Planta Med 2010; 76 - WSI_5
DOI: 10.1055/s-0030-1264209

Natural coumarins and furanocoumarins as positive gabaergic modulators

J Singhuber 1, I Baburin 2, M Zehl 1, S Hering 2, B Kopp 1
  • 1Department of Pharmacognosy, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
  • 2Department of Pharmacology and Toxicology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria

Coumarins and furanocoumarins are natural compounds commonly found in plants of the Apiaceae and Rutaceae family. Many of these plants are used as spasmolytic and sedative agents in traditional medicinal systems worldwide [1]. Thus, the effects of various (furano)coumarins on human recombinant α1β2γ2S GABAA receptors were investigated using the voltage-clamp technique according to [2]. From 18 substances tested (100µM), only 2 potentiated the GABA induced chloride current above + 100%. The present study suggests that prenyl residues are essential for the postitive modulatory activity of this substance class. Furthermore it can be concluded that coumarins are more potent than furanocoumarins and that geranyl side chains or other bulky residues diminish the observed effect in both groups. The most potent substances were osthole (7-methoxy-8-(3-methylbut-2-enyl)chromen-2-one) and oxypeucedanin (4-[[(2S)-3,3-dimethyloxiran-2-yl]methoxy]furo[3,2-g]chromen-7-one) with a mean potentiation (±s.e.) of 125% (±11%) and 110% (±12%), respectively.

Fig.1: Osthole and oxypeucedanin

Acknowledgements: This project was supported by the University of Vienna as part of the Initiativkolleg „Molecular Drug Targets“

References: 1. Murray et al. (1982). The natural coumarins: occurrence, chemistry and biochemistry. Wiley. London.

2. Baburin I. et al. (2006). Pflugers Arch. 453: 117–23.