A comparison of (+)SK&F 10047 and MK-801 on cortical spreading depression.
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; ED50 = 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 action 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 moderate affinity as a non-competitive antagonist at the NMDA-receptor channel may possess a preferable time-course and toxicity profile when compared to agents acting similarly, but with high affinity.
Willette
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RN
Division of Pharmacology, SmithKline-Beecham Pharmaceuticals, King of Prussia, PA 19406.
Lysko
P G
PG
Sauermelch
C F
CF
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D006940:Hyperemia / Q000139:chemically induced; D007275:Injections, Intravenous; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010620:Phenazocine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D016202:N-Methylaspartate; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine