[Mechanism of action of drugs currently used in the prevention of migraine].

The mode of action of some classical and newer drugs used in the preventive interval treatment of migraine is discussed in the light of a modern theory of the pathogenesis of migraine headache. This headache is produced when two elements--a passive distension of the extracranial arteries and a lowering of the pain threshold of the receptors situated in the walls of the affected vessels--are present simultaneously. The main humoral factors involved in this phenomenon are plasma-kinins, serotonin and--to a lesser degree--histamine. The role played by serotonin which is released by the blood platelets at the onset of the attack is twofold: on the one hand, free serotonin increases the permeability of the capillaries, favouring transudation of plasmakinins, and lowers the pain threshold, while on the other hand, its increased excretion causes a secondary reduction in its plasma concentration, promoting hypotonicity of the extracranial vessels. Among the substances used for prophylactic interval treatment, some, such as dihydroergotamine, clonidine and the beta-blocking agents have a purely vascular site of action, maintaining--by various mechanisms--the tone of the extracranial arteries and thus reducing their lability. Methysergide and pizotifene have a chiefly indirect effect on the vessels, by potentiating the effect of catecholamines or helping to maintain free serotonin at a certain level. They act primarily against the humoral elements responsible for lowering the pain threshold: methysergide by inhibiting the release and blocking the effects of serotonin, by countering the potentiating effect of serotonin on the pain induced by plasmakinins and by inhibiting histamine release; pizotifene by inhibiting the release and blocking the effects of histamine, by blocking the effects of serotonin and by slightly inhibiting the peripheral effects of plasmakinins. Thus, the multifactorial pathogenesis of migraine helps to explain the effectiveness against migraine of substances possessing the most varied pharmacodynamic profiles.