Recent developments in 5-HT(1D) agonists.

Since the discovery of sumatriptan, several 5-HT(1D/1B) receptor agonists have now reached the clinic and marketplace as treatments for migraine. The highly efficacious F-11356 is the latest compound to emerge but none of these agents have appreciable selectivity between the h5-HT(1D) and h5-HT(1B) receptor subtypes. Research has now focused on obtaining selective h5-HT(1D) receptor agonists which, if inhibition of peptide release is involved in the antimigraine action, may be expected to have reduced vasoconstrictor liability. This has led especially to the discovery of L-775606 and PNU-109291, which should constitute useful tools to delineate the role of h5-HT(1D) receptors in migraine.