Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline

K. Kikuchi, Y. Nagatsu, Y. Makino, Tadahiko Mashino, S. Ohta, M. Hirobe

Research output: Contribution to journalArticle

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Abstract

14C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76% of TIQ and 72% of 1MeTIQ were excreted unchanged, and 2.7 and 8.7% were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4%) and 2-methyl-1MeTIQ (0.7%) were detected. Isoquinoline (2.5%) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0%) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90% was unchanged TIQ or 1MeTIQ. These data indicate that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalDrug Metabolism and Disposition
Volume19
Issue number1
Publication statusPublished - 1991
Externally publishedYes

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Parkinsonian Disorders
Blood-Brain Barrier
Metabolism
Metabolites
Brain
1,2,3,4-tetrahydroisoquinoline
1-methyl-1,2,3,4-tetrahydroisoquinoline
Tissue Distribution
Hydroxyl Radical
Amines
Parkinson Disease
Rats
Blood
Tissue
Derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline. / Kikuchi, K.; Nagatsu, Y.; Makino, Y.; Mashino, Tadahiko; Ohta, S.; Hirobe, M.

In: Drug Metabolism and Disposition, Vol. 19, No. 1, 1991, p. 257-262.

Research output: Contribution to journalArticle

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abstract = "14C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76{\%} of TIQ and 72{\%} of 1MeTIQ were excreted unchanged, and 2.7 and 8.7{\%} were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4{\%}) and 2-methyl-1MeTIQ (0.7{\%}) were detected. Isoquinoline (2.5{\%}) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0{\%}) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90{\%} was unchanged TIQ or 1MeTIQ. These data indicate that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.",
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