title: The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan.
abstract: The mechanistically novel benzopyran derivative SB-220453, which is undergoing clinical evaluation in migraine, exhibits a high affinity for a selective, but not yet characterized, binding site in the human brain. It inhibits nitric oxide release and cerebral vasodilatation following cortical spreading depression as well as carotid vasodilatation induced by trigeminal nerve stimulation in the cat. The aim of our study was to investigate the contractile properties of SB-220453 on a number of human isolated blood vessels (coronary artery, saphenous vein and middle meningeal artery) as well as atrial and ventricular cardiac trabeculae. While sumatriptan induced marked contractions in three blood vessels investigated, SB-220453 was devoid of any effect. In atrial and ventricular cardiac trabeculae, neither SB-220453 nor sumatriptan displayed a positive or negative inotropic effect. Since SB-220453 did not contract the middle meningeal artery, we conclude that potential anti-migraine effects are not mediated via a direct cerebral vasoconstriction. The lack of activity of SB-220453 in coronary artery, saphenous vein and cardiac trabeculae demonstrates that the compound is unlikely to cause adverse cardiac side-effects.
authors.affiliation: Department of Pharmacology, Erasmus University Medical Centre Rotterdam EMCR, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: MaassenVanDenBrink
authors.forename: R W
authors.initials: RW
authors.lastname: van den Broek
authors.forename: R
authors.initials: R
authors.lastname: de Vries
authors.forename: N
authors.initials: N
authors.lastname: Upton
authors.forename: A A
authors.initials: AA
authors.lastname: Parsons
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology* / Q000633:toxicity; D001578:Benzopyrans / Q000494:pharmacology* / Q000633:toxicity; D003331:Coronary Vessels / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects; D018170:Sumatriptan / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000700:Analgesics; D001549:Benzamides; D001578:Benzopyrans; C118706:tonabersat; D018170:Sumatriptan; D009638:Norepinephrine