Species of Searsia are used in traditional medicine to treat epilepsy. Previous studies on S. dentata and S. pyroides have shown that this is likely mediated via the N-methyl-d-aspartic acid (NMDA) receptor. Ethanolic extracts of leaves of six Searsia species were tested in a binding assay for affinity to the NMDA-receptor. S. dentata, S. gerrardii, S. glauca, S. natalensis, S. pentheri and S. pyroides all contained compounds with affinity to the NMDA-receptor. The species with the best affinity was S. pentheri. This might make it possible to use the Searsia species interchangeably, so the more accessible Searsia species can be used in traditional medicine.