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 P2X 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 P2X 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 (I.C.V.) 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 I.C.V. administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression.
Ong
W Y
WY
Department of Anatomy, National University of Singapore, Singapore.
Motin
L G
LG
Hansen
M A
MA
Dias
L S
LS
Ayrout
C
C
Bennett
M R
MR
Balcar
V J
VJ
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D010875:Pipecolic Acids / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D058919:Purinergic P2 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014344:Trypanocidal Agents; C053672:selfotel; D013498:Suramin; D005998:Glycine