Biosynthesis of a parkinsonism-preventing substance, 1-methyl-1,2,3,4-tetrahydroisoquinoline, is inhibited by parkinsonism-inducing compounds in rat brain mitochondrial fraction.

Abstract

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous parkinsonism-preventing substance, is enzymatically synthesized from 2-phenylethylamine (PEA) and pyruvate. We investigated whether exogenous or endogenous parkinsonism-inducing compounds inhibit 1 MeTIQ biosynthesis in a crude enzyme fraction from rat brain. Several parkinsonism-inducing compounds, including tetrahydroisoquinoline derivatives, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1 -methyl-4-phenylpyridinium (MPP+), beta-carboline and haloperidol, inhibited 1MeTIQ biosynthesis. The IC50 value of MPP+ for this enzyme is about 10 microM, lower than that for inhibition of mitochondrial complex I. We propose that the parkinsonism-inducing action of these compounds is at least partly due to inhibition of 1MeTIQ biosynthesis.

• Authors: T Yamakawa, S Ohta
• Journal: Neuroscience letters (Neurosci Lett) Vol. 259 Issue 3 Pg. 157-60 (Jan 15 1999) ISSN: 0304-3940 [Print] Ireland
• PMID: 10025582 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Biogenic Amines
• Carbolines
• Isoquinolines
• Neurotoxins
• Tetrahydroisoquinolines
• 1-methyl-1,2,3,4-tetrahydroisoquinoline
• Harmine
• norharman
• Haloperidol
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (pharmacology)
• Animals
• Antipsychotic Agents (pharmacology)
• Biogenic Amines (metabolism)
• Carbolines
• Haloperidol (pharmacology)
• Harmine (analogs & derivatives, pharmacology)
• Isoquinolines (antagonists & inhibitors, metabolism)
• Male
• Mitochondria (enzymology)
• Neurotoxins (pharmacology)
• Parkinson Disease, Secondary (enzymology, etiology)
• Rats
• Rats, Sprague-Dawley
• Tetrahydroisoquinolines