title: Ramatroban (BAY u 3405): a novel dual antagonist of TXA2 receptor and CRTh2, a newly identified prostaglandin D2 receptor.
abstract: It is known that thromboxane A2 (TXA2) contributes to various diseases such as bronchial asthma, ischemic heart disease, cerebrovascular disorders and allergic rhinitis. A number of TXA2 synthase inhibitors and TXA2 receptor (TP receptor) antagonists have been developed to treat these diseases. Ramatroban (BAY u 3405) was developed as a potent TP receptor antagonist with excellent efficacy against allergic rhinitis in many animal models and patients. Recent studies also revealed that ramatroban can block the newly identified PGD2 receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2). PGD2 induces migration and degranulation of eosinophils through CRTh2 and contributes to late-phase inflammation and cell damage. Accordingly, it was considered that ramatroban suppresses the late-phase inflammation via TP receptor and CRTh2 blockade. In terms of the efficacy on vascular systems, it was revealed that ramatroban can suppress the expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in endothelial cells and prevent exacerbation of inflammation by blocking these responses. According to our recent studies in hypercholesterolemic rabbits ramatroban prevents macrophage infiltration through MCP-1 downregulation and neointimal formation after balloon injury and attenuates vascular response to acetylcholine. Therefore, ramatroban may be beneficial in the treatment of atherosclerosis.
authors.affiliation: Department of Medical Engineering, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359, Japan. tir2@hotmail.com.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Takemi
authors.initials: T
authors.lastname: Matsui
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohta
authors.forename: Michitaka
authors.initials: M
authors.lastname: Shichijo
mesh_terms: D000402:Airway Obstruction / Q000188:drug therapy; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002227:Carbazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002986:Clinical Trials as Topic; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006801:Humans; D009297:Nasal Mucosa / Q000098:blood supply; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D013930:Thromboxane-A Synthase / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D002227:Carbazoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; D013930:Thromboxane-A Synthase; C063119:ramatroban; C036293:prostaglandin D2 receptor