DIFFERENTIAL DISTRIBUTION OF 5HT(1D)-IMMUNOREACTIVITY AND 5HT(1B)-IMMUNOREACTIVITY WITHIN THE HUMAN TRIGEMINO-CEREBROVASCULAR SYSTEM - IMPLICATIONS FOR THE DISCOVERY OF NEW ANTIMIGRAINE DRUGS

Sumatriptan, a 5HT(1B/1D)-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT(1 B)-receptor mediated response). The antimigraine activity of sumatript an may also result from inhibition of the release of vasoactive neurop eptides from trigeminal sensory fibres within the meninges. The identi ty of the 5HT(1B/1D)-receptor subtype mediating this effect is unknown . Using 5HT(1D)- and 5HT(1B)-receptor-specific antibodies we have demo nstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT(1B)-receptor pro tein was detected on dural arteries. In contrast, only 5HT(1D)-recepto r protein was detected on trigeminal sensory neurones including periph eral and central projections to dural blood vessels and to the medulla . Within the medulla 5HT(1D)-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings h ave important implications for the design of new antimigraine drugs.