Oliveira M S, Furian A F, Rambo L M, Ribeiro L R, Royes L F F, Ferreira J, Calixto J B, Mello C F
Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Neuroscience. 2008 Apr 9;152(4):1110-8. doi: 10.1016/j.neuroscience.2008.01.005. Epub 2008 Jan 12.
There is evidence that prostaglandin E2 (PGE2) facilitates the seizures induced by pentylenetetrazol (PTZ), but the role of PGE2 receptors (EPs) in the development of seizures has not been evaluated to date. In the current study we investigated whether selective EP ligands alter PTZ-induced seizures in adult male Wistar rats by electrographic methods. Selective antagonists for EP1 (SC-19220, 10 nmol, i.c.v.), EP3 (L-826266, 1 nmol, i.c.v.) and EP4 (L-161982, 750 pmol, i.c.v.) receptors, and the selective EP2 agonist butaprost (100 pmol, i.c.v.) increased the latency for clonic and generalized tonic-clonic seizures induced by PTZ. These data constitute pharmacological evidence supporting a role for EPs in the seizures induced by PTZ. Although more studies are necessary to fully evaluate the anticonvulsant role these compounds and their use in the clinics, EP ligands may represent new targets for drug development for convulsive disorders.
有证据表明前列腺素E2（PGE2）会促进戊四氮（PTZ）诱发的癫痫发作，但迄今为止，PGE2受体（EPs）在癫痫发作发展过程中的作用尚未得到评估。在本研究中，我们通过脑电图方法研究了选择性EP配体是否会改变成年雄性Wistar大鼠中PTZ诱发的癫痫发作。EP1（SC-19220，10 nmol，脑室内注射）、EP3（L-826266，1 nmol，脑室内注射）和EP4（L-161982，750 pmol，脑室内注射）受体的选择性拮抗剂，以及选择性EP2激动剂布他前列素（100 pmol，脑室内注射），均延长了PTZ诱发的阵挛性发作和全身性强直-阵挛性发作的潜伏期。这些数据构成了药理学证据，支持EPs在PTZ诱发的癫痫发作中发挥作用。尽管需要更多研究来全面评估这些化合物的抗惊厥作用及其在临床上的应用，但EP配体可能代表了惊厥性疾病药物开发的新靶点。
