Author/Editor     Buzzi, MG; Bonamini, M
Title     Inhibition of trigeminal afferents by antimigraine drugs
Type     članek
Source     In: Pogačnik T, Žvan B, editors. Current views on headache. Proceedings of the joint meeting Italy - Slovenia; 1994 Febr 11-12. Ljubljana: University medical centre,
Publication year     1994
Volume     str. 86-8
Language     eng
Abstract     Investigation on the mechanism of action of antimigraine drugs such as sumatriptan and dihydroergotamine and other ergot derivatives supports the belief that a possible pathogenetic mechanism for migraine attacks is represented by aclivation of trigemino-vascular fibers in the dura mater. Both sumatriptan and dihydroergotamine are able to contract blood vessels. However, this activity does not seem to be relevant for their efficacy in aborting migraine pain. Experimental and clinical observation exist to suggest that the above drugs act with a prejunctional mechanism via activation of serotonin receptors on trigeminal sensory fibers. Pharmacological observations that serotonin (5-HT) agonists with selectivity for the D-lype receptor block neurogenic inflammation (i.e., vasodilatation and plasma protein leakage) in rat dura mater induced by clectrical stimulation of the trigeminal ganglion (ETGS), support the hypothesis that neurogenic inflammation is relevant to the palhophysiology of migraine and cluster headaches. Experimental evidences support the conclusion that 5-HT heteroreceptors are localed on neuropeptide containing unmyelinated sensory C-fibers. Prejunctional mechanisms and inhibition of neuropeptide release from C-fibers surrounding blood vessels mediate drug blockade of plasma protein extravasation within dura mater. Sumatriptan and dihydroergotamine, the most effective drugs in treating migraine or cluster headache attacks, are inaclive when tested against concentrations of substance P or neurokinin A, which cause plasma leakage when administered intravenously. Sumatriplan is also inactive against leakage caused hy alpha-methyl S-HT, a 5-HT2 agonist that stimulates endothelial cell leakage directly. Protein leakagc caused by alpha-methyl 5-HT is blocked by pretreatment with pimozide, a 5-HT2 agonist.(trunc.)
Descriptors     MIGRAINE
TRIGEMINAL NERVE