Pizotifen, an antimigraine drug with venoconstrictor activity in vivo

Determination of the diameter of saphenous veins in conscious dogs revealed a considerable agonist activity of pizotifen not only after local but also after systemic i.v. and oral administration. By contrast, stimulation of vascular smooth muscle in vitro occurred only at very high concentrations (greater than 1 mumol/l). Treatment of dogs with 30 micrograms/kg ketanserin i.v. produced a two-fold shift to the right of the dose-response curve of locally infused 5-hydroxytryptamine (5-HT) but increased only slightly the ED50 of locally infused pizotifen. Furthermore, pizotifen proved to be a highly selective 5-HT receptor blocking agent both in vivo (on saphenous veins) and in vitro (on saphenous veins and basilar arteries) from dogs and humans. By contrast, antagonism of responses to both noradrenaline and CaCl2 occurred only at about 100 times higher pizotifen concentrations than required for blockade of 5-HT effects. It is suggested that the clinical effectiveness of pizotifen in migraine prophylaxis derives at least in part from an agonist activity the mechanism of which remains to be elucidated.