Effect of sumatriptan, a selective 5-HT1-like receptor agonist, on pial vessel diameter in anaesthetised cats.
The action of sumatriptan, a selective 5-HT1-like receptor agonist that is effective for the acute treatment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10 microM), when microinjected perivascularly, caused a decrease in pial artery diameter (maximum change of -19 +/- 9%; mean +/- SD) but had no effect on the diameter of pial veins. Sumatriptan (1 microM)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (1 microM) or ondansetron (1 microM) but was significantly (p less than 0.01) attenuated by methiothepin (1 microM). Intravenous infusion of a clinically effective dose of sumatriptan (64 micrograms/kg/10 min) caused selective carotid vasoconstriction (22 +/- 6% increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (1 microM) administered perivascularly in these animals before and after the infusion caused pial artery vasoconstriction. These results demonstrate that perivascularly administered sumatriptan causes pial artery vasoconstriction via activation of 5-HT1-like receptors. However, intravenously administered sumatriptan does not cause pial artery vasoconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.
Connor
H E
HE
Department of Neuropharmacology, Glaxo Group Research Ltd., Hertfordshire, U.K.
Stubbs
C M
CM
Feniuk
W
W
Humphrey
P P
PP
D000818:Animals; D001692:Biological Transport; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D002550:Cerebral Veins / Q000187:drug effects*; D005260:Female; D006706:Homeostasis; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011985:Receptors, Serotonin / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D018170:Sumatriptan; D014661:Vasoconstriction / Q000187:drug effects
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D008719:Methiothepin; D018170:Sumatriptan