Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids

Author: Hall, A.C.; Turcotte, C.M.; Betts, B.A.; Yeung, W.-Y.; Agyeman, A.S.; Burk, L.A.

Description: Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine EC20 responses increased by 496+/-113% and 135+/-56%, respectively). (+)-Menthol, 100 microM, reduced EC50 values for GABA and glycine from 82.8+/-9.9 to 25.0+/-1.8 microM, and from 98.7+/-8.6 to 75.7+/-9.4 microM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels.

Subject headings: Animals; Dose-Response Relationship, Drug; Drug Synergism; Female; Gene Expression; Glycine/pharmacology; Humans; Membrane Potentials/drug effects; Menthol/chemistry/pharmacology; Monoterpenes/pharmacology; Oocytes/drug effects/physiology; Patch-Clamp Techniques; Receptors, GABA-A/genetics/physiology; Receptors, Glycine/genetics/physiology; Stereoisomerism; Xenopus; gamma-Aminobutyric Acid/pharmacology

Publication year: 2004

Journal or book title: European Journal of Pharmacology

Volume: 506

Issue: 1

Pages: 9-16

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Type: Journal Article

Serial number: 505