title: Semicarbazone--a versatile therapeutic pharmacophore for fragment based anticonvulsant drug design.
abstract: During the last fifteen years, semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) was discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroshock (MES) ED₅₀ of i.p. 12.9 mg kg⁻¹. In MES (oral screen), this compound has a protective index (PI = TD₅₀/ED₅₀ > 315) higher than carbamazepine (PI 101), phenytoin (PI > 21.6) and valproate (PI 2.17). The compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole, subcutaneous strychnine, subcutaneous picrotoxin and subcutaneous bicculine. Semicarbazones are also GABA-transaminase inhibitors. Extensive structure- -activity relationship has demonstrated that F, Cl, Br and NO₂ substituents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.
authors.affiliation: Department of Pharmacy, Saroj Institute of Technology and Management Ahimamau, Lucknow-226002 (U.P.), India. snpande65@yahoo.co.in
authors.forename: Surendra Nath
authors.initials: SN
authors.lastname: Pandeya
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D012664:Semicarbazones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D012664:Semicarbazones; D026941:Sodium Channel Blockers; D000612:4-Aminobutyrate Transaminase