RS-127445 hydrochloride 是一种有效的，具有口服活性的，高亲和力选择性 5-HT_2B 受体拮抗剂，pK_i 为 9.5，比作用于其他受体和离子通道的选择性高 1000 倍。

RS-127445 hydrochloride is a selective, high affinity, orally bioavailable 5-HT 2B receptor antagonist with a pK i of 9.5. RS-127445 hydrochloride shows 1000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites.

Solid

sPLA2 5.5 (pKi) 5-HT3 Receptor <6 (pK

RS-127445 is found to has nanomolar affinity for the 5-HT2B receptor (pKi=9.5±0.1) and 1,000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites. RS-127445 potently displaces [H]-5-HT from human recombinant 5-HT2B receptors expressed in CHO-K1 cells. The affinity (pKi value) of RS-127445 for the 5-HT2B receptor is 9.5±0.1 (n=9). RS-127445 is selective for the 5-HT2B receptor, having approximately 1000 fold lower affinity for the human recombinant 5-HT2A, 5-HT2C, 5-HT5, 5-HT6 and 5-HT7 receptors, a 5-HT1A receptor in rat brain membranes, a 5-HT1B/D receptor in bovine caudate, and a monoamine uptake site in rabbit platelets. RS-127445 potently blocks the 5-HT (10 nM) evoked increases in

In rats, the fraction of RS-127445 that is bioavailable via the oral or intraperitoneal routes is 14 and 60% respectively. Intraperitoneal administration of RS-127445 (5 mg/kg) produced plasma concentrations predicted to fully saturate accessible 5-HT 2B receptors for at least 4 h.RS-127445 (5 mg/kg) is administered to rats by oral, intraperitoneal and intravenous routes. Peak plasma concentrations are rapidly achieved with the highest concentrations being found at the first time-point measured following intravenous and intraperitonael administration (0.08 h) and by 0.25 h following dosing by the oral route of administration. RS-127445 is cleared from plasma with an estimated terminal elimination half-life of approximately 1.7 h. The bioavailability of RS-127445, when administered by the oral and intraperitoneal routes is approximately 14 and 62% of that obtained by

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Bonhaus DW, et al. RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist. Br J Pharmacol. 1999 Jul;127(5):1075-82.
[2]. Bassil AK, et al. Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology. Br J Pharmacol. 2009 Sep;158(1):252-8

In Vitro: DMSO : ≥ 31 mg/mL (97.55 mM)H₂O : 2.27 mg/mL (7.14 mM; ultrasonic and warming and heat to 60°C)