(+)- And (-)-borneol: efficacious positive modulators of GABA action at human recombinant alpha1beta2gamma2L GABA(A) receptors.

来自 dx.doi.org

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阅读量：

301

作者：

RE Granger，EL Campbell，GAR Johnston

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摘要：

(+)-Borneol is a bicyclic monoterpene used for analgesia and anaesthesia in traditional Chinese and Japanese medicine and is found in the essential oils of medicinal herbs, such as valerian. (+)-Borneol was found to have a highly efficacious positive modulating action at GABA receptors, as did its enantiomer ()-borneol. The effects of these bicyclic monoterpenes alone and with GABA were evaluated at recombinant human αβγ GABA receptors expressed in 248μM) and ()-borneol (EC 237μM) enhanced the action of low concentrations of GABA by more than 1000%. These enhancing effects were highly dependent on the relative concentrations of the borneol enantiomer and GABA, and were insensitive to flumazenil indicating that (+)- and ()-borneol were not acting at classical benzodiazepine sites. The maximal responses to GABA were enhanced 19% by (+)-borneol and reduced 21% by ()-borneol. The borneol analogues isoborneol, ()-bornyl acetate and camphor, produced less marked effects. At high concentrations (>1.5mM) (+)- and ()-borneol directly activated GABA receptors producing 89% and 84%, respectively, of the maximal GABA response indicative of a weak partial agonist action. Although of lower potency, the highly efficacious positive modulatory actions of (+)- and ()-borneol on GABA responses were at least equivalent to that of the anaesthetic etomidate and much greater than that of diazepam or 5α-pregnan-3α-ol-20-one. The relatively rigid cage structure of these bicyclic monoterpenes and their high efficacy may aid in a greater understanding of molecular aspects of positive modulation of the activation of GABA receptors.

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关键词：

GABA receptor Monoterpene Valeriana officinalisXenopus oocyte

DOI：

10.1016/j.bcp.2005.01.002

被引量：

274

年份：

2005