Biochemical and pathological study of endogenous 1-benzyl-1,2,3,4-tetrahydroisoquinoline-induced parkinsonism in the mouse

Abe, Kenji; Taguchi, Kyoji; Wasai, Tomoko; Ren, Jin; Utsunomiya, Iku; Shinohara, Takayuki; Miyatake, Tadashi; Sano, Takehiro

doi:10.1016/s0006-8993(01)02573-2

Cited by 33 publications

(16 citation statements)

References 18 publications

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“…Figure 6 demonstrates that 1-BnTIQ, which is an analog of TIQ inducing the behavioral abnormality (Kotake et al 1995(Kotake et al , 1996, also does not induce the cell death. In the case of 1-BnTIQ, recently Abe et al (2001a) did not ®nd the loss of TH-positive cells, which is consistent with no alteration in the in vivo binding of [ 11 C]CFT to DATs in the present study.…”

Section: Discussionsupporting

confidence: 92%

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Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum

Ishiwata

Koyanagi

Abe

et al. 2001

Journal of Neurochemistry

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Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D 2 receptors (D2R) in the striatum. A signi®cant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent.

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Section: Discussionsupporting

confidence: 92%

“…1995, 1996), also does not induce the cell death. In the case of 1‐BnTIQ, recently Abe et al . (2001a) did not find the loss of TH‐positive cells, which is consistent with no alteration in the in vivo binding of [ 11 C]CFT to DATs in the present study.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum

Ishiwata

Koyanagi

Abe

et al. 2001

Journal of Neurochemistry

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“…Using a gas chromatography/mass spectrometry method, Yamakawa et al (1999) observed relatively high levels of 1BnTIQ in the substantia nigra compared to other brain regions of normal monkeys. Acute 1BnTIQ administration induced parkinsonism in both rodents and monkeys (Kotake et al 1996;Abe et al 2001). Our earlier study demonstrated that all the investigated tetrahydroisoquinolines had antidopaminergic properties, and we had suggested that differences in the neurotoxicity of various compounds of that group resulted from their diverse actions on dopamine catabolism.…”

Section: Introductionmentioning

confidence: 93%

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

2009

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1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is known to cause a parkinsonism-like syndrome in rodents and primates. In this study we evaluated the effects of single and multiple 1BnTIQ (50 mg/kg i.p.) administration on the concentrations of dopamine, serotonin, and respective metabolites (homovanillic acid, HVA; 3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and 5-hydroxyindolacetic acid, 5-HIAA), in substantia nigra, striatum (STR), and nucleus accumbens of Wistar rats. In addition, the effect of 1BnTIQ on locomotor activity and dopamine release in vivo was also estimated in rat STR. In a behavioral study, acute administration of 1BnTIQ (50 mg/kg i.p.) produced a significant decrease in exploratory locomotor activity. A high-performance liquid chromatography with electrochemical detection ex vivo study showed that a single injection of 1BnTIQ produced a dramatic fall in the dopamine concentration in the noted brain regions (approximately 65%; P < 0.01), but not in striatal serotonin. Moreover, 1BnTIQ reduced the content of the extraneuronal dopamine metabolite 3-MT by 70% (P < 0.01). Conversely, levels of DOPAC, HVA, and 5-HIAA were elevated by 220, 320, and 185%, respectively (P < 0.01). Interestingly, multiple 1BnTIQ treatments (50 mg/kg/day i.p. x 10 days) resulted in development of tolerance to its dopamine depressing effect, while the impairment of dopamine synthesis was persisted. An in vivo microdialysis study demonstrated that 1BnTIQ (50 mg/kg i.p.) produced a profound and long-lasting decrease in extraneuronal striatal dopamine. Concurrently, however, DOPAC and HVA were elevated. This comparison between ex vivo and in vivo effects of 1BnTIQ provides greater insight into the neurotoxic actions of 1BnTIQ specific to dopamine neurons. 1BnTIQ neurotoxicity may be related to an impairment of dopamine storage, leading to a fall in intraneuronal dopamine and enhanced dopamine catabolism through a monoamine oxidize-dependent oxidative pathway that results in free radical production and ultimate cell death. Because 1BnTIQ is an endogenous compound, it may be one of the factors responsible for idiopathic Parkinson's disease.

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“…87) In addition, 1-benzyl-TIQ profoundly stimulated DA release, which resulted in the competitive inhibition of [ 11 C]raclopride and DA D 2 receptor binding, but not the induction of receptor degeneration. 88) Recently, we confirmed by microdialysis technique that systemic single administration of 1-benzyl-TIQ increased striatal DA content and spontaneous activity in a dose-dependent manner in rats (unpublished data).…”

Section: Neurotoxicity Of 1-benzyl-1234-tetra-hydroisoquinoline (1mentioning

confidence: 98%

Synthesis and Neurotoxicity of Tetrahydroisoquinoline Derivatives for Studying Parkinson's Disease

Abe

Saitoh

Horiguchi

et al. 2005

Biological & Pharmaceutical Bulletin

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Parkinson's disease involves the progressive degeneration of dopaminergic neurons in the substantia nigra. However, the etiology of the disease remains to be elucidated. Endogenous amines, such as 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives present in the mammalian brain, are known to participate in the pathogenesis of Parkinson's disease. These endogenous neurotoxins have been extensively studied because of their structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an agent widely used for generating animal models of Parkinson's disease-like symptoms. Investigations of the synthesis and pharmacological properties of TIQ derivatives are expected to contribute to the development of new therapeutic agents for treating Parkinson's disease. In the present study, we describe more efficient synthesis methods for TIQ derivatives via Pummerertype cyclization of the substrate N-acyl sulfoxide. Furthermore, the modified Pummerer reaction provided a convenient and efficient method for synthesizing various TIQs. TIQ and its derivative, 1-benzyl-TIQ, can induce parkinsonism in primates and rodents. On the other hand, one TIQ derivative, 1-methyl-TIQ, has been shown to prevent MPTP, TIQ, and 1-benzyl-TIQ induced behavioral abnormalities. Therefore, TIQ derivatives are considered to play an important role in both the onset and prevention of Parkinson's disease. In this article, we focus on the synthesis and pharmacological aspects of 1,2,3,4-tetrahydroisoquinoline derivatives in Parkinson's disease.

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Biochemical and pathological study of endogenous 1-benzyl-1,2,3,4-tetrahydroisoquinoline-induced parkinsonism in the mouse

Cited by 33 publications

References 18 publications

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

Synthesis and Neurotoxicity of Tetrahydroisoquinoline Derivatives for Studying Parkinson's Disease

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Biochemical and pathological study of endogenous 1-benzyl-1,2,3,4-tetrahydroisoquinoline-induced parkinsonism in the mouse

Cited by 33 publications

References 18 publications

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D2 receptors in the mouse striatum

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D2 receptors in the mouse striatum

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

Synthesis and Neurotoxicity of Tetrahydroisoquinoline Derivatives for Studying Parkinson's Disease

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Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism‐preventing effect of 1‐MeTIQ by in vivo measurement of pre‐synaptic dopamine transporters and post‐synaptic dopamine D₂ receptors in the mouse striatum