RS-127445 hydrochloride (MT 500) is a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist(pKi : 9.5).

5-HT2B:9.5(pKi)

RS 127445 强效地从在 CHO-K1 细胞中表达的人源重组 5-HT2B 受体上位移了 [3H]-5-HT。RS-127445 对 5-HT2B 受体的亲和力（pKi 值）为 9.5±0.1（n=9）。RS-127445 对 5-HT2B 受体具有选择性，其对人源重组 5-HT2A、5-HT2C、5-HT5、5-HT6 和 5-HT7 受体的亲和力大约低 1000 倍，对大鼠脑膜中的 5-HT1A 受体、牛尾核中的 5-HT1B/D 受体、以及兔血小板中的单胺摄取位点也显示出显著低的亲和力[1]。

RS 127445（5 mg kg^-1）通过口服、腹腔注射和静脉注射方式给予大鼠。峰值血浆浓度迅速达到，通过静脉和腹腔注射给药后首次测量时间点（0.08小时）观察到最高浓度，而通过口服给药在0.25小时后达到最高。RS-127445从血浆中清除，其估计的终末消除半衰期约为1.7小时。通过口服和腹腔注射给药时，RS-127445的生物利用度分别约为通过静脉给药的14%和62%。为测试血浆水平是否与给药剂量成比例，RS-127445通过腹腔注射途径以1、3和10 mg kg^-1剂量给予。RS-127445剂量的增加导致其在血浆中浓度成比例增加[1]。

Rats were euthanized.?Right and left external jugular veins were dissected, cleaned of connective tissues and cut into ring segments approximately 5 mm long.?Tungsten hooks (0.125 mm diameter) were inserted through the lumen of the vein and connected to tension transducers.?Tissues were kept in 10 ml organ baths containing Kreb's solution supplemented with cocaine (30 μm), corticosterone (30 μm), ketanserin (0.3 μm) and indomethacin (3 μm) at 37°C at a resting tension of 0.5 g.?Prior to the initiation of any studies, monamine oxidases were inactivated by a 30 min pre exposure of the tissue to pargyline (0.1 mm).?The veins were then exposed to 0.1 μm U46619 (9,11-dideoxy-9 α, 11 aα-methano-epoxy-PGF2α;?a thromboxane A2 mimetic) until a stable contraction was attained.?Acetylcholine (0.1 μm) was used to verify the integrity of the endothelium and to determine the maximum amount of nitric?oxide-dependent relaxation that was achievable.?After washout of the acetylcholine and recontraction with U46619, cumulative concentration-response curves to (±)-α-methyl-5-HT were constructed.?When maximum relaxation was reached, the baths were rinsed, and the tissues were maintained undisturbed for 2 h. Antagonists (RS 127445)were then added to the bath and allowed to equilibrate with the tissue for at least 1 h before a second concentration-response curve to (±)-α-methyl-5-HT was generated[1].