Possible role of alpha-adrenoceptor subtypes in acute migraine therapy

Even though the underlying mechanisms for the pathophysiology of migraine attacks are not completely understood, little doubt exists that the headache phase is explained by dilatation of cranial, extracerebral blood vessels. In this context, experimental models predictive for anti-migraine activity have shown that both triptans and ergot alkaloids, which abort migraine headache, produce vasoconstriction within the carotid circulation of different species. In contrast to the well-established role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT1B receptors in the common carotid vascular bed, the role of alpha-adrenoceptors and their subtypes has been examined only relatively recently. Using experimental animal models and alpha1- and alpha2-adrenoceptor agonists (phenylephrine and BHT933, respectively) and antagonists (prazosin and rauwolscine, respectively), it was shown that activation of either receptor produces a cranioselective vasoconstriction. Subsequently, investigations employing relatively selective antagonists at alpha1- (alpha1A, alpha1B, alpha1D) and alpha2- (alpha2A, alpha2B, alpha2C) adrenoceptor subtypes revealed that specific receptors mediate the carotid haemodynamic responses in these animals. From these observations, together with the potential limited role of alpha1B- and alpha2C-adrenoceptors in the regulation of systemic haemodynamic responses, it is suggested that selective agonists at these receptors may provide a promising novel avenue for the development of acute anti-migraine drugs.