Cinnamamides from Piper capense with affinity to the benzodiazepine site on the GABAA receptor

Epilepsy is among the most prevalent of the serious neurological disorders, affecting from 0.5–1.0% of the world's population and the prevalence of epilepsy in developing countries is generally higher than in developed countries [1]. Recently, plants used in South African traditional medicine for treatment of epilepsy and convulsion were examined for their pharmacological properties in the search for new and better anti-epileptic drugs [2, 3, 4]. The root of Piper capense L.f. (Piperaceae) is used in traditional South African medicine. A bioassay guided fractionation of an ethanolic extract using VLC, HPLC-UV, GC-MS and 1H-NMR led to the isolation and identification of cinnamamides with affinity to the benzodiazepine site on the GABAA receptor in the [3H]flumazenil receptor binding assay. The isolated cinnamides piperine and 4,5 dihydropiperine binded to the receptor with IC50 values of 0.9 and 1.7±mM respectively. . References: 1. Sander and Shorvon (1996)J Neurol Neurosurg Psych 65:433–443. 2. Svenningsen et al. (2006)J Ethnopharmacol. 103: 276–280. 3. Stafford, et al. (2005)J Ethnopharmacol 100: 210–215. 4. Risa, et al. (2004)J Ethnopharmacol 93:177–182