Kynurenate and 2-amino-5-phosphonovalerate alter the spinal seizures evoked by sudden cooling of toad isolated cords.

Sudden cooling of the isolated spinal cord of toads results in characteristic seizure-like activity in the hindlegs. In the present investigation, kynurenate (KYN), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and 2-amino-5-phosphonovalerate (APV), a competitive NMDA receptor antagonist, were tested in the pattern, latency and duration of the spinal seizures. APV, 1.3-2.5 mmol/kg and KYN, 2.6 mmol/kg, inhibited the tonic phase of the spinal seizures and prolonged the duration of the clonic phase after intralymphatic (i.l.) administration. The same effect was observed after intrathecal injection of either 10 or 20 mumol/20 microliter of each drug. The clonic phase was markedly attenuated by KYN at high doses of 5.3 or 10.6 mmol/kg, i.l., suggesting that non-NMDA receptors may have some mediation in the generation of that phase. Both antagonists retarded the onset of seizures indicating that activation of NMDA receptors is likely involved in the beginning of this convulsive-like activity. This model may be a useful technique to assay other excitatory amino acid antagonists.