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Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for KATP channel.

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.

journal_name

Life Sci

journal_title

Life sciences

authors

Gooshe M,Tabaeizadeh M,Aleyasin AR,Mojahedi P,Ghasemi K,Yousefi F,Vafaei A,Amini-Khoei H,Amiri S,Dehpour AR

doi

10.1016/j.lfs.2016.11.006

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

38-46

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(16)30637-3

journal_volume

168

pub_type

杂志文章

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Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for KATP channel.