کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001650 | 1118542 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
(+)- And (â)-borneol: efficacious positive modulators of GABA action at human recombinant α1β2γ2L GABAA receptors
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
(+)-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 GABAA receptors, as did its enantiomer (â)-borneol. The effects of these bicyclic monoterpenes alone and with GABA were evaluated at recombinant human α1β2γ2L GABAA receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. (+)-Borneol (EC50 248 μM) and (â)-borneol (EC50 237 μM) 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 (â)-borneol were not acting at classical benzodiazepine sites. The maximal responses to GABA were enhanced 19% by (+)-borneol and reduced 21% by (â)-borneol. The borneol analogues isoborneol, (â)-bornyl acetate and camphor, produced less marked effects. At high concentrations (>1.5 mM) (+)- and (â)-borneol directly activated GABAA 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 (â)-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 GABAA receptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 7, 1 April 2005, Pages 1101-1111
Journal: Biochemical Pharmacology - Volume 69, Issue 7, 1 April 2005, Pages 1101-1111
نویسندگان
Renee E. Granger, Erica L. Campbell, Graham A.R. Johnston,