TY - JOUR T1 - Inhibition of Serotonin-Induced Vascular Smooth Muscle Cell Proliferation by Sarpogrelate JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1475 LP - 1481 VL - 290 IS - 3 AU - Sushil K. Sharma AU - Peter Zahradka AU - Donald Chapman AU - Hideo Kumamoto AU - Nobuakira Takeda AU - Naranjan S. Dhalla Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/1475.abstract N2 - Antiproliferative behavior of sarpogrelate (Anplag, MCI-9042, (±)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride), a serotonin 2A (5-HT2A) receptor antagonist, was established using radioactive incorporation of [3H]thymidine, [3H]uridine, and [3H]phenylalanine in cultured rat aortic smooth muscle cells in response to a 5-HT-induced cytokine trigger. Fluorescence-activated cell sorting was used to confirm these observations. 5-HT-induced DNA, RNA, and protein synthesis were inhibited maximally at a concentration of 1 μM sarpogrelate. Although other cytokines such as platelet-derived growth factor and endothelin also induced DNA, RNA, and protein synthesis in rat aortic smooth muscle cells, cell proliferation was not influenced by sarpogrelate, even at large pharmacological concentrations (10 μM). Sarpogrelate’s antiproliferative actions were found to be more potent than ketanserin. These data indicate that sarpogrelate operates as a specific inhibitor of 5-HT-mediated cell proliferation and is a good candidate for preventing serotonin-induced neointimal hyperplasia. The American Society for Pharmacology and Experimental Therapeutics ER -