Characterization of 5-hydroxytryptamine receptors in the cranial vasculature.

The availability of selective compounds has made it possible to subdivide 5-hydroxytryptamine (5-HT) receptors into three distinct types, called 5-HT1-like, 5-HT2 and 5-HT3. The selective agonists at the three receptor types are, respectively, 5-carboxamidotryptamine, alpha-methyl-5-HT and 2-methyl-5-HT. While no selective antagonists are yet available for the 5-HT1-like receptors, some compounds, including ketanserin and MDL 72222, selectively antagonize 5-HT2 and 5-HT3 receptors respectively. Depending upon experimental conditions, 5-HT causes a constriction or dilatation of cerebral and extracerebral cranial vessels. Vascular contraction by 5-HT seems to be mediated primarily via 5-HT2 receptors (located mainly on large conducting vessels), though in several instances (for example, dog and human basilar arteries and porcine arteriovenous anastomoses; AVAs) 5-HT1-like receptors are involved in addition to or in place of 5-HT2 receptors. In the rabbit ear and external carotid arteries 5-HT may act directly on alpha-adrenoceptors. Arteriolar dilatation, leading to increased capillary ("nutrient") blood flow, occurs via 5-HT1-like receptors. However, the 5-HT1-like receptors on the arterioles and AVAs appear to be similar but not identical. Since a reduction of plasma 5-HT and opening of AVAs have been implicated in the pathophysiology of migraine, compounds acting on 5-HT1-like receptors to close the shunt vessels can be expected to have therapeutic activity in migraine.