Sumatriptan succinate (SMT) was a highly specific 5-HT1-receptor agonist. It showed high affinity only for
5-HT but no affinity for other
neurotransmitter receptors such as
muscarinic,
dopamine D1, D2,
adrenergic alpha 1, alpha 2, and beta. Furthermore, it was highly selective for 5-HT1B/1D-receptor and showed no affinity for 5-HT2 and 5-HT3 receptors. SMT contracted isolated cranial arteries such as basilar, midcerebral, temporal arteries and large arteries in the dura matter, but did not contract coronary, femoral, mesenteric and other arteries. Reflecting these results, SMT induced vasoconstriction of carotid artery, but produced practically no contractile responses in the other arteries mentioned above in anaesthetized animals. These pharmacological characteristics of SMT were different from those of
ergot alkaloids, current anti-
migraine drugs, which contracted coronary, femoral and other arteries as well. SMT inhibited
neurotransmitter release, including CGRP, from trigeminal nerve terminals. Consequently
protein extravasation induced by CGRP was inhibited and
neurogenic inflammation could be suppressed. It was believed that SMT showed its anti-
migraine activity through cranial vasoconstriction via 5-HT1B/1D receptors, since it did not show any
analgesic activities. Its clinical efficacy on
migraine and
cluster headache had been already confirmed in about 100 western countries. Its efficacy was also shown by open trials and placebo controlled double blind tests in Japan.