P-2 PURINOCEPTOR BLOCKER SURAMIN ANTAGONIZES NMDA RECEPTORS AND PROTECTS AGAINST EXCITATORY BEHAVIOR CAUSED BY NMDA RECEPTOR AGONIST (RS)-(TETRAZOL-5-YL)-GLYCINE IN RATS

It has been reported that suramin, an anthelminthic, trypanocidal agen t and an inhibitor of Pt receptors, may antagonise N-methyl-D-aspartat e (NMDA) subtype of the excitatory amino acid receptors. Both NMDA rec eptors and P-2X subclass Of P-2, receptors are ligand-gated Ca2+-selec tive channels and, since the increased influx of Ca2+ into neurons has been linked to neurotoxicity, simultaneous inhibition of P-2X and NMD A receptors in vivo by suramin could represent an effective neuroprote ctive treatment. We have found that suramin inhibited the binding of [ H-3]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 [H-3]kainate binding in vitro. In vivo, intracere broventricular (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. (C) 1997 Wiley-Liss, Inc.