P2 purinoceptor blocker suramin antagonises NMDA receptors and protects against excitatory behaviour caused by NMDA receptor agonist (RS)-(tetrazol-5-yl)-glycine in rats

It has been reported that suramin, an anthelminthic, trypanocidal agent and an inhibitor of P₂ receptors, may antagonise N-methyl-D-aspartate (NMDA) subtype of the excitatory amino acid receptors. Both NMDA receptors and P_2X subclass of P₂ receptors are ligand-gated Ca²⁺-selective channels and, since the increased influx of Ca²⁺ into neurons has been linked to neurotoxicity, simultaneous inhibition of P_2X and NMDA receptors in vivo by suramin could represent an effective neuroprotective treatment. We have found that suramin inhibited the binding of ³H]CGP 39653 to NMDA receptor binding sites in vitro and reduced the frequency of NMDA channel openings in patch-clamp studies. Suramin (1 mM) had no effect on ³H]kainate binding in vitro. In vivo, intracerebroventricular (ICV) injections of suramin (70 nmol/brain) antagonised convulsive effects of the NMDA agonist (RS)-(tetrazol-5-yl)-glycine (TZG, LY 285265). Suramin, however, did not prevent neurotoxic lesions in the hippocampus caused by ICV administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression. J. Neurosci. Res. 49:627–638, 1997. © 1997 Wiley-Liss, Inc.