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

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 t...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Knapp Levente
Szita Bence
Kocsis Kitti
Vécsei László
Toldi József
Dokumentumtípus: Cikk
Megjelent: 2017
Sorozat:DRUG DESIGN DEVELOPMENT AND THERAPY 11
doi:10.2147/DDDT.S117166

mtmt:3163480
Online Access:http://publicatio.bibl.u-szeged.hu/12704
Leíró adatok
Tartalmi kivonat: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. © 2017 Knapp et al.
Terjedelem/Fizikai jellemzők:27-34
ISSN:1177-8881