A COMPARISON OF (-AND-F-10047 AND MK-801 ON CORTICAL SPREADING DEPRESSION()SK)

MK-801 and (+)SK&F 10047 produced a dose-related inhibition of the EEG suppression and cortical hyperemia associated with cortical spreading depression (CSD) and reduced the CSD propagation rate; ED(50) = 1 mg/ kg, i.v. and 15 mg/kg, i.v., respectively. MK-801 had a delayed onset of action (inversely related to dose) and a prolonged duration of acti on at all doses (> 2 h). In contrast, (+)SK&F 10047 had a rapid onset of action (< 30 min) and a predictable dose-related duration of action . These results suggests that an efficacious compound acting with mode rate affinity as a non-competitive antagonist at the NMDA-receptor cha nnel may possess a preferable time-course and toxicity profile when co mpared to agents acting similarly, but with high affinity.