A β3-AR antagonist
SR 59230A (hydrochloride) is a β3-adrenergic receptor (β3-AR) antagonist (pA2s = 8.76, 7.31, and 6.63 in rat proximal colon, guinea pig atrium, and guinea pig trachea, respectively).1 It is less selective for β3-AR in cells transfected with the human β-AR subtypes (Kis = 16.4, 61.9, and 122 nM for β1-, β2-, and β3-AR, respectively).2 At low concentrations, SR 59230A blocks MDMA-induced hyperthermia, while at high concentrations it blocks hyperthermia but also increases heat loss through an α1-AR antagonistic mechanism.3 In adipocytes, it induces phosphorylation of p38 MAPK via the Gs pathway.4 It has also been used in studies of heart failure to elucidate the role of the β3-ARs.5
1.Manara, L., Badone, D., Baroni, M., et al.Functional identification of rat atypical β-adrenoceptors by the first β3-selective antagonists, aryloxypropanolaminotetralinsBr. J. Pharmacol.117(3)435-442(1996) 2.Hoffman, C., Leitz, M.R., Oberdorf-Maass, S., et al.Comparative pharmacology of human β-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cellsNaunyn-Schmiedeberg's Arch. Pharmacol.369(2)151-159(2004) 3.Bexis, S., and Docherty, J.R.Role of α1- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouseBr. J. Pharmacol.158(1)259-266(2009) 4.Mizuno, K., Kanda, Y., Kuroki, Y., et al.Stimulation of β3-adrenoceptors causes phosphorylation of p38 mitogen-activated protein kinase via a stimulatory G protein-dependent pathway in 3T3-L1 adipocytesBr. J. Pharmacol.135(4)951-960(2002) 5.Gan, R.T., Li, W.M., Xiu, C.H., et al.Chronic blocking of β3-adrenoceptor ameliorates cardiac function in rat model of heart failureChin. Med. J. (Engl.)120(24)2250-2255(2007)
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