title: Newer GABA derivatives for the treatment of epilepsy including febrile seizures: a bioisosteric approach.
abstract: The present study aims at design and synthesis of newer gamma-aminobutyric acid (GABA) derivatives with the combination of thiosemicarbazone and GABA pharmacophores in order to develop newer anticonvulsants. The reported compounds were designed as bioisosteric analogues of GABA semicarbazones. The structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. Initial anticonvulsant screening was performed using intraperitoneal (i.p.) maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and subcutaneous picrotoxin (scPIC)-induced seizure threshold tests. A model involving 22-day old rat pups was also employed to further screen the effects of the test compounds against hyperthermia-induced febrile seizures. Only compounds 1 and 11 were found to be active in the MES test. Most of the compounds were found to be effective in the scPIC and febrile seizure models and very few compounds showed protection in scPTZ and scSTY models. This is the first report on these new GABA derivatives effective in the treatment of febrile seizures.
authors.affiliation: Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Vidya Vihar, Pilani 333031, Rajasthan, India.
authors.forename: Jegadeesan Vaigunda
authors.initials: JV
authors.lastname: Ragavendran
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.forename: Srikanth
authors.initials: S
authors.lastname: Kotapati
authors.forename: James
authors.initials: J
authors.lastname: Stables
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy*; D005334:Fever; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D003294:Seizures, Febrile / Q000139:chemically induced / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid