5-benzyloxytryptamine: a relatively selective 5-hydroxytryptamine 1D/1B agent.
The ability of nineteen tryptamine derivatives to interact with putative 5-hydroxytryptamine1D (5-HT1D) receptor binding sites in bovine caudate was analyzed. Sixteen of the nineteen agents competed, with variable potency, for these binding sites with Hill slopes of approximately unity. By contrast, 5-carboxyamidotryptamine (5-CT), sumatriptan and 5-benzyloxytryptamine (5-BT) competed with Hill slope values significantly less than unity. These three drugs share, in comparison to the sixteen other tryptamines, relatively large substitutions at the 5-position of the indole moiety. Additional radioligand binding studies with 5-BT indicate that the drug shows relative selectivity for 5-HT1D/1B binding sites. Functionally, 5-BT and sumatriptan inhibit 3H-5-HT release from guinea pig cortical synaptosomes with equal potency but 5-BT is significantly less efficacious than sumatriptan. These data indicate that 5-BT is a relatively selective partial agonist at 5-HT1D receptors.
Peroutka
S J
SJ
Department of Neurology, Stanford University School of Medicine, CA 94305.
McCarthy
B G
BG
Guan
X M
XM
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D013574:Synaptosomes / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C070179:5-benzyloxytryptamine; D012701:Serotonin; D018170:Sumatriptan