Inhibitors of GABA metabolism: implications for Huntington's disease.
Stereotaxic injection of kainic acid into rat striatum produces neuronal degeneration and neurochemical alterations resembling Huntington's disease (HD). Since correction of the deficiency in gamma-aminobutyric acid (GABA) in HD may be of therapeutic value, the efficacy of drugs that inhibit the GABA-degrading enzyme (GABA-T) in elevating the levels of GABA has been examined in the animal model for HD. High doses of di-N-propylacetic acid only partially correct the GABA deficiency in the striatum, whereas low doses of gamma-acetylenic GABA, a specific irreversible inhibitor of GABA-T, completely restore the levels of GABA in striatum and substantia nigra.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000480:Alkynes / Q000494:pharmacology; D000614:Aminocaproates / Q000494:pharmacology*; D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000201:enzymology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D051381:Rats; D013378:Substantia Nigra / Q000201:enzymology; D000637:Transaminases / Q000037:antagonists & inhibitors*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000480:Alkynes; D000614:Aminocaproates; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000637:Transaminases; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid; D015119:Aminocaproic Acid