[Anti-migraine drug sumatriptan succinate, a 5-HT1B/1D-receptor agonist].
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.
Iwasawa
Y
Y
Education & Training Office, Research Division, GlaxoSmithKline KK, 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan.
Danjo
T
T
D000818:Animals; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018170:Sumatriptan / Q000494:pharmacology* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use
D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D018170:Sumatriptan