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  • Title: Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors.
    Author: Mohseni G, Ostadhadi S, Akbarian R, Chamanara M, Norouzi-Javidan A, Dehpour AR.
    Journal: Epilepsy Behav; 2016 Dec; 65():49-55. PubMed ID: 27875784.
    Abstract:
    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.
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