BMY 7378 dihydrochloride 是选择性 α1D 肾上腺素受体拮抗剂，也是5-HT1A受体部分激动剂。它同表达克隆大鼠?α1D-AR?的膜结合的亲和力?(Ki=2?nM)??是同克隆大鼠?α1A-AR?(Ki=800?nM)?或仓鼠?α1B-AR?(Ki=600?nM)?结合的亲和力?的100?以上。

BMY-7378, α1D-adrenergic receptor antagonist, is a weak partial agonist/antagonist of 5-HT1A receptor.

在大鼠体内,BMY7378（0.25-5 mg/kg,s.c.）剂量依赖性降低8-OH-DPAT（0.75 mg/kg,s.c.）诱导的前爪踩踏和头部摇晃.在麻醉大鼠的腹侧海马体中,大鼠体内微量渗析检测显示,BMY7378使5-HT释放出现剂量依赖性的显著减少.BMY7378 (pA2为8.67)与去甲肾上腺素作用可使大鼠主动脉收缩,效果比育亨宾 (pA2为6.62)高约100倍.BMY7378 (pA2：6.48)会拮抗人体隐静脉(α2C-肾上腺素受体)中去甲肾上腺素引起的收缩响应,效果比育亨宾(pA2为7.56)低10倍.

BMY7378对α1D-肾上腺素受体亚型的作用有选择性{PKi: α1b-肾上腺素受体6.2（仓鼠）,7.2（人）；α1c-肾上腺素受体 6.1（牛）,6.6（人）；α1d-肾上腺素受体8.2（大鼠）,9.4（人）}。BMY7378对α2c-肾上腺素受体的选择性（pKi：6.54）是其他α2-肾上腺素受体的10倍。在大鼠中缝背核中,BMY7378（1-30 nM）具有剂量依赖性的抑制作用。

Phosphatase activities are determined on immunoprecipitates of the phosphatases. Briefly, 2×106 K562 cells are treated for 18 hr with Salubrinal (20 μM), PSI (10 nM), the combination of both drugs or okadaic acid (100 nM). After washing with PBS, cells are lysed for 15 min on ice either in PP1LB (for determination of PP1γ-activity; 20 mM Tris-HCl, pH 7.5, 1% Triton X-100, 10% glycerol, 132 mM NaCl, Roche complete protease inhibitor ) or in RIPA (for PP2A), supplemented with Roche complete protease inhibitor). Cell lysates containing 500 μg (PP1γ) or 300 μg (PP2A) protein are immunoprecipitated overnight at 4°C with 2-3 μg of the appropriate antibodies and then incubated with Protein A-Sepharose. Immunoprecipitates are washed three times in lysis buffer, followed by resuspension in phosphatase assay buffer (PP2A: 20 mM Tris-HCl, pH7.5, 0.1 mM CaCl2; PP1γ: 50 mM Tris HCl pH 7.0, 0.2 mM MnCl2, 0.1 mM CaCl2, 125 μg/mL BSA, 0.05% Tween 20), supplemented with 100 μM 6,8-difluoro-4-methyl-umbelliferyl phosphate (DiFMUP). Precipitates are allowed to react with substrate for 1 hr at 37°C on an Eppendorf Thermoshaker, centrifuged and DiFMU fluorescence is measured on a BioTek Lambda Fluoro 320 microplate reader (360 nmex/460 nmem). Phosphatase activities are given as percent change relative to the control (DMSO treated cells)[1].

21102-95-4

C22H33Cl2N3O3

458.42

BMY7378 HCl;BMY 7378 dihydrochloride

H2O:84 mg/mL (183.2 mM)
DMSO:85 mg/mL (185.4 mM)
Ethanol:16 mg/mL (34.9 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years