Tetrahydroisoquinoline lacks dopaminergic nigrostriatal neurotoxicity in mice.
1,2,3,4-Tetrahydroisoquinoline (TIQ) has been reported to occur in human brain, with its content being 10-fold higher in the brain of a patient with Parkinson's disease (PD) than in that of a control subject. This congener of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could be formed in brain by the condensation of phenylethylamine with metabolically formed formaldehyde. Phenylethylamine contents are greatly increased in the tissues of untreated patients with phenylketonuria. We injected C57 black mice repeatedly with maximal tolerated doses of TIQ, but later found no reduction in the contents of dopamine and its metabolites in their striata. We doubt that TIQ is a cause of PD, especially since the disorder has not been reported to occur in elderly patients with phenylketonuria.
Perry
T L
TL
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Jones
K
K
Hansen
S
S
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007546:Isoquinolines / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D004298:Dopamine