Dopamine-derived tetrahydroisoquinolines. Novel inhibitors of dihydropteridine reductase.
Dopamine-derived tetrahydroisoquinolines, such as 3',4'-deoxynorlaudanosolinecarboxylic acid, higenamine-1-carboxylic acid, higenamine, and salsolinol, inhibit human liver dihydropteridine reductase noncompetitively with Ki values ranging from 1.5 to 90 microM. The enzyme is also inhibited noncompetitively by dopamine (Ki = 6 microM) and aminopterin (Ki = 100 microM) but uncompetitively by phenylpyruvic acid (Ki = 6.5 mM). These alkaloids may alter monoamine metabolism in mammals by inhibiting dihydropteridine reductase.
D000470:Alkaloids / Q000494:pharmacology; D004093:Dihydropteridine Reductase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D012490:Salsoline Alkaloids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines; D013765:Tetrahydropapaveroline / Q000031:analogs & derivatives / Q000494:pharmacology
C018501:3',4'-deoxynorlaudanosolinecarboxylic acid; D000470:Alkaloids; D007546:Isoquinolines; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; D013765:Tetrahydropapaveroline; C034773:higenamine-1-carboxylic acid; D004093:Dihydropteridine Reductase; D009247:NADH, NADPH Oxidoreductases; C012348:higenamine