TY - JOUR
T1 - Isoniazid-induced alteration of CSF neurotransmitter amino acids in Huntington's disease
AU - Manyam, Bala V.
AU - Ferraro, Thomas N.
AU - Hare, Theodore A.
N1 - Funding Information:
Supportedin part by the Medical ResearchP ro-gram of the VeteransA dministrationb, y NIH re-searchs upportG rantRR 5414,a nd by the Percival E. and Ethyl Brown FoererdeFro undation.
PY - 1987/4/7
Y1 - 1987/4/7
N2 - During a randomized, double-blind, crossover, placebo-controlled clinical trial of isoniazid (plus pyridoxine) in Huntington's disease (HD), amino acids and related amino compounds were measured in both cerebrospinal fluid (CSF) and plasma utilizing a newly developed high-performance liquid chromatography ion-exchange/fluorometric assay method. Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (± S.E.M.) levels of γ-aminobutyric acid, aspartate, homocarnosine, ornithine, histidine, α-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of β-alanine in both CSF and plasma. These alterations can be traced to inhibition of decarboxylation and transamination reactions requiring the cofactor pyridoxal phosphate and may be related to the observed equivocal clinical response in the HD patients. The differential influence of isoniazid on plasma and CSF amino acid profiles suggests that alterations of CNS amino acid metabolism may be reflected in CSF, and that isoniazid-induced alterations of amino acid metabolism in the CNS differ from those in the periphery.
AB - During a randomized, double-blind, crossover, placebo-controlled clinical trial of isoniazid (plus pyridoxine) in Huntington's disease (HD), amino acids and related amino compounds were measured in both cerebrospinal fluid (CSF) and plasma utilizing a newly developed high-performance liquid chromatography ion-exchange/fluorometric assay method. Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (± S.E.M.) levels of γ-aminobutyric acid, aspartate, homocarnosine, ornithine, histidine, α-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of β-alanine in both CSF and plasma. These alterations can be traced to inhibition of decarboxylation and transamination reactions requiring the cofactor pyridoxal phosphate and may be related to the observed equivocal clinical response in the HD patients. The differential influence of isoniazid on plasma and CSF amino acid profiles suggests that alterations of CNS amino acid metabolism may be reflected in CSF, and that isoniazid-induced alterations of amino acid metabolism in the CNS differ from those in the periphery.
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U2 - 10.1016/0006-8993(87)90364-7
DO - 10.1016/0006-8993(87)90364-7
M3 - Article
C2 - 2885064
AN - SCOPUS:0023229288
SN - 0006-8993
VL - 408
SP - 125
EP - 130
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -