IDRA-21

IDRA-21是种AMPA受体的正別構調節劑，也是苯丙噻二嗪的衍生物，也是一种手性分子，(+)-IDRA-21是其活性形式。[1]

IDRA-21
法律規範狀態
法律規範
  • 美：試驗用新藥
识别
  • 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
CAS号22503-72-6  checkY
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
化学
化学式C8H9ClN2O2S
摩尔质量232.68 g·mol−1
3D模型（JSmol）
  • CC1NC2=C(C=C(C=C2)Cl)S(=O)(=O)N1
  • InChI=1S/C8H9ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-5,10-11H,1H3 ☒N
  • Key:VZRNTCHTJRLTMU-UHFFFAOYSA-N ☒N

在动物实验中，IDRA-21表现出了有促进学习的效果，并能明显改善学习和记忆。在逆转阿普唑仑或东莨菪碱诱发的认知障碍方面，有着约比茴拉西坦10到30倍的效力，[2][3]且在单次服用后，可产生长达48小时的持续效应，[4]其作用机制，被认为是通过促进大脑突触间的诱导LTP达到的。[5]

正常情况下，IDRA-21或许不产生神经毒性，[6]但可能会加重中风或癫痫发作后，因全身缺血所造成的神经元损伤。[7]

与安帕金或苯甲酰哌啶衍生的AMPA受体增效剂相比，IDRA-21药效优于CX-516，低于CX-546。[8]与IDRA-21相比，效力更好的苯丙噻二嗪类衍生物已被开发出来，[9][10]但这些衍生物，各所获的研究程度并不一样，苯甲酰基哌啶（benzoylpiperidine）和苯甲酰基吡咯烷CX系列（benzoylpyrrolidine CX-series）药物，在临床开发中更受青睐，这或是由于它们在高剂量使用时，具有更有利的毒性特征。[11]

另见
  • 正別構調節劑

参考文献
  1. Uzunov DP, Zivkovich I, Pirkle WH, Costa E, Guidotti A. . Journal of Pharmaceutical Sciences. August 1995, 84 (8): 937–42. PMID 7500277. doi:10.1002/jps.2600840807.
  2. Thompson DM, Guidotti A, DiBella M, Costa E. . Proceedings of the National Academy of Sciences of the United States of America. August 1995, 92 (17): 7667–71. Bibcode:1995PNAS...92.7667T. PMC 41206 可免费查阅. PMID 7644474. doi:10.1073/pnas.92.17.7667 可免费查阅.
  3. Zivkovic I, Thompson DM, Bertolino M, Uzunov D, DiBella M, Costa E, Guidotti A. . The Journal of Pharmacology and Experimental Therapeutics. January 1995, 272 (1): 300–9. PMID 7815345.
  4. Buccafusco JJ, Weiser T, Winter K, Klinder K, Terry AV. . Neuropharmacology. January 2004, 46 (1): 10–22. PMID 14654093. S2CID 26443642. doi:10.1016/j.neuropharm.2003.07.002.
  5. Arai A, Guidotti A, Costa E, Lynch G. . NeuroReport. September 1996, 7 (13): 2211–5. PMID 8930991. S2CID 35888339. doi:10.1097/00001756-199609020-00031.
  6. Impagnatiello F, Oberto A, Longone P, Costa E, Guidotti A. . Proceedings of the National Academy of Sciences of the United States of America. June 1997, 94 (13): 7053–8. Bibcode:1997PNAS...94.7053I. PMC 21283 可免费查阅. PMID 9192690. doi:10.1073/pnas.94.13.7053 可免费查阅.
  7. Yamada KA, Covey DF, Hsu CY, Hu R, Hu Y, He YY. . Annals of Neurology. May 1998, 43 (5): 664–9. PMID 9585363. S2CID 39977647. doi:10.1002/ana.410430517.
  8. Nagarajan N, Quast C, Boxall AR, Shahid M, Rosenmund C. . Neuropharmacology. November 2001, 41 (6): 650–63. PMID 11640919. S2CID 7796112. doi:10.1016/S0028-3908(01)00133-2.
  9. Phillips D, Sonnenberg J, Arai AC, Vaswani R, Krutzik PO, Kleisli T, et al. . Bioorganic & Medicinal Chemistry. May 2002, 10 (5): 1229–48. CiteSeerX 10.1.1.113.7845 可免费查阅. PMID 11886787. doi:10.1016/S0968-0896(01)00405-9.
  10. Arai AC, Xia YF, Kessler M, Phillips D, Chamberlin R, Granger R, Lynch G. . Molecular Pharmacology. September 2002, 62 (3): 566–77. PMID 12181433. S2CID 16182942. doi:10.1124/mol.62.3.566.
  11. Black MD. . Psychopharmacology. April 2005, 179 (1): 154–63. PMID 15672275. S2CID 5869366. doi:10.1007/s00213-004-2065-6.
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