ScopeGABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation.Methods and resultsSingle volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABAA receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As Sideritis extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABAA receptors, a high-throughput method was used for identification of the most effective terpenoid substances on GABA-affinity of α1β2γ2 receptors expressed in transfected cell lines. Isopulegol, pinocarveol, verbenol, and myrtenol were the most potent modifiers of GABAA receptor function.ConclusionComparing the chemical structures, the action of terpenes on GABAA receptors is most probably due to the presence of hydroxyl groups and a bicyclic character of the substances tested. We propose an allosteric modulation independent from the γ2 subunit and similar to the action of alcohols and anesthetics.

Sideritis spp. is a member of the Labiateae family, used in traditional folk medicine and as a calming tea preparation. Dichloromethane extracts of the aerial parts of four Sideritis species were prepared, and the volatile fractions were separated via solvent‐assisted flavour evaporation distillation. In vitro electrophysiological techniques were used to investigate the physiological effects of these aroma extracts on ionotropic γ‐aminobutyric acid receptors (GABAA) in comparison to extracts of Lavandula spp. (lavender) obtained by the same approach. The plant extracts of Sideritis spp. and Lavandula spp. increased the maximal current responses gated by the agonist GABA, both in whole cell patch clamp recordings as well as in two electrode voltage clamp assays. Thereby, the volatile fractions caused a dose‐dependent enhancement of GABAergic currents. Differences in activity between the various species were probably due to variations in odorant composition, either on a qualitative or quantitative basis. Thus, the plant material contains volatile organic compounds, which are able to modulate a GABA‐mediated response and thereby possibly contribute to a sedative effect in vivo. Copyright © 2012 John Wiley & Sons, Ltd.

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