Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers

• Main Authors: Paula Regina Rodrigues Salgado, Diogo Vilar da Fonsêca, Renan Marinho Braga, Cynthia Germoglio Farias de Melo, Luciana Nalone Andrade, Reinaldo Nóbrega de Almeida, Damião Pergentino de Sousa
• Format: Article
• Language: English
• Published: MDPI AG 2015-10-01
• Series: Molecules
• Subjects: anticonvulsant; carvone; stereoisomers; terpene; natural products; essential oils; pentylenetetrazole; seizures; para-menthanes; enantiomers
• Online Access: http://www.mdpi.com/1420-3049/20/11/19649

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.