Aditya S
Department of Pharmacology, Dr. Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Sector 25, Chandigarh, India.
J Postgrad Med. 2012 Oct-Dec;58(4):275-85. doi: 10.4103/0022-3859.105448.
Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.
传统抗凝剂存在诸多已被充分记录的缺点,这促使人们寻求理想的抗凝剂,从而催生了大量新型抗凝分子。这些新型药物直接作用于凝血级联反应的特定环节,包括新型低分子量肝素(阿度肝素)、超低分子量肝素(赛莫肝素、RO-14)、活化因子II抑制剂(达比加群、AZD0837)、因子X抑制剂(利伐沙班、阿哌沙班、依度沙班、贝曲沙班)、因子IX抑制剂(REG1,2)、因子XI抑制剂(反义寡核苷酸、BMS 262084、克拉伐定A)、因子VII/组织因子抑制剂(替法可吉、PCI 274836、BMS 593214)、因子V抑制剂(重组水蛭素、索卢林)、因子VIII抑制剂(TB402)、双靶点凝血酶/因子X抑制剂(EP21709、他诺吉兰)以及新型维生素K拮抗剂(替卡法林)。直接凝血酶抑制剂和因子X抑制剂在临床应用方面最为先进。本文讨论了抗凝剂新靶点研发的最新进展。使用“抗凝剂”、“血液凝固抑制剂”、“抗凝剂与静脉血栓栓塞”、“抗凝剂与心房颤动”以及“抗凝血酶”等检索词,对Medline、EMBASE、Cochrane数据库、Medscape、SCOPUS和clinicaltrials.gov进行了检索。筛选了2007年至2012年发表的讨论药理学和/或临床试验的期刊文章。