Epilepsy is one of the most common neurological disorders. Even though antiepileptic drugs can afford a reasonably satisfactory treatment for 80% of diagnosed patients, chronic intractable epilepsy still affects a significant number of people and more effective and less harmful antiepileptic drugs are needed. Previous studies have shown that gamma-decanolactone has dose-dependent sedative effects, including hypnotic, anticonvulsant and hypothermic properties in mice. The present study reports an inhibitory effect of gamma-decanolactone on glutamate binding (96.8% with 5 mM) in rat cortex membranes. The non competitive nature of glutamate binding inhibition as a neurochemical correlate of the anticonvulsant activity of gamma-decanolactone may be a relevant mode of action for further drug development.