Dopamine-derived tetrahydroisoquinolines. Novel inhibitors of dihydropteridine reductase.

Abstract

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.