RS-127445 is a selective; high affinity; orally bioavailable serotonin 5-HT2B receptor antagonist. RS-127445 was found to have a 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 receptors 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). RS-127445 (MT-500) was being developed for the prophylactic treatment of migraine. POZEN acquired MT-500 from Roche in November 1999 and assumed full responsibility for its development for migraine prophylaxis.