Differential binding of ergot compounds to human versus rat 5-HT2 cortical receptors.
Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.
Hagen
J D
JD
Department of Neurology, Stanford University School of Medicine, Calif.
Pierce
P A
PA
Peroutka
S J
SJ
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D004876:Ergot Alkaloids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity
D004876:Ergot Alkaloids; D011985:Receptors, Serotonin; D007650:Ketanserin