title: Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.
abstract: Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (p<0.05) in PILO, PTZ and PTX groups when compared with vehicle. However, these effects were not reversed by flumazenil, benzodiazepine (BZD) antagonist used to investigate the CC action mechanism. Our results suggest that acute treatment with CC at the doses tested can exert anticonvulsant effects in PILO, PTZ and PTX epilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects.
authors: Laboratory of Experimental Neurochemistry Research, Federal University of Piauí (UFPI), Campus Ministro Petrônio Portella, Ininga District, Teresina, Piauí, Brazil.
authors: Thiago Henrique Costa
authors: TH
authors: Marques
authors: Laboratory of Experimental Neurochemistry Research, Federal University of Piauí (UFPI), Campus Ministro Petrônio Portella, Ininga District, Teresina, Piauí, Brazil.
authors: Maria Leonildes Boavista Gomes Castelo Branco
authors: ML
authors: Marques
authors: Laboratory of Experimental Physiopharmacology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí (UFPI), Campus Ministro Reis Velloso, São Sebatião Avenue, no. 2819, 64202-020 Parnaíba, Piauí, Brazil.
authors: Jand-Venes Rolim
authors: JV
authors: Medeiros
authors: Post-Graduate Program in Pharmaceutics Sciences, Federal University of Sergipe, CEP 49100-000 São Cristovão, Aracajú, Brazil.
authors: Tamires Cardoso
authors: TC
authors: Lima
authors: Center for Health Sciences, Federal University of Paraiba, Campus Universitário I, Castelo Branco District, CEP 58051-900 João Pessoa, Paraiba, Brazil.
authors: Damião Pergentino
authors: DP
authors: de Sousa
authors: Laboratory of Experimental Neurochemistry Research, Federal University of Piauí (UFPI), Campus Ministro Petrônio Portella, Ininga District, Teresina, Piauí, Brazil. Electronic address: rivelilson@pq.cnpq.br.
authors: Rivelilson Mendes
authors: RM
authors: de Freitas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D000081005:Cyclohexane Monoterpenes; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: C000597739:5-isopropenyl-2-methyl-3-oxocyclohexanocarbonitrile; D000927:Anticonvulsants; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D009570:Nitriles
keywords: Anticonvulsant; Cyane-carvone; Mice; Seizures; Terpene