Maryanoff B E, Nortey S O, Gardocki J F, Shank R P, Dodgson S P
J Med Chem. 1987 May;30(5):880-7. doi: 10.1021/jm00388a023.
Novel sugar sulfamate 1 (McN-4853, topiramate) has been found to exhibit potent anticonvulsant activity analogous to that of phenytoin. In the maximal electroshock seizure test, orally at 2 h in mice, 1 had an ED50 of 39 mg/kg. Orally, 1 had a duration of action in excess of 8 h. Other aspects of the pharmacology of 1, as well as neurochemistry and carbonic anhydrase inhibition, are discussed. The conformational behavior of 1 in solution and in the solid state is discussed. A series of analogues of 1 were synthesized and examined for anticonvulsant properties.
新型氨基磺酸糖1(McN - 4853,托吡酯)已被发现具有与苯妥英类似的强效抗惊厥活性。在最大电休克惊厥试验中,小鼠口服给药2小时后,1的半数有效剂量(ED50)为39毫克/千克。口服时,1的作用持续时间超过8小时。文中还讨论了1的药理学其他方面,以及神经化学和碳酸酐酶抑制作用。探讨了1在溶液和固态中的构象行为。合成了一系列1的类似物并检测其抗惊厥特性。