Ethyl (3<i>S</i>,4a<i>R</i>,6<i>S</i>,8a<i>R</i>)-6-(4-Ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso- quinoline-3-carboxylic Ester: A Prodrug of a GluR5 Kainate Receptor Antagonist Active in Two Animal Models of Acute Migraine

Abstract

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.