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Homocysteine-induced convulsions in the rat: Protection by homoserine, serine, betaine, glycine and glucose

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Abstract

Intraperitoneal injection into rats of 5.5 mM/kg ofdl-homocysteine (free base) ordl-homocysteine thiolactone · HCl resulted in violent convulsions (approx. 50%) and some fatalities (approx. 15%), following a short, initial period of depressant activity. Metabolically related metabolites (viz. methionine, serine, homoserine, cysteine and homocystine) showed no convulsant activity and virtually no lethal effects at doses as high as 7.4 mM/kg. At 7.4 mM/kg, homocysteine and its lactone resulted in 95% convulsions and 90% fatalities. These obervations point to a structural factor for convulsant activity indl-homocysteine not found in the related methionine metabolites tested. The half-maximal convulsant dose (CD50) was 750 (698–806) mg/kg and the half-maximal lethal dose (LD50) was 840 (794–889) mg/kg, both values having Litchfield-Wilcoxon confidence limits of 19/20. Prior intraperitineal injection of large doses (14.8 mM/kg) of homoserine, serine, betaine, glycine and glucose protected against convulsions and death induced by the CD50 dose (i.e. 750 mg/kg) ofdl-homocysteine. Our findings indicate that, of all the major metabolites of methionine tested, homocysteine would seem to be the only one which is epileptogenic and the most toxic (to the point of lethality).

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Authors and Affiliations

  1. U.S. Veterans Administration Hospital, 19320, Coatesville, Pennsylvania, USA

    Herbert Sprince Chief of Research Biochemistry, Clarence M. Parker & Joseph A. Josephs Jr.

  2. The Departments of Psychiatry and Pharmacology, Jefferson Medical College and Medical Center, 19107, Philadelphia, Pennsylvania, USA

    Herbert Sprince Chief of Research Biochemistry, Clarence M. Parker & Joseph A. Josephs Jr.

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  1. Herbert Sprince Chief of Research Biochemistry
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  2. Clarence M. Parker
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  3. Joseph A. Josephs Jr.
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Sprince, H., Parker, C.M. & Josephs, J.A. Homocysteine-induced convulsions in the rat: Protection by homoserine, serine, betaine, glycine and glucose. Agents and Actions 1, 9–13 (1969). https://doi.org/10.1007/BF01990014

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  • DOI: https://doi.org/10.1007/BF01990014

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