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

Levente Knapp, Bence Szita, Kitti Kocsis, L. Vécsei, József Toldi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalDrug Design, Development and Therapy
Volume11
DOIs
Publication statusPublished - 2017

Fingerprint

Cortical Spreading Depression
Kynurenic Acid
Sumatriptan
Nitroglycerin
Migraine Disorders
Theoretical Models
Preclinical Drug Evaluations
Neurotransmitter Agents
Research Design
Pharmaceutical Preparations

Keywords

  • Cortical spreading depression
  • Kynurenic acid analogues
  • Migraine
  • Nitroglycerin
  • Sumatriptan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Nitroglycerin enhances the propagation of cortical spreading depression : Comparative studies with sumatriptan and novel kynurenic acid analogues. / Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, L.; Toldi, József.

In: Drug Design, Development and Therapy, Vol. 11, 2017, p. 27-34.

Research output: Contribution to journalArticle

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