RS-127445(MT 500) is a selective 5-HT2B receptor antagonist with pKi of 9.5 and pIC50 of 10.4.
IC50 Value: 10.4(pIC50); 9.5(pKi)
Target: 5-HT Receptor
in vitro: RS 127445 is a potent, selective and high affinity serotonin 5-HT2B receptor antagonist with a pIC50 of 10.4. The affinity (pKi) of RS 127445 for the 5-HT2B receptor is 9.5. RS 127445 displays 1000-fold selectivity for 5-HT2B with good bioavailability. RS-127445 is a novel high affinity, selective 5-HT2B receptor antagonist devoid of detectable intrinsic activity. RS-127445 is found to have nM affinity and 1000 fold selectivity for the 5-HT2B receptor. RS-127445 is thus among the highest affinity, most selective 5- HT2B receptor ligands. RS-127445 potently blocks the 5-HT evoked increase in inositol phosphate formation and blocks the 5-HT evoked increases in intracellular calcium concentrations with a potency 1000 times greater than that of yohimbine.
in vivo: RS-127445 is readily absorbed with no obvious dose or route-dependent limitations and rapidly absorbed following both oral and intraperitoneal administration with peak plasma concentrations being achieved within 15 min of dosing. RS-127445 concentration in the plasma are achieved are proportional to the administered dose. RS-127445 administrated at dose of 5 mg/kg with approximately 60% of an intraperitoneal dose and 14% of the oral dose is bioavailable. RS-127445 concentration in the plasma is predicted to fully saturate accessible 5-HT2B receptors can be readily achieved and maintained in the rat. RS-127445 administered at 1 to 10 mg/kg with oral significantly inhibits visceral hypersensitivity up to 35 to 74% provoked by restraint stress. Oral RS-127445 produces a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg/ kg), although RS-127445 has no significant effect on the visceral nociceptive threshold of native rats. RS-127445 administrated orally with 1 to 30 mg/kg also dose -dependently reduce the restraint stress-induced defecation in native and TNBS-treated rats.

5-HT Receptor
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