Interaction of a potential antimigraine drug (Org GC 94) with the vasomotor action of serotonin

The interaction of a potential anti-migraine drug (Org GC 94) with the vasomotor action of 5-HT in vitro in feline, canine and human intra- and extracranial arteries, as well as in vivo in the canine nasal vascular bed has been investigated. In the two in vitro preparations, i.e. using superfusion or bath techniques, the intracranial vessels were more sensitive to 5-HT vasoconstriction than the extracranial ones. As both the maximum contraction and the slope of the dose-response curves were reduced by increasing concentrations of Org GC 94, the antagonism of 5-HT did not involve competitive blockade of 5-HT receptors. The dilator response was tested in arteries brought to a higher tone with prostaglandin F 2α. 5-HT produced a dose-dependent dilatation which, like the vasoconstriction, was antagonized in a non-competitive manner by Org GC 94. Intra-arterial injections of 5-HT provoked nasal vasoconstriction and this response was clearly potentiated by Org GC 94 in low doses while higher doses inhibited the vascular response to 5-HT. The specific effect of Org GC 94 in vivo may be the potentiation of 5-HT-induced vasoconstriction. The hypothesis is discussed that the so-called anti-5-HT agents act in migraine patients as partial agonist of 5-HT, mimicking rather than antagonizing 5-HT.