Synephrine hydrochloride (Oxedrine hydrochloride) is an agonist that acts on sympathomimetic α-adrenergic receptor (AR).

Synephrine（0.1-30 μM）在剂量依赖的方式下，对分离的大鼠主动脉显示出强烈的血管收缩效应，该效应可被prazosin、BRL15572和ketanserin显著抑制，而SB216641和propranolol的预处理则不能抑制，表明Synephrine通过肾上腺素能α(1)-受体、5-HT(1D)受体和5-HT(2A)受体施加收缩效应。[2] 尽管Synephrine、1R,2S-去甲肾上腺素和β-苯乙胺对所有三个亚型的Ki值相同，但只有Synephrine是在HEK 293细胞中稳定表达的α1A-AR亚型的部分激动剂，其EC50为4 μM，在100 μM时给出的最大反应等于L-苯肾上腺素最大反应的55.3%。在CHO细胞中稳定表达的α2A-和α2C-AR亚型的功能研究表明，尽管Synephrine的拮抗剂活性低于其部分激动剂效力，但Synephrine可能作为神经末梢存在的α(2A)-和α(2C)-AR亚型的拮抗剂而非激动剂。[3] Synephrine（~100 μM）处理以剂量依赖的方式将L6骨骼肌细胞的基础葡萄糖消耗量提高了50%，而不影响细胞的存活性。Synephrine显著刺激基础或胰岛素刺激的乳酸产生以及葡萄糖消耗。Synephrine处理刺激AMPK的磷酸化，但不刺激Akt，并且Synephrine诱导的葡萄糖消耗和Glut4从细胞质到质膜的转移对AMPK的抑制敏感，而不对PI3激酶的抑制敏感。[4]

给予Synephrine（1 mg/kg，每12小时一次）连续8天，显著改善了因部分门静脉结扎（PVL）或胆管结扎（BDL）引起的门脉高压大鼠的高动力状态，并且在PVL和BDL大鼠中显著降低了门静脉压力、门静脉分支血流量和心脏指数。[1]

In vitro kinase assays [1] : To screen for small molecule inhibitors of ATM kinase activity, an in vitro kinase assay is adapted, and an ELISA assay develops which measured the phosphorylation status of the ATM downstream target p53. Recombinant GST-p53(1-101) and full-length Flag-tagged ATM & ATR are purified for use in the ELISA and in vitro kinase assays. Briefly, Nunc 96 well Maxisorp plates are coated overnight (4 °C) with 2μg of purified, recombinant GST-p53(1-101) in PBS. All subsequent incubations are performed at room temperature. The plates are washed (0.05%v/v-Tween/PBS) before addition of purified recombinant full-length ATM kinase (30 ng–60 ng) in a final volume of 80μL of reaction buffer (20 mM HEPES, 50 mM NaCl, 10 mM MgCl2, 10 mM MnCl2, 1 mM DTT and 1 μM ATP) in the presence or absence of CP-466722. CP-466722 (10 μM) is added to plates in duplicate and the kinase assay is incubated (90 minutes). Plates are washed (0.05%v/v-Tween/PBS), blocked (1hour, 1%w/v-BSA/PBS) and rinsed before anti-Phospho(Ser15)-p53 antibody (1:1000/PBS) is added to the plates and incubated (1hour). To reduce non-specific binding plates are washed (0.05%v/v-Tween/PBS) prior to incubation (1hour) with HRP-conjugated goat anti-rabbit IgG secondary antibody (1:5000/PBS). Secondary antibody that is linked to the phosphorylated GST-p53(1–101) protein is detected with TMB substrate reagent. Plates are developed (15 minutes–30 minutes) and the reaction is stopped (1 M H2SO4 final concentration) before absorbance is determined (λ450 nM). CP-466722 that inhibits ATM kinase activity in ELISA assays, are characterized with respect to inhibition of ATM/ATR kinases using in vitro kinase assays. Western blotting using the anti-Phospho(Ser15)-p53 antibody is used as a readout of ATM/ATR inhibition. Extended analysis of CP466722 (10 μM) against a commercially available panel of kinases is performed by Upstate.