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.
