ChemMedChem

Cover image for Vol. 12 Issue 21

Editorial Board Chairs: Karl-Heinz Altmann, Antonello Mai, Rainer Metternich. Editor: David Peralta

Impact Factor: 3.225

ISI Journal Citation Reports © Ranking: 2016: 17/60 (Chemistry Medicinal); 73/257 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

March 18, 2010

VIP: Highly Potent Modulation of GABAA Receptors by Valerenic Acid Derivatives

VIP: Highly Potent Modulation of GABAA Receptors by Valerenic Acid DerivativesSascha Kopp, Roland Baur, Erwin Sigel, Hanns Möhler, and Karl-Heinz Altmann*

γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter, and many of its effects are mediated by the GABAA receptor subtype. Current benzodiazepine GABAA receptor modulators are mostly nonselective. Focusing their attention on the natural product valerenic acid, which was recently shown to be an allosteric modulator at GABAA receptors, Altmann and colleagues report the first systematic SAR study for the interaction of valerenic acid derivatives with the GABAA receptor. They identified a number of derivatives that produce a significantly higher potentiation of the effect of GABA at GABAA receptors than the natural product itself, including a tetrazole derivative that is at least one order of magnitude more potent than valerenic acid. This compound is a good example of how the biological activity of a natural product can indeed be significantly improved by chemical optimization.

Received February 12, 2010; published online March 16, 2010, DOI: 10.1002/cmdc.201000062.

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