Charles Q. Meng Pages 385 - 404 ( 20 )
Migraine is a common disorder severely affecting normal life. There is no perfect treatment for it to date. Sumatriptah is the first, antimigraine drug developed, through contemporary medicinal chemistry.· Since sumatriptan binds with high affinity to 5-HT1Da, 5-HT1Db and 5-HT1F receptors it has been proposed that one or more of these receptor sub types is involved in the pathophysiology of migraine. It is almost certain that the 5-HT1D receptor causes the cardiac adverse reactions of sumatriptan.
Several compounds are currently under clinical development or about to reach the market for the treatment of migraine. However, most of them are structurally similar to sumatriptan, bind to the 5- HT10 receptor and therefore have potential cardiac adverse reactions. An obvious advantage of some of the compounds over sumatriptan is the higher oral bioavailability than sumatriptan. Some penetrate the CNS whereas sumatriptan does not. It remains to be seen whether CNS penetration is beneficial.
Vascular and neurogenic mechanisms have -been proposed for migraine. Both theories are backed up by scientific data and countered by controversies.
Selective ligands at the respective 5-HT 1Da· 5-HT1D and 5-HT1F rceptors will possibly provide not only scientific tools for migraine research but also satisfactory antimigraine drugs.