RS-127445

RS-127445 is a selective; high affinity; orally bioavailable serotonin 5-HT2B receptor antagonist. RS-127445 was found to have 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 antagonized 5-HT-evoked formation of inositol phosphates (pK (B) = 9.5+/-0.1) and 5-HT-evoked increases in intracellular calcium (pIC50 = 10.4+/-0.1) . RS-127445 also blocked 5-HT-evoked contraction of rat isolated stomach fundus (pA2 = 9.5+/-1.1) and (+/-) alpha-methyl-5-HT-mediated relaxation of the rat jugular vein (pA2 = 9.9+/-0.3) .