Description
(±)-Synephrine is an alkaloid with vasoconstrictor and metabolic activities. It binds to α
1A-, α
2A-, and α
2C-adrenergic receptors (ARs; K
is = 78, 36.7, and 24.4 μM, respectively). (±)-Synephrine is an agonist of α
1A-ARs in HEK293 cells (EC
50 = 4 μM in a reporter assay) but not in CHO cells expressing α
2A- or α
2C-AR. It also acts as an antagonist of α
1A-, α
2A-, and α
2C-ARs, inhibiting L-phenylephrine-induced activation of α
1A-AR in HEK293 cells and activation of α
2A- and α
2C-ARs induced by the α
2-AR agonist medetomidine in CHO cells (IC
50s = 12.8, 26, and 27.3 μM, respectively, in reporter assays). (±)-Synephrine induces contractions in isolated rabbit aortic rings (EC
50 = 6.2 μg/ml) and increases ligation-induced mean arterial pressure in rats when administered at a dose of 2 mg/kg per day. It induces lipolysis in isolated rat and human adipocytes when used at concentrations of 100 and 1,000 μg/ml. (±)-Synephrine (50 μM) increases phosphorylation of Akt and AMP-activated protein kinase (AMPK) and translocation of Glut4 to the plasma membrane, as well as increases insulin-induced glucose consumption in L6 muscle cells when used at concentrations ranging from 25 to 200 μM.
