Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter

Storch, Alexander; Ott, Sascha; Hwang, Yu I; Ortmann, R.; Hein, Andreas; Frenzel, Stefan; Matsubara, Kazuo; Ohta, Shigeru; Wolf, Hans; Schwarz, Johannes

doi:10.1016/s0006-2952(01)00922-4

Cited by 95 publications

(85 citation statements)

References 57 publications

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“…THP, salsolinol, and other isoquinoline derivatives are structurally related to the selective dopaminergic neurotoxin and PD-inducing agent MPTP/MPP ϩ and have been suggested to play a role in dopaminergic cell death characterized by PD (McNaught et al, 1998;Storch et al, 2002). Indeed, THP and salsolinol, have been demonstrated to be selective dopaminergic neurotoxins (Goto et al, 1997;Storch et al, 2002). Salsolinol and THP are found in high concentrations in the urine of PD patients on L-dopa treatment (Sandler et al, 1973) and salsolinol is found in the cerebrospinal fluid of untreated PD patients …”

Section: Isoquinoline Formationmentioning

confidence: 99%

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

2007

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Section: Isoquinoline Formationmentioning

confidence: 99%

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

2007

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“…[45][46][47] In addition, organic metals including manganese and carbon disulfide (CS 2 ) cause the neurodegeneration of subthalamic neuronal cells and neurobehavioral problems. 48 However, it is suggested that these metals can be considered specific dopaminergic toxins.…”

Section: Methamphetamine and Other Derivativesmentioning

confidence: 99%

Animal models of Parkinson's disease and their applications

Park

Zhao²,

Lee

2016

JPRLS

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Abstract:Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs mainly due to the degeneration of dopaminergic neuronal cells in the substantia nigra. l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective known therapy for PD. However, chronic l-DOPA administration results in a loss of drug efficacy and irreversible adverse effects, including l-DOPA-induced dyskinesia, affective disorders, and cognitive function disorders. To study the motor and non-motor symptomatic dysfunctions in PD, neurotoxin and genetic animal models of PD have been widely applied. However, these animal models do not exhibit all of the pathophysiological symptoms of PD. Regardless, neurotoxin rat and mouse models of PD have been commonly used in the development of bioactive components from natural herbal medicines. Here, the main animal models of PD and their applications have been introduced in order to aid the development of therapeutic and adjuvant agents.

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“…19,54) Recently, Storch et al reported that 2[N]-methylated isoquinoline derivatives were selectively toxic to dopaminergic neurons via uptake by the DAT, and they may play a role in the pathogenesis of PD. 92) On the other hand, Okuda et al investigated the effects of various neuroprotective 1-methyl-TIQ derivatives on salsolinol induced cell death in vitro, and they reported hydroxymethylated 1-methyl-TIQ had more potential for treating PD. 93) We believe that more toxic or more neuroprotective TIQ derivatives will be found.…”

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

confidence: 99%

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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Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter

Cited by 95 publications

References 57 publications

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Animal models of Parkinson's disease and their applications

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

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Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter

Cited by 95 publications

References 57 publications

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Animal models of Parkinson&#39;s disease and their applications

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

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Product

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Animal models of Parkinson's disease and their applications