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 c ompared to sumatriptan in an in vivo model of neurogenic inflammation withi n the meninges of rats and in rat basilar artery in a Mulvany-Halpern chamb er in vitro. Alniditan dose dependently attenuated the neurogenic inflammat ion and was more potent than sumatriptan. The alniditan response was blocke d by the 5-HT1B/D, receptor antagonist, GR 127935 (2'-methyl-4'-(5-methyl-[ 1,2,4]oxadiazol-3-yl)-bipenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-pipe razin-1 -yl)-phenyl]-amide), but not by ketanserin, indicating that the eff ect is mediated through 5-HT1B/D receptors. Alniditan did not attenuate sub stance 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 l ikely through a mechanism independent from 5-HT receptor activation. (C) 19 99 Elsevier Science B.V. All rights reserved.