Open AccessIsovaleric, Methylmalonic, and Propionic Acid Decrease Anesthetic EC50 in Tadpoles, Modulate Glycine Receptor Function, and Interact with the Lipid 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine
Author(s) -
Yun Weng,
Tienyi T. Hsu,
Jing Zhao,
Stefanie Y. Nishimura,
Gerald G. Fuller,
James M. Sonner
Publication year - 2009
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0b013e31819cd964
Subject(s) - anesthetic , isoflurane , gabaa receptor , glycine receptor , xenopus , glycine , receptor , medicine , amino acid , biophysics , pharmacology , biochemistry , chemistry , anesthesia , biology , gene
Elevated concentrations of isovaleric (IVA), methylmalonic (MMA), and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses. First, that these metabolites would have anesthetic-sparing effects, possibly being anesthetics by themselves. Second, that these compounds would modulate glycine and gamma-aminobutyric acid (GABA(A)) receptor function, increasing chloride currents through these channels as potent clinical inhaled anesthetics do. Third, that these compounds would affect physical properties of lipids.