title: Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers.
abstract: Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (-)-cis-EC, (+)-trans-EC, and (-)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (-)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (-)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (-)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. paulasalgado87@gmail.com.
authors.forename: Paula Regina Rodrigues
authors.initials: PR
authors.lastname: Salgado
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. divilar@hotmail.com.
authors.forename: Diogo Vilar
authors.initials: DV
authors.lastname: da Fonsêca
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. renan_braga123@hotmail.com.
authors.forename: Renan Marinho
authors.initials: RM
authors.lastname: Braga
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil.
authors.forename: Cynthia Germoglio Farias
authors.initials: CG
authors.lastname: de Melo
authors.affiliation: Departamento de Farmácia, Universidade Federal de Sergipe, São Cristóvão-SE, CEP 49100-000, Brazil. lulisynalone@yahoo.com.br.
authors.forename: Luciana Nalone
authors.initials: LN
authors.lastname: Andrade
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. reinaldoan@uol.com.br.|Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. reinaldoan@uol.com.br.
authors.forename: Reinaldo Nóbrega
authors.initials: RN
authors.lastname: de Almeida
authors.affiliation: Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. sousadam@yahoo.com.|Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil. sousadam@yahoo.com.
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry*; D000081005:Cyclohexane Monoterpenes; D004597:Electroshock / Q000009:adverse effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry*; D010433:Pentylenetetrazole / Q000009:adverse effects; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D013237:Stereoisomerism; D013331:Strychnine / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; C006923:carvone; D013331:Strychnine; D010433:Pentylenetetrazole
keywords: anticonvulsant; carvone; enantiomers; essential oils; natural products; para-menthanes; pentylenetetrazole; seizures; stereoisomers; terpene