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.

3, 4-dihydroxyphenylacetic acid (DOPAC) is a neuronal metabolite of dopamine (DA). DA undergoes monoamine oxidase-catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase, ALDH2. DOPAC exhibits the antiproliferative effect in colon cancer cells. In addition, DOPAC enhances not only the total ALDH activity but also the gene expression of ALDH1A1, ALDH2, and ALDH3A1 in a concentration-dependent manner. The pretreatment of DOPAC completely protects the cells from the acetaldehyde-induced cytotoxicity, thus DOPAC acts as a potential ALDH inducer to prevent the alcohol-induced abnormal reaction.