The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

Abstract

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. 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). 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.). 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). 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. GR43175 (100 μg kg−1) decreased bradykinin (10 μmol kg−1)‐induced extravasation from 142 to 115% above vehicle‐treated animals (P < 0.05). 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.