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- W1994080662 abstract "γ-Aminobutyric acid type A (GABAA) receptors are the major mediators of fast synaptic inhibition in the central nervous system and thus play a crucial role in controlling the excitability of the brain. Diverse types of these ligand-gated chloride ion channels are a target for several therapeutically relevant drugs, such as benzodiazepines, barbiturates, neurosteroids and various general anaesthetics. However, these drugs interact in a non-selective way with several GABAA receptor subtypes and hence cause side effects such as reduced coordination, cognitive impairment, increased accident proneness, and development of dependence and abuse liability [1, 2]. In a search for new natural product derived scaffolds for GABAA receptor modulators we screened a plant extract library for GABAA receptor activity by means of a two-microelectrode voltage clamp assay using Xenopus laevis oocytes, which transiently express the target receptors of desired subunit composition. With the aid of an HPLC-based activity profiling approach [3], an active dichloromethane extract of Asarum heterotropoides herb (Aristolochiaceae) was fractionated in a time-based manner and submitted to the assay. In a next step, some of the compounds of the active time-based fractions were isolated and identified by on-line high-resolution mass spectrometry and off-line microprobe 1D and 2D NMR spectroscopy, using only milligram amounts. Dose-response experiments were carried out with these compounds in order to determine EC50 values and maximum potentiation of GABA-induced chloride influx, with the aid of the oocyte functional assay." @default.
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- W1994080662 date "2010-08-24" @default.
- W1994080662 modified "2023-09-26" @default.
- W1994080662 title "Identification of γ-aminobutyric acid type A (GABAA) receptor modulators: HPLC-based activity profiling of Asarum heterotropoides" @default.
- W1994080662 doi "https://doi.org/10.1055/s-0030-1264920" @default.
- W1994080662 hasPublicationYear "2010" @default.
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