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.
MeSH terms
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Acute Disease
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Administration, Oral
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Animals
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Biological Availability
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Calcium / metabolism
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Carboxylic Acids / chemical synthesis*
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology
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Cell Line
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Esters / chemical synthesis*
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Esters / chemistry
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Esters / pharmacology
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Excitatory Amino Acid Antagonists / chemical synthesis*
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Excitatory Amino Acid Antagonists / chemistry
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Excitatory Amino Acid Antagonists / pharmacology
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Humans
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Migraine Disorders / drug therapy*
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Kainic Acid / antagonists & inhibitors*
Substances
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6-(4-carboxyimidazol-1-ylmethyl)decahydroisoquinoline-3-carboxylic acid
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Carboxylic Acids
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Esters
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Excitatory Amino Acid Antagonists
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Gluk1 kainate receptor
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Isoquinolines
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Prodrugs
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Receptors, Kainic Acid
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ethyl 6-(4-ethoxycarbonylimidazol-1-ylmethyl)decahydroisoquinoline-3-carboxylic ester
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Calcium