Pellegrini-Giampietro D E, Moroni F, Pistelli A, Palmerani B, Zorn A M, Peruzzi S, Caramelli L, Botti P, Valenza T, Antonini M
Recenti Prog Med. 1989 Mar;80(3):160-4.
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.
2-吡咯烷酮-5-羧酸（PCA）是谷氨酸的环状衍生物，生理上存在于哺乳动物组织中。我们在此报告临床前药理学实验，结果表明PCA可从自由活动的豚鼠大脑皮层释放γ-氨基丁酸（GABA），并在大鼠简单的避暗冲突实验中显示出抗焦虑作用。在临床药理学实验中，PCA可显著缩短急性中毒时乙醇的血浆半衰期。在慢性酒精中毒患者中，给予PCA（每30天每天2克）治疗可显著加速血浆γ-谷氨酰转移酶活性和葡萄糖醛酸尿排泄恢复至生理值，这二者被认为是酒精性疾病发展趋势的合适标志物。临床前和临床研究得出的证据有力地表明，通过将中枢抗焦虑作用与肝脏抗氧化防御系统的外周恢复相结合，PCA作为一种可能有助于治疗酒精中毒的有趣内源性分子，应进一步开展研究。
