title: Current status of NMDA antagonist interventions in the treatment of nonketotic hyperglycinemia.
abstract: Impairment of the catabolism of glycine caused by "failure" of the glycine cleavage enzyme complex results in an inability to oxidatively decarboxylate this amino acid. As a result of this inability, the alpha carbon of glycine does not enter the one-carbon pool, leading to its reduction or depletion, and toxic accumulation of this amino acid neurotransmitter occurs. Strategies for the treatment of the clinical condition known as nonketotic hyperglycinemia, an autosomal recessive disorder associated with absent or diminished glycine cleavage enzyme activity, include reduction of the glycine burden, replenishment of the one-carbon pool, and antagonism of the neurotransmitter effects of glycine. Until recently, antagonism focused on interference with the glycine-associated chloride ionophore that is enriched in the brain stem and spinal cord, using strychnine as a specific intervention. However, the recent recognition of a "strychnine-insensitive" binding site for glycine on the N-methyl-D-aspartic acid (NMDA) receptor complex, a glutamate-gated cationic channel, has led to some newer approaches. Also, the recognition of milder, atypical variants of classic nonketotic hyperglycinemia has stimulated efforts to evaluate the therapeutic efficacy of these strategies to antagonize the NMDA receptor complex.
authors.affiliation: Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, D.C. 20422, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: R B
authors.initials: RB
authors.lastname: Rosse
authors.forename: J
authors.initials: J
authors.lastname: Mastropaolo
mesh_terms: D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005998:Glycine / Q000097:blood*; D006801:Humans; D006944:Hyperglycemic Hyperosmolar Nonketotic Coma / Q000188:drug therapy; D007649:Ketamine / Q000627:therapeutic use; D008659:Metabolic Diseases / Q000097:blood / Q000188:drug therapy*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D014364:Tryptophan / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D007649:Ketamine; D014364:Tryptophan; D005998:Glycine