Sumatriptan and venoconstriction.

The paper by MB Vincent et 31. in this issue represents a further piece of investigation on the mechanism of action of sumatriptan. It focuses on the efficacy of the drug in aborting cluster headache ( CHj attacks, a clinical condition for which sumatriptan is highly effective and now represents the treatment of choice. The authors have chosen porcine ophthalmic artery ( POAj for evaluating the vascular effects of sumatriptan, since CH is characterized by marked ocular circulatory abnormalities. Therefore, the in vitro experimental model results in a reliable method for characterizing the activity of sumatriptan on ocular vessels. The drug was tested on CGRPand VIP-induced P O A relaxation, the results indicating that the drug is unable to inhibit CGRP-induced relaxation. Activation of peripheral trigeminal fibers has been proposed as a possible pathogenetic mechanism for migraine and CH attacks. Such depolarization induces vasodilatation and plasma protein leakage (neurogenic inflammation) through the release of vasodilatatory and permeability promoting peptides (CGRP and SP). Based on previous findings and on the data reported in this paper, sumatriptan seems not to act via a vasoconstrictor mechanism. A neuronal, prejunctional mechanism via autoreceptors on trigeminal fibers appears more likely. The authors also report that sumatriptan inhibits VIP-induced relaxation. The discussion on this finding is focused on the possible secondary activation of parasympathetic fibers releasing VIP during CH attacks. Relaxation induced by VIP is known to be endothelium-independent and to act via cyclic AMP. Sumatriptan inhibits cyclic A M P accumulation in canine saphenous vein. These pharmacological properties may well explain why sumatriptan inhibits VIP-induced relaxation. The paper by MB Vincent et al. offers an interesting model for further studies on the relevance of autonomic responses during CH attacks and on different mechanisms of action of sumatriptan on such a complex clinical condition.