The non-competitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglasii) tubers

Water hemlocks (Cicuta spp.) are acutely toxic members of the Umbellierae family; the toxicity is due to the presence of C17-polyacetylenes such as cicutoxin. There is only limited evidence of noncompetitive antagonism by C17-polyacetylenes at GABAA receptors. In this work with WSS-1 cells, we documented the noncompetitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglasii) and modulated the actions of the extract with a pretreatment of 10 μM midazolam. [Display omitted] •A Cicuta douglasii extract depressed maximal GABA responses in WSS-1 cells, characteristic of non-competitive antagonism.•Pretreatment of WSS-1 cells with midazolam reversed the actions of the extract on the WSS-1 cell GABA response.•The actions of the extract were concentration-dependent.