Pyrrolidone carboxylic acid in acute and chronic alcoholism. Preclinical and clinical studies.
2-Pyrrolidone-5-carboxylic acid (PCA) is a cyclic derivative of glutamic acid, physiologically present in mammalian tissues. We herein report preclinical pharmacology experiments showing that PCA releases GABA from the cerebral cortex of freely-moving guinea-pigs and displays anti-anxiety effects in a simple approach-avoidance conflict situation in the rat. In clinical pharmacology experiments, PCA significantly shortens the plasma half-life of ethanol during acute intoxication. In chronic alcoholics a treatment with PCA (2g/day per 30 days) significantly hastens the recovery to physiological values of plasma gamma-glutamyl transferase activity and of the urinary excretion of glucaric acid, which are considered suitable markers of the trend of the alcoholic disease. The evidence emerging from preclinical and clinical studies strongly suggests that, by combining central anxiolytic actions with the peripheral recovery of the antioxidant defense system in the liver, PCA should be further investigated as an interesting endogenous molecule possibly helpful in the therapy of alcoholism.
Pellegrini-Giampietro
D E
DE
Moroni
F
F
Pistelli
A
A
Palmerani
B
B
Zorn
A M
AM
Peruzzi
S
S
Caramelli
L
L
Botti
P
P
Valenza
T
T
Antonini
M
M
D000435:Alcoholic Intoxication / Q000097:blood / Q000503:physiopathology*; D000437:Alcoholism / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011760:Pyrrolidinones; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D011761:Pyrrolidonecarboxylic Acid