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The ursane triterpenoids, asiatic acid 1 and madecassic acid 2, are the major pharmacological constituents ofCentella asiatica, commonly known as Gotu Kola, which is used traditionally for the treatment of anxiety and for the improvement of cognition and memory. Using the two-electrode voltage-clamp technique, these triterpenes, and some semisynthetic derivatives, were found to exhibit selective negative modulation of different subtypes of the GABAA receptor expressed inXenopus laevisoocytes. Despite differing by only one hydroxyl group, asiatic acid 1 was found to be a negative modulator of the GABA-induced current atα1β2γ2L,α2β2γ2L andα5β3γ2L GABAA receptors, while madecassic acid 2 was not. Asiatic acid 1 exhibited the greatest effect atα1β2γ2L (IC50 37.05μm), followed byα5β3γ2L (IC50 64.05μm) thenα2β2γ2L (IC50 427.2μm) receptors. Conversion of the carboxylic acid group of asiatic acid 1 to a carboxamide group (2α,3β,23-trihydroxy-urs-12-en-28-amide 5) resulted in enhanced inhibition at both theα1β2γ2L (IC50 14.07μm) andα2β2γ2L receptor subtypes (IC50 28.41μm). The results of this study, and the involvement ofα5-containing GABAA receptors in cognition and memory, suggest that asiatic acid 1 may be a lead compound for the enhancement of cognition and memory.