The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan

The mechanistically novel benzopyran derivative SB-220453, which is undergo ing clinical evaluation in migraine, exhibits a high affinity for a selecti ve, but not yet characterized, binding site in the human brain. It inhibits nitric oxide release and cerebral vasodilatation following cortical spread ing depression as well as carotid vasodilatation induced by trigeminal nerv e stimulation in the cat. The aim of our study was to investigate the contr actile properties of SE-220453 on a number of human isolated blood vessels (coronary artery, saphenous vein and middle meningeal artery) as well as at rial and ventricular cardiac trabeculae. While sumatriptan induced marked c ontractions in three blood vessels investigated, SB-220453 was devoid of an y effect. In atrial and ventricular cardiac trabeculae, neither SB-220453 n or sumatriptan displayed a positive or negative inotropic effect. Since SB- 220453 did not contract the middle meningeal artery, we conclude that poten tial anti-migraine effects are not mediated via a direct cerebral vasoconst riction. The lack of activity of SB-220453 in coronary artery, saphenous ve in and cardiac trabeculae demonstrates that the compound is unlikely to cau se adverse cardiac side-effects.