Enzymatic oxidation of the dopaminergic neurotoxin, 1 ( R), 2( N)-Dimethyl-6,7-Dihydroxy- l,2,3,4-Tetrahydroisoquinoline, into 1,2( N)-Dimethyl-6,7-Dihydroxyisoquinolinium ion

Abstract

The dopamine-derived alkaloid, 1( R),2( N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl( R)salsolinol] was found to be oxidized enzymatically into the more cytotoxic species, 1,2( N)-dimethyl-6,7-dihydroxyisoquinolinium ion, using enzyme sample prepared from human brain cortex. The values of the Michaelis constant and of the maximum velocity were 912 μM and 1368 pmol/min/mg protein, respectively. The enzyme was not inhibited by inhibitors of monoamine oxidase, but was sensitive to semicarbazide. The oxidation is discussed in relation to the dopaminergic neurotoxicity of N-methyl-( R)salsolinol.