Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer.
4-Hydroxytetrahydroisoquinoline (4OH-TIQ) was detected as a metabolite of a possible parkinsonism-inducing substance, tetrahydroisoquinoline (TIQ), in rat liver microsomes and rat urine. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson's disease.
Ohta
S
S
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Tachikawa
O
O
Makino
Y
Y
Tasaki
Y
Y
Hirobe
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D003647:Debrisoquin / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007546:Isoquinolines / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D008297:Male; D008862:Microsomes, Liver / Q000032:analysis; D010300:Parkinson Disease / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D003647:Debrisoquin