Differential Binding of Ergot Compounds to Human versus Rat 5-HT2 Cortical Receptors

Abstract
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.

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