Occurrence and distribution of salsolinol-like compound, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ) in parkinsonian brains

J Neural Transm (Vienna). 2012 Apr;119(4):435-41. doi: 10.1007/s00702-011-0724-4. Epub 2011 Nov 8.

Abstract

Parkinson's disease (PD) arises from the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is well known to cause Parkinsonism in humans with neurotoxicity specific for dopaminergic neurons. The experience with MPTP supports the hypothesis that endogenous or xenobiotic neurotoxins are involved in the pathogenesis of PD in humans. In our study, 1-acetyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydro-isoquinoline (ADTIQ), a novel compound, was found in frozen human brain tissues. The formation of ADTIQ was demonstrated using dopamine and methylglyoxal under physiological conditions. Methylglyoxal is a by-product of glycolysis. ADTIQ and its precursors, dopamine and methylglyoxal, were detected in different regions of frozen human brains such as the substantia nigra, caudate nucleus, putamen, frontal cortex, and the cerebellum. A significant difference in ADTIQ levels between control and Parkinson's patients was found; for instance, the ADTIQ level in putamen of PD patients was 0.76 ± 0.27 nmol/g compared to 0.10 ± 0.01 nmol/g in control. Our results might indicate that ADTIQ is possibly related to Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Brain / metabolism*
  • Brain / pathology
  • Chromatography, High Pressure Liquid
  • Dopamine / metabolism
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Parkinsonian Disorders / pathology*
  • Postmortem Changes
  • Pyruvaldehyde / metabolism
  • Tetrahydroisoquinolines / chemistry
  • Tetrahydroisoquinolines / metabolism*

Substances

  • 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
  • Tetrahydroisoquinolines
  • Pyruvaldehyde
  • Dopamine