The novel anti-migraine agent rizatriptan inhibits neurogenic dural vasodilation and extravasation.
These studies in anaesthetised rats showed, using intravital microscopy, that the novel anti-migraine agent, rizatriptan, significantly reduced electrically stimulated dural vasodilation but had no effect on increases in dural vessel diameter produced by exogenous substance P or calcitonin gene-related peptide (CGRP). Rizatriptan also significantly inhibited dural plasma protein extravasation produced by high intensity electrical stimulation of the trigeminal ganglion. We suggest that rizatriptan inhibits the release of sensory neuropeptides from perivascular trigeminal nerves to prevent neurogenic vasodilation and extravasation in the dura mater. These prejunctional inhibitory effects may be involved in the anti-migraine action of rizatriptan.
Williamson
D J
DJ
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Shepheard
S L
SL
Hill
R G
RG
Hargreaves
R J
RJ
D000704:Analysis of Variance; D000818:Animals; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology; D008881:Migraine Disorders / Q000188:drug therapy; D009469:Neuromuscular Junction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014278:Trigeminal Nuclei / Q000187:drug effects / Q000502:physiology; D014363:Tryptamines; D014664:Vasodilation / Q000187:drug effects*
D001798:Blood Proteins; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; D013373:Substance P; C093622:rizatriptan; D015740:Calcitonin Gene-Related Peptide