Effects of 3,4-dihydroxyphenylpyruvic acid and its triacetylated derivative on DOPA decarboxylase.
Various drugs have been studied in order to improve the bioavailability of L-DOPA. In the present study, the alpha-ketoacid of L-DOPA, 3,4-dihydroxyphenylpyruvic acid (DHPPA) and its fully acetylated derivative, triacetoxyphenylpyruvic acid (TAPPA), were investigated. These substances were shown to be equally strong DOPA decarboxylase inhibitors in vitro. The inhibitory activity was, however, only about 1/2000 of that of carbidopa and 1/10 of that of L-alpha-methyldopa. In vivo studies in the rat showed that when either DHPPA or TAPPA was given orally concomitantly with L-DOPA, only DHPPA, which is a transaminase inhibitor, enhanced the L-DOPA induced rise in the cerebral dopamine concentration. TAPPA had, however, an enhancing effect on the L-DOPA-induced rise in the serum L-DOPA concentration. The weak L-DOPA-sparing effect of TAPPA could be explained by its inhibitory effect on DOPA decarboxylase and the marked L-DOPA-sparing effect of DHPPA by its action on both transamination and decarboxylation.
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001921:Brain / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008297:Male; D010667:Phenylpyruvic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D010667:Phenylpyruvic Acids; C019344:3,4-dihydroxyphenylpyruvic acid; D007980:Levodopa; C036043:triacetoxyphenylpyruvic acid