Arylamine spider toxins antagonize NMDA receptor-mediated synaptic transmission in rat hippocampal slices.

The effects of arylamine spider toxins on synaptic transmission in rat hippocampal slices were investigated. Two different responses were monitored: the AMPA receptor-mediated population spike recorded in control buffer (selectively antagonized by DNQX) and the NMDA receptor-mediated EPSP recorded in nominally magnesium-free buffer containing 20 μM DNQX (selectively antagonized by AP5, AP7, and dizocilpine (MK-801)). The synthetic arylamine spider toxins JSTX-3, argiotoxin-636, and argiotoxin-659 were 26 to 73 times more potent at antagonizing the NMDA receptor-mediated EPSP (IC50 values ranging from 12 to 24 μM) than the AMPA receptor-mediated population spike (IC50 values ranging from 612 to 878 μM). These results indicate that arylamine spider toxins are selective antagonists of NMDA receptors in the mammalian CNS.