000, pp. 719-724
Celiprolol is a novel beta-adrenoceptor blocking drug that displays clinica
lly favorable effects on glucose and lipid metabolism. Because some other a
typical beta-adrenoceptor blocking drugs have been described to act as agon
ists on beta(3)-adrenoceptors, we aimed to investigate the effects of celip
rolol on brown fat and beta(3)-adrenoceptors. Chronic treatment of obese fa
/fa Zucker rats with celiprolol (50 mg/kg/day orally for 20 days) increased
GDP binding to brown fat mitochondria by 1.5-fold, whereas beta(3)-adrenoc
eptor agonist ZD7114 ((S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-
(2-methoxyethyl)phenoxyacetamide, 3 mg/kg/day) increased the binding by 3.3
-fold. Weight gain was reduced by 19% due to decreased water and food intak
es in celiprolol-treated rats. Celiprolol did not activate lipolysis in rat
adipocytes in vitro or stimulate human beta(3)-adrenoceptors expressed in
Chinese hamster ovary cells as measured with Cytosensor microphysiometer. T
herefore. celiprolol does not seem to activate brown fat via beta(3)-adreno
ceptors. (C) 2000 Elsevier Science Inc.