title: Effects of linalool on [(3)H]MK801 and [(3)H] muscimol binding in mouse cortical membranes.
abstract: Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool-producing species are used in traditional medical systems for sedative purposes, including the interruption and prevention of seizures. Previous studies in mice revealed that linalool modulates glutamatergic (competitive antagonism of L-[(3)H]glutamate binding, delayed intraperitoneal NMDA-induced convulsions and blockade of intracerebroventricular Quin-induced convulsions) and GABAergic transmission (protection against pentylenetetrazol and picrotoxin-induced convulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [(3)H]MK801 (NMDA antagonist) and [(3)H]muscimol (GABA(A) agonist) to mouse cortical membranes. Linalool showed a dose dependent non-competitive inhibition of [(3)H]MK801 binding (IC(50) = 2.97 mM) but no effect on [(3)H]muscimol binding. The data suggest that the 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 GABA(A) receptors, although changes in GABA-mediated neuronal inhibition or effects on GABA release and uptake cannot be ruled out.
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, 90041-970, Porto Alegre, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Brum
authors.forename: E
authors.initials: E
authors.lastname: Elisabetsky
authors.forename: D
authors.initials: D
authors.lastname: Souza
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics*; D018755:GABA Agonists / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D039821:Monoterpenes; D009118:Muscimol / Q000493:pharmacokinetics*; D010938:Plant Oils / Q000494:pharmacology; D010946:Plants, Medicinal; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D013729:Terpenes / Q000494:pharmacology*; D014316:Tritium
chemical_list: D000080462:Acyclic Monoterpenes; D000927:Anticonvulsants; D018755:GABA Agonists; D039821:Monoterpenes; D010938:Plant Oils; D016194:Receptors, N-Methyl-D-Aspartate; D013729:Terpenes; D014316:Tritium; D009118:Muscimol; D016291:Dizocilpine Maleate; C018584:linalool