Effects of alniditan on neurogenic oedema in the rat dura mater and on contraction of rat basilar artery.
The non-indole 5-HT receptor agonist, alniditan (R 91274), was tested and compared to sumatriptan in an in vivo model of neurogenic inflammation within the meninges of rats and in rat basilar artery in a Mulvany-Halpern chamber in vitro. Alniditan dose dependently attenuated the neurogenic inflammation and was more potent than sumatriptan. The alniditan response was blocked by the 5-HT(1B/D) receptor antagonist, GR 127935 (2'-methyl-4'-(5-methyl-[1,2, 4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide), but not by ketanserin, indicating that the effect is mediated through 5-HT(1B/D) receptors. Alniditan did not attenuate substance P-induced inflammation, suggesting that the mediating receptors are located prejunctionally. In vitro alniditan exhibited less vasoconstrictive effects on the rat basilar artery than did sumatriptan, although at a very high concentration (1 mM), alniditan caused intensive constriction, most likely through a mechanism independent from 5-HT receptor activation.
Limmroth
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Department of Neurology, University Hospital, University of Essen, Hufelandstrasse 55, 45147, Essen, Germany. volker.limmroth@t-online.de
Bischoff
A
A
Fetscher
C
C
Wermelskirchen
D
D
Diener
H
H
Michel
M C
MC
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology*; D001929:Brain Edema / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000187:drug effects* / Q000473:pathology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001578:Benzopyrans; D010069:Oxadiazoles; D010879:Piperazines; D011437:Propylamines; D011743:Pyrimidines; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; C090701:GR 127935; D012701:Serotonin; D013373:Substance P; D018170:Sumatriptan; D007650:Ketanserin; C100822:alniditan