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Summary:The in vivo neuroprotective effect and brain levels of cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), a competitive N-methyl-D-aspartate (N MDA) antagonist, were compared with its in vitro neu roprotective effects. The dose-response for in vitro neu roprotection against both NMDA toxicity and combined oxygen-glucose deprivation (OGD) was determined in murine neocortical cultures. Primary cultures of neocor tical cells from fetal mice were injured by exposure to 500 fLM NMDA for 10 min or to OGD for 45 min. The effect of CGS 19755 in both injury paradigms was assessed mor phologically and quantitated by determination of lactate dehydrogenase release. Near complete neuroprotection was found at high doses of CGS 19755. The EDso for protection against NMDA toxicity was 25.4 fLmM, and against OGD the EDso was 15.2 fLM. For the in vivo

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The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.