Mohseni Gholamreza, Ostadhadi Sattar, Akbarian Reyhaneh, Chamanara Mohsen, Norouzi-Javidan Abbas, Dehpour Ahmad-Reza
Department of Anesthesiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Epilepsy Behav. 2016 Dec;65:49-55. doi: 10.1016/j.yebeh.2016.08.001. Epub 2016 Nov 19.
Dextrometrophan (DM), widely used as an antitussive, has recently generated interest as an anticonvulsant drug. Some effects of dextrometrophan are associated with alterations in several pathways, such as inhibition of nitric oxide synthase (NOS) enzyme and N-methyl d-aspartate (NMDA) receptors. In this study, we aimed to investigate the anticonvulsant effect of acute administration of dextrometrophan on pentylenetetrazole (PTZ)-induced seizures and the probable involvement of the nitric oxide (NO) pathway and NMDA receptors in this effect. For this purpose, seizures were induced by intravenous PTZ infusion. All drugs were administrated by intraperitoneal (i.p.) route before PTZ injection. Our results demonstrate that acute DM treatment (10-100mg/kg) increased the seizure threshold. In addition, the nonselective NOS inhibitor L-NAME (10mg/kg) and the neural NOS inhibitor, 7-nitroindazole (40mg/kg), at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of DM (3mg/kg), while the inducible NOS inhibitor, aminoguanidine (100mg/kg), did not affect the anticonvulsant effect of DM. Moreover, the NOS substrate l-arginine (60mg/kg) blunted the anticonvulsant effect of DM (100mg/kg). Also, NMDA antagonists, ketamine (0.5mg/kg) and MK-801 (0.05mg/kg), augmented the anticonvulsant effect of DM (3mg/kg). In conclusion, we demonstrated that the anticonvulsant effect of DM is mediated by a decline in neural nitric oxide activity and inhibition of NMDA receptors.
右美沙芬（DM）作为一种广泛使用的止咳药，最近作为一种抗惊厥药物引起了人们的关注。右美沙芬的一些作用与多种途径的改变有关，例如抑制一氧化氮合酶（NOS）和N-甲基-D-天冬氨酸（NMDA）受体。在本研究中，我们旨在研究急性给予右美沙芬对戊四氮（PTZ）诱导的癫痫发作的抗惊厥作用，以及一氧化氮（NO）途径和NMDA受体在该作用中可能的参与情况。为此，通过静脉注射PTZ诱导癫痫发作。所有药物均在注射PTZ前通过腹腔注射给药。我们的结果表明，急性给予DM（剂量为10 - 100mg/kg）可提高癫痫发作阈值。此外，非选择性NOS抑制剂L-NAME（10mg/kg）和神经型NOS抑制剂7-硝基吲唑（40mg/kg），在对癫痫发作阈值无影响的剂量下，增强了DM（3mg/kg）的抗惊厥作用，而诱导型NOS抑制剂氨基胍（100mg/kg）对DM的抗惊厥作用没有影响。此外，NOS底物L-精氨酸（60mg/kg）减弱了DM（100mg/kg）的抗惊厥作用。同样，NMDA拮抗剂氯胺酮（0.5mg/kg）和MK-801（0.05mg/kg）增强了DM（3mg/kg）的抗惊厥作用。总之，我们证明了DM的抗惊厥作用是由神经型一氧化氮活性的下降和NMDA受体的抑制介导的。
