Biphasic effect of sumatriptan on PTZ-induced seizures in mice: Modulation by 5-HT1B/D receptors and NOS/NO pathway.

Autor: Gooshe M; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran; Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran., Ghasemi K; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran., Rohani MM; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran., Tafakhori A; Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran., Amiri S; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran., Aghamollaii V; Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran; Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran., Ahmadi M; Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran., Dehpour AR; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Dehpour@yahoo.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2018 Apr 05; Vol. 824, pp. 140-147. Date of Electronic Publication: 2018 Feb 02.
DOI: 10.1016/j.ejphar.2018.01.025
Abstrakt: Sumatriptan has been among the top choices in the management of migraine headaches. The association between migraine and epilepsy highlights the possible effect of sumatriptan on seizures. In this regard, we investigated sumatriptan effects on PTZ-induced seizures thresholds and delineated the modulatory role of 5-HT1B/D receptors and NOS/NO pathway. Our data revealed the anti-convulsant effects of lower doses of sumatriptan, and pro-convulsant effects of higher doses of sumatriptan. GR 127935, a selective 5-HT1B/D antagonist, could abolish the sumatriptan anti-convulsant effects, but it was ineffective against the sumatriptan pro-convulsant effects. Serotonin depletion by consecutive administration of p-CPA, a selective irreversible inhibitor of tryptophan hydroxylase, could not affect the anti-convulsant effects of sumatriptan. The anti-convulsant effects of sumatriptan was potentiated by L-NAME, a non-selective NOS inhibitor, 7-NI, a selective nNOS inhibitor, but not AG, an iNOS inhibitor. It was also neutralized by L-ARG, a NO precursor. The pro-convulsant effects of sumatriptan were blocked by L-NAME and AG, but not 7-NI. It was also potentiated by L-ARG. Our data revealed that anti-convulsive effects of sumatriptan is mediated by interaction between non-serotonergic 5-HT1B/D receptors and nNOS/NO pathway. Besides, the pro-convulsive effect of sumatriptan is mediated by iNOS/NO pathway independent of 5-HT1B/D receptors. For the first time, this study reported the biphasic effect of sumatriptan on an animal model of GCS and its modulatory pathways.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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