Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds.
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.
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004597:Electroshock; D005632:Fructose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D010672:Phenytoin / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D013329:Structure-Activity Relationship; D000077236:Topiramate
D002257:Carbonic Anhydrase Inhibitors; D000077236:Topiramate; D005632:Fructose; D010672:Phenytoin