title: Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Anatomy, and Neuroscience, University of Szeged.
authors.forename: Levente
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Department of Physiology, Anatomy, and Neuroscience, University of Szeged.
authors.forename: Bence
authors.initials: B
authors.lastname: Szita
authors.affiliation: Department of Physiology, Anatomy, and Neuroscience, University of Szeged; MTA-SZTE Neuroscience Research Group.
authors.forename: Kitti
authors.initials: K
authors.lastname: Kocsis
authors.affiliation: MTA-SZTE Neuroscience Research Group; Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Physiology, Anatomy, and Neuroscience, University of Szeged; MTA-SZTE Neuroscience Research Group.
authors.forename: József
authors.initials: J
authors.lastname: Toldi
mesh_terms: D013181:Cortical Spreading Depression / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007274:Injections, Intraperitoneal; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008881:Migraine Disorders / Q000188:drug therapy*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D018170:Sumatriptan / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D018170:Sumatriptan; D005996:Nitroglycerin; D007736:Kynurenic Acid
keywords: cortical spreading depression; kynurenic acid analogues; migraine; nitroglycerin; sumatriptan