Monthly Update: Central & Peripheral Nervous Systems: Pharmacology of antimigraine 5-HT1Dreceptor agonists

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Abstract
The 5-HT 1D receptor agonist sumatriptan is undoubtedly a significant advance in the management of migraine and cluster attacks. Notwithstanding, sumatriptan has some important shortcomings, which include low oral bioavailability, headache recurrence (possibly due to short t1/2) and contraindication in patients with coronary artery disease. These shortcomings, as well as lofty sales potentials, have stimulated the search and design of second-generation 5-HT1D receptor agonists. The large list of such compounds is growing, but those that are likely to be marketed in this millennium include: zolmitriptan, MK-462, naratriptan, BMS-180048 and, perhaps, the non-indole derivative alniditan. However, none of the newer 5-HT1D receptor agonists, as is also the case with sumatriptan, shows selectivity towards either the 5-HT1Dα or the 5-HT1Dβ receptor subtype and there seems to be little qualitative difference in their pharmacological profiles. Thus, these compounds suppress adenylyl cyclase activity, contract isolated cerebral (e.g., human, bovine or canine middle cerebral artery) as well as, though weakly, some peripheral arteries (e.g., human coronaries), reduce carotid artery blood flow in the cat, dog or pig by a selective action on arteriovenous anastomoses, and inhibit dural plasma extravasation (rat) and evoked potentials in dorsal horn neurones (cat) following trigeminal ganglion stimulation. Human brachial arteriovenous anastomoses are also constricted by sumatriptan. The newer 5-HT1D receptor agonists appear to offer some advantage over sumatriptan with respect to bioavailability, onset of action or headache recurrence.