Marques Thiago Henrique Costa, Marques Maria Leonildes Boavista Gomes Castelo Branco, Medeiros Jand-Venes Rolim, Lima Tamires Cardoso, de Sousa Damião Pergentino, de Freitas Rivelilson Mendes
Laboratory of Experimental Neurochemistry Research, Federal University of Piauí (UFPI), Campus Ministro Petrônio Portella, Ininga District, Teresina, Piauí, Brazil.
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.
Pharmacol Biochem Behav. 2014 Sep;124:421-4. doi: 10.1016/j.pbb.2014.06.016. Epub 2014 Jun 23.
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 Research & 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.
癫痫在全球影响着约4000万人。许多药物可阻断癫痫发作，但在预防或治愈这种疾病方面效果甚微。因此，在人体试验之前利用动物模型寻找治疗癫痫的新药很重要。制药行业越来越多地投资于研发领域，以寻求安全有效的新治疗方案，替代现有的癫痫治疗方法。从这个角度来看，天然化合物已在癫痫模型中得到研究，特别是从药用植物中获得的单萜类化合物。在我们的研究中，我们调查了由天然单萜香芹酮制备的合成物质氰基香芹酮（CC），在重复口服给药（CC 25、50和75mg/kg）14天后，对毛果芸香碱（PILO）、戊四氮（PTZ）和印防己毒素（PTX）诱导的小鼠癫痫发作的影响。与溶剂对照组相比，所有测试剂量的CC在PILO、PTZ和PTX组中均显示首次癫痫发作潜伏期延长、癫痫发作动物百分比降低以及死亡动物百分比降低（p<0.05）。然而，用于研究CC作用机制的苯二氮䓬（BZD）拮抗剂氟马西尼并未逆转这些作用。我们的结果表明，在所测试剂量下急性给予CC可在PILO、PTZ和PTX癫痫模型中发挥抗惊厥作用。此外，我们的数据表明，CC可能作用于GABAA的变构位点，这与BDZ作用的位点不同，因为氟马西尼无法逆转CC对所研究癫痫模型相关癫痫发作参数调节的任何作用。应开展新的研究以调查CC在其他神经递质系统中的作用。尽管如此，我们的研究强化了这样一种假设，即CC经过进一步研究后可作为一种新的药物制剂，成为癫痫治疗的一种有前景的替代方案，因为它显示出了抗惊厥作用。
