| Autor: |
Johnson KW; Neuroscience Research and Discovery Chemistry Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA. JOHNSON_KIRK_W@Lilly.Com, Nelson DL, Dieckman DK, Wainscott DB, Lucaites VL, Audia JE, Owton WM, Phebus LA |
| Jazyk: |
angličtina |
| Zdroj: |
Cephalalgia : an international journal of headache [Cephalalgia] 2003 Mar; Vol. 23 (2), pp. 117-23. |
| DOI: |
10.1046/j.1468-2982.2003.00464.x |
| Abstrakt: |
The compound m-chlorophenylpiperazine (mCPP), which is known to trigger migraine-like head pain in some subjects, was evaluated for its ability to induce dural plasma protein extravasation (PPE) in guinea pigs. Intravenous mCPP dose-dependently increased PPE. This effect was inhibited by non-selective 5-HT2 receptor antagonists (methysergide, LY53857, LY215840), by a peripherally restricted 5-HT2 receptor antagonist (xylamidine) and by a 5-HT2B selective receptor antagonist (LY202146). These data suggests that peripheral 5-HT2B receptors mediate mCPP-induced PPE. The nitric oxide synthase inhibitor L-NAME and 5-HT1 agonist sumatriptan also blocked mCPP-induced PPE, suggesting a role for nitric oxide (NO) and the trigeminal system, respectively. NO release has been linked to activation of the 5-HT2B receptor on the vascular endothelium. However, LY202146 did not block PPE induced by electrical stimulation of the trigeminal ganglion. These data are consistent with activation of peripheral 5-HT2B receptors initiating PPE and the theory that selective 5-HT2B antagonists might be effective prophylactic therapies for migraine. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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