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  • Title: Experimental hyperglycinaemia--an evaluation of the efficacy of strychnine therapy in nonketotic hyperglycinaemia.
    Author: von Wendt L.
    Journal: J Ment Defic Res; 1979 Sep; 23(3):195-205. PubMed ID: 513121.
    Abstract:
    A hyperglycinaemic state resembling the human disease nonketotic hyperglycinaemia (NKH) was created in male adult albino rabbits by injecting subcutaneously a ten percent aqueous glycine solution. A single dose of 300 mg./kg. caused a transient rise of plasma glycine level, but CSF glycine concentration began to rise only after an injection of 1,000 mg./kg. glycine. Repetition of the latter dose every four hours for twenty-four hours caused a gradual rise of both plasma and CSF glycine. Progressive neurological symptoms, highly resembling the early stages of NKH, developed during this prolonged loading. Numerous therapeutic approaches have been made to NKH which, if not fatal during the neonatal period, leads to severe psychomotor retardation, but only strychnine treatment (100--200 micrograms./kg/. day) has resulted in some improvement of the clinical condition of these patients. However, even the highest tolerated dose of strychnine (1 mg./kg./day) did not significantly alter the progression of neurological symptoms during glycine loading in the present study. All but one of twenty-nine rabbits succumbed during glycine loading, and only three of twenty-one survived when the glucine-antagonist strychnine was administered during glycine loading. Therefore, it seems probable that the protective effect of strychnine in a hyperglycinaemic state is of limited value. Glycine loading influenced intermediate amino acid metabolism in several ways, plasma alpha-amino-N and ammonia level rose and moderate metabolic acidosis developed during the last phase of the experiment. Profound alterations of levels of amino acids involved in glycine metabolism occurred in both blood plasma and cerebropinal fluid.
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