TETRAHYDROPAPAVEROLINE AND ITS DERIVATIVES INHIBIT DOPAMINE UPTAKE THROUGH DOPAMINE TRANSPORTER EXPRESSED IN HEK293 CELLS

Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detec ted in brain and urine of Parkinsonian patients on L-dopa medication, and in the urine and brain of rats after L-dopa or acute ethanol admin istration. Since THP is considered to be synthesized from dopamine, it may affect dopaminergic neurons through the reuptake system, i.e. dop amine transporter (DAT). To determine whether THP has affinity for DAT , we generated a cell line which stably expresses DAT and examined whe ther THP and its derivatives could inhibit [H-3]DA uptake in these cel ls. Ki of THP and three derivatives (1-benzyl-l,2,3,4-tetrahydroisoqui noline (1BnTIQ), 4'-dibydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3 ',4' DHBnTIQ) and -dihydroxy-1-benzyl-1,2,3,4-tetrahydroisoquinoline ( 6,7 DHBnTIQ)) for inhibition of [H-3]DA uptake were about 41, 35, 23 a nd 93 mu M, respectively, which were similar to the Ki of 1-methyl-4-p henylpyridinium ion (MPP+) (28 mu M). These results suggest that THP a nd its derivatives might be uptaken through DAT and be involved in Par kinson's disease and/or alcohol addiction. (C) 1998 Elsevier Science I reland Ltd. All rights reserved.