Effects of S20749, a close analogue of sumatriptan, on porcine carotid haemodynamics and human isolated coronary artery.
Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT1D receptor agonists, have the ability to constrict porcine arteriovenous anastomoses. Sumatriptan also constricts the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of S20749 (1-[2-(dimethylamino)ethyl]-naphthalene-7-methylsulfonamide), a close analogue of sumatriptan. S20749 (30, 100, 300 and 1000 micrograms.kg-1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was moderately increased. These changes were statistically significant with the highest two doses. S20749 moderately constricted the human isolated coronary artery (pD2: < or = 4.5: Fmax: > 11% of the contraction to 100 mM K+). The above results suggest that S20749 should be able to abort migraine headaches in patients.
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Dutch Migraine Research Group, The Netherlands.
P R
PR
Saxena
A
A
Maassen vandenBrink
J P
JP
Heiligers
E
E
Scalbert
B G
BG
Lemaitre
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D012039:Regional Blood Flow; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D009281:Naphthalenes; C104309:S 20749; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D018170:Sumatriptan