Influence of pizotifen and ergotamine on the venoconstrictor effect of 5-hydroxytryptamine and noradrenaline in man

The influence of locally infused pizotifen (80 ng) and ergotamine (16 ng and 4 ng) on the compliance of superficial hand veins in man, and their interactions with the venoconstrictor effects of noradrenaline and 5-hydroxytryptamine (5-HT), were investigated in a placebo-controlled study in healthy volunteers. Pizotifen alone reduced venous compliance and produced a parallel displacement to the right of the 5-HT dose-response curve suggestive of competitive antagonism. The venoconstrictor effect of noradrenaline was not influenced by pizotifen. This confirms the selective antagonism of 5-HT by pizotifen and supports the existence of specific 5-HT receptors on human veins. After infusion of 16 ng ergotamine, which by itself reduced venous compliance, the venoconstrictor effects of the lower doses of 5-HT and of all doses of noradrenaline were larger but still never exceeded the arithmetic sum of the separate effects of noradrenaline or 5-HT and ergotamine. A lower dose of ergotamine (4 ng) induced only a small venoconstriction and did not influence the constrictor effect of noradrenaline. Therefore, in contrast to previous observations, no potentiation of the venoconstrictor effect of noradrenaline by ergotamine was observed under the present experimental conditions. The additive effect of noradrenaline and ergotamine may well explain its therapeutic action in the treatment of migraine.