The role of NMDA-receptor type glutamatergic antagonists dextromethorphan or ketamine in the treatment of nonketotic hyperglycinemia: A critical reassessment.
Molecular genetics and metabolism November 1, 2024 Johan L K Van Hove 7 citations
Glycine was thought to overactivate NMDA-type glutamate receptors in nonketotic hyperglycinemia, leading to the use of antagonists like dextromethorphan or ketamine. However, the discovery that D-serine, another endogenous activator, is markedly decreased in this condition suggests the receptors may instead be underactivated, challenging the original hypothesis. No clear clinical evidence shows added therapeutic benefit from dextromethorphan or ketamine beyond glycine reduction strategies. The systematic use of these NMDA receptor antagonists in nonketotic hyperglycinemia should be reevaluated, especially given emerging potential adverse effects.