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The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater
Author(s) -
Buzzi M. Gabriella,
Moskowitz Midiael A.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14679.x
Subject(s) - extravasation , substance p , neurogenic inflammation , trigeminal ganglion , dura mater , bradykinin , sumatriptan , capsaicin , evans blue , endocrinology , medicine , blood–brain barrier , albumin , chemistry , stimulation , anesthesia , agonist , receptor , neuropeptide , anatomy , pathology , central nervous system , biology , sensory system , neuroscience
1 We describe the actions of GR43175, a 5‐hydroxytryptamine 1 (5‐HT 1 )‐like receptor agonist, on neurogenically‐mediated plasma protein extravasation within an important pain‐sensitive intracranial tissue, the dura mater. 2 GR43175 markedly attenuated extravasation of 125 I‐albumin from blood vessels within ipsilateral dura mater when administered to rats (100 μg kg −1 ) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min.); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P < 0.005). 3 GR43175 (100 μg kg −1 , i.v., rats; 30 μg kg −1 , i.v., guinea‐pigs) decreased the leakage of radiolabeled albumin from 163% to 119% ( P < 0.005, guinea‐pig) or from 174 to 118% ( P < 0.05, rat) above vehicle‐treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 μmol kg −1 , i.v.). 4 GR43175 (30–300 μg kg −1 ) did not block plasma protein extravasation within extracranial tissues of rats and guinea‐pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5 The protein leakage which followed the i.v. administration of 5‐HT (1 μmol kg −1 ) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg −1 or 1 nmol kg −1 ) and neurokinin A (1 nmol kg −1 ), was not blocked by GR43175 (100, 300 μg kg −1 ) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation. 6 GR43175 (100 μg kg −1 ) decreased bradykinin (10 μmol kg −1 )‐induced extravasation from 142 to 115% above vehicle‐treated animals ( P < 0.05). 7 These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.