Effects of linalool on [H-3] MK801 and [H-3] muscimol binding in mouse cortical membranes

Linalool is a monoterpene compound reported to be a major component of esse ntial oils of several aromatic species. Several linalool-producing species are used in traditional medical systems for sedative purposes, including th e interruption and prevention of seizures. Previous studies in mice reveale d that linalool modulates glutamatergic (competitive antagonism Of L-[H-3]g lutamate binding, delayed intraperitoneal NMDA-induced convulsions and bloc kade of intracerebroventricular Quin-induced convulsions) and GABAergie tra nsmission (protection against pentylenetetrazol and picrotoxin-induced conv ulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [H-3]MK801 (NMDA antagonist) and [H-3]muscimol (GABAA agonist) to mouse cortical membranes. Linalool sho wed a dose dependent non-competitive inhibition of [H-3]MK801 binding (IC50 = 2.97 mM) but no effect on [H-3]muscimol binding. The data suggest that t he anticonvulsant mode of action of linalool includes a direct interaction with the NMDA receptor complex. The data do not, however, support a direct interaction of linalool with GABAA receptors, although changes in GABA-medi ated neuronal inhibition or effects on GABA release and uptake cannot be ru led out.