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Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

Authors Knapp L, Szita B, Kocsis K, Vécsei L, Toldi J

Received 13 July 2016

Accepted for publication 29 September 2016

Published 20 December 2016 Volume 2017:11 Pages 27—34

DOI https://doi.org/10.2147/DDDT.S117166

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rammohan Devulapally

Peer reviewer comments 3

Editor who approved publication: Professor Manfred Ogris

Levente Knapp,1 Bence Szita,1 Kitti Kocsis,1,2 László Vécsei,2,3 József Toldi1,2

1Department of Physiology, Anatomy, and Neuroscience, University of Szeged, 2MTA-SZTE Neuroscience Research Group, 3Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary

Background: The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified.
Materials and methods: In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested.
Results: The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level.
Discussion: The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.

Keywords: migraine, cortical spreading depression, nitroglycerin, sumatriptan, kynurenic acid analogues

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Other article by this author:

Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood–brain barrier permeability

Oláh G, Herédi J, Menyhárt Á, Czinege Z, Nagy D, Fuzik J, Kocsis K, Knapp L, Krucsó E, Gellért L, Kis Z, Farkas T, Fülöp F, Párdutz Á, Tajti J, Vécsei L, Toldi J

Drug Design, Development and Therapy 2013, 7:981-987

Published Date: 16 September 2013