Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for K<inf>ATP</inf> channel

Amini-Khoei, H. and Gooshe, M. and Aleyasin, A.R. and Tabaeizadeh, M. and Mojahedi, P. and Ghasemi, K. and Yousefi, F. and Vafaei, A. and Amiri, S. and Dehpour, A.R. (2017) Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for K<inf>ATP</inf> channel. Life Sciences, 168. pp. 38-46.

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Abstract

Aims Although approving new anticonvulsants was a major breakthrough in the field of epilepsy control, so far we have met limited success in almost one third of patients suffering from epilepsy and a definite and reliable method is yet to be found. Levosimendan demonstrated neuroprotective effects and reduced mortality in conditions in which seizure can be an etiology of death; however, the underlying neuroprotective mechanisms of levosimendan still eludes us. In the light of evidence suggesting levosimendan can be a KATP channel opener and nitrergic pathway activator, levosimendan may exert antiseizure effects through KATP channels and nitrergic pathway. Main methods In this study, the effects of levosimendan on seizure susceptibility was studied by PTZ-induced seizures model in mice. Key findings Administration of a single effective dose of levosimendan significantly increased seizures threshold and the nitrite level in the hippocampus and temporal cortex. Pretreatment with noneffective doses of glibenclamide (a KATP channel blocker) and L-NAME (a non-selective NOS inhibitor) neutralize the anticonvulsant and nitrite elevating effects of levosimendan. While 7-NI (a neural NOS inhibitor) blocked the anticonvulsant effect of levosimendan, Aminoguanidine (an inducible NOS inhibitor) failed to affect the anticonvulsant effects of levosimendan. Cromakalim (a KATP channel opener) or L-arginine (an NO precursor) augmented the anticonvulsant effects of a subeffective dose of levosimendan. Moreover, co-administration of noneffective doses of Glibenclamide and L-NAME demonstrated a synergistic effect in blocking the anticonvulsant effects of levosimendan. Significance Levosimendan has anticonvulsant effects possibly via KATP/nNOS/NO pathway activation in the hippocampus and temporal cortex

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: KATP channels, Levosimendan, Nitrergic system, PTZ, Seizure
Subjects: QV pharmacology
QV pharmacology > QV 752 Pharmacognosy
Divisions: Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: zahra bagheri .
Date Deposited: 15 Jun 2017 17:39
Last Modified: 19 Jun 2017 09:34
URI: http://eprints.skums.ac.ir/id/eprint/228

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