In vivo effects of sumatriptan (GR 43175) on extracellular levels of 5-HT in the guinea pig.
The effect of sumatriptan, a selective 5-HT1D receptor agent, on extracellular levels of 5-HT in the frontal cortex of the guinea pig was measured by intracerebral dialysis. A constant infusion of sumatriptan (10(-8)-10(-7) M) dose-dependently reduced extracellular levels of 5-HT (e.g. 80 +/- 2% decrease from control levels of 5-HT at 10(-7) M). Peripheral administration of sumatriptan (50 micrograms/kg i.p. and 500 micrograms/kg i.p.) had no effect on extracellular levels of 5-HT in the frontal cortex. These data suggest that sumatriptan, when infused into the brain, inhibits the release of 5-HT by stimulating 5-HT autoreceptors and that the putative acute anti-migraine effects of sumatriptan are likely to be mediated by peripheral mechanisms.
Sleight
A J
AJ
Department of Neurology, Stanford University Medical Center, California 94305.
Cervenka
A
A
Peroutka
S J
SJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004563:Electrochemistry; D006168:Guinea Pigs; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D018170:Sumatriptan; D013997:Time Factors
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D012701:Serotonin; D018170:Sumatriptan