One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia (TD), for which there is no satisfactory treatment. We have recently proposed that some cases of TD are associated with neuronal dysfunction resulting from excess free radical production occurring during catecholamine metabolism. We therefore decided to assess the efficacy of a powerful free radical scavenging agent, α-tocopherol (vitamin E), on the clinical signs of TD. We treated 15 patients with persistent TD with α-tocopherol and matched placebo in a randomized crossover design. Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale (AIMS) after treatment with α-tocopherol, but not after placebo. The mean reduction in the AIMS score with α-tocopherol was 43 percent, with seven patients showing a greater than 50 percent reduction in their dyskinesia. There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale, but no change was observed in scores on the Simpson-Angus Scale for Extrapyramidal Side Effects. Our findings are consistent with the possibility that α-tocopherol is beneficial in the treatment of some patients with TD, but further research is necessary to establish the efficacy of this agent.
Abstract N ‐acetyl‐ l ‐glutamine, pyroglutamic acid, and the butyl ester of pyroglutamic acid were isolated in pure form from an aqueous extract of human brain. These compounds were isolated by combination of paper and ion exchange chromatography. The isolated substance identified as N ‐acetyl‐ l ‐glutamine did not react with the ninhydrin reagent but yielded glutamic acid and ammonia upon acid hydrolysis. An acetyl hydrazide was identified by paper chromatography from hydrazinolysates of the isolated substance. The glutamic acid liberated by hydrolysis had the l ‐configuration. The results of elementary analysis of the isolated compound were in full accord with the analysis calculated for synthetic N ‐acetyl‐ l ‐glutamine. A large amount of pyroglutamic acid and a substance identical with the butyl ester of pyroglutamic acid were isolated in pure form. The results of our studies suggest that pyroglutamic and the butyl ester derivative were artifacts formed during the isolation and purification procedures.
Abstract— A substance identical with N ‐acetyl‐ l ‐alanine was isolated from an aqueous extract of human brain by a combination of paper and ion‐exchange Chromatography. The isolated substance did not react with ninhydrin reagent but yielded alanine upon acid hydrolysis. An acetyl hydrazide was identified by paper chromatography of hydrazinolysates of the isolated substance and N ‐acetyl‐ l ‐alanine. The unknown alanine had the l ‐configuration. The results of elementary analysis of the isolated compound were in full accord with the analysis calculated for synthetic N ‐acetyl‐ l ‐alanine.
SUMMARY A substance apparently identical with N ‐acetyl‐ l ‐glutamic acid was isolated from an aqueous extract from human brain by a combination of paper and ion exchange chromatography. The isolated substance does not react with ninhydrin reagent but yields glutamic acid upon acid hydrolysis. Acetyl hydrazide was identified by paper chromatography of hydrazinolysates of the isolated substance and N ‐acetyl‐ l ‐glutamic acid. The configuration was determined with l ‐specific hog kidney acylase.
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