l-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP+ and β-carbolinium: a microdialysis study in rats

Matsubara, Kazuo; Senda, Tomoko; Uezono, Takumi; Awaya, Toshio; Ogawa, Satoshi; Chiba, Kaoru; Shimizu, Keiko; Hayase, Nobumasa; Kimura, Kojiro

doi:10.1016/s0304-3940(01)01601-9

Cited by 37 publications

(16 citation statements)

References 17 publications

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“…It has become apparent in recent years that selegiline pretreatment can protect many neurons from a variety of neurotoxins damaging dopaminergic, adrenergic, serotoninergic, and cholinergic neurons (Table I; Magyar and Haberle, 1999;Matsubara et al, 2001) …”

Section: Selegiline Protects Against Mptp-mentioning

confidence: 99%

Neuroprotective actions of selegiline

Ebadi

Sharma

Shaik

et al. 2002

J of Neuroscience Research

123

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Selegiline, a selective inhibitor of monoamine oxidase-B (MAO-B), was one of the first adjunct therapies in clinical neurology. A retrospective analysis of data from patients with Parkinson's disease found a significant increase in survival in those treated with selegiline plus L-dopa compared with L-dopa alone. The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory action. Pretreatment with selegiline can protect neurons against a variety of neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 6-hydroxydopamine, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), methyl-␤-acetoxyethyl-2-chloroethylamine (AF64A), and 5,6-dihydroxyserotonin, which damage dopaminergic, adrenergic, cholinergic, and sertoninergic neurons, respectively. Selegiline produces an amphetamine-like effect, enhances the release of dopamine, and blocks the reuptake of dopamine. It stimulates gene expression of L-aromatic amino acid decarboxylase, increases striatal phenylethylamine levels, and activates dopamine receptors. Selegiline reduces the production of oxidative radicals, up-regulates superoxide dismutase and catalase, and suppresses nonenzymatic and iron-catalyzed autooxidation of dopamine. Selegiline compensates for loss of target-derived trophic support, delays apoptosis in serum-deprived cells, and blocks apoptosis-related fall in the mitochondrial membrane potential. Most of the aforementioned properties occur independently of selegiline's efficacy to inhibit MAO-B. © 2002 Wiley-Liss, Inc.Selegiline (deprenyl; Jumex), a noncompetitive monoamine oxidase-B (MAO-B) inhibitor, has continued to hold a fascination for clinicians and researchers since it was first synthesized as a "psychic energizer." The "neuroprotective effects" of selegiline became evident when it was found that it blocked the parkinsonism-inducing effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; see Langston and Tanner, 2000).MPTP as a neurotoxin has attracted the attention of many investigators owing to its capacity in humans and nonhuman primates to induce neuropathologic abnormalities (rigidity, resting tremor, akinesia, etc.) similar to those observed in patients with idiopathic Parkinson's disease (PD). As in PD also after administration of MPTP, the observed symptoms are caused by depletion of dopamine in the neostriatum following selective degeneration of the dopaminergic neurons of the substantia nigra pars compacta (SNpc).MPTP's capacity to induce PD was discovered accidentally when several drug addicts in California developed numerous symptoms of PD after self-administration of a "synthetic heroin" containing MPTP as a contaminant byproduct. Numerous investigations have since been carried out in which MPTP was administered in vivo to primates and rodents as well as in vitro using cell cultures. Today, MPTP-induced toxicity represents one of the most interesting models for investigating the pathogenesis of the parkinsonian syndrome. However, its mechanism of action is stil...

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Section: Selegiline Protects Against Mptp-mentioning

confidence: 99%

Neuroprotective actions of selegiline

Ebadi

Sharma

Shaik

et al. 2002

J of Neuroscience Research

123

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“…The above effects are also inherent in other dopamine toxicants exhibiting structural similarity to MPTP, which are found among pyridine, isoquinoline, and b-carboline derivatives [31,47,69,78]. The neurotoxicity of their metabolites is also related to the release of mitochondrial energy at a result of the inhibition of MPTP complexes [23,36].…”

Section: -Methyl-4-phenyl-1236-tetrahydropyridine and Related Commentioning

confidence: 99%

“…An example is offered by 2,9-Me 2 NH + cation (XXXVI) representing a toxic form of norharman [69,78]. It was established that neurotoxicity is manifested only if both N-methyl groups are present in the structure [69].…”

Section: -Methyl-4-phenyl-1236-tetrahydropyridine and Related Commentioning

confidence: 99%

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Neurotoxins and Drugs for the Treatment of Parkinson's Disease. Part I: Neurotoxins, Levodopa, and Agents Influencing Dopamine Metabolism (A Review)

2005

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“…It was reported that antioxidant properties are inherent in some antiparkinsonian drugs such as apomorphine [13], selegiline [14], and ergoline derivatives [15].…”

Section: Antioxidantsmentioning

confidence: 99%

Neurotoxins and medicinals for the treatment of Parkinson’s disease. Part 3: Drugs indirectly influencing the dopaminergic system (a review)

2005

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In recent years, much attention has been given to antiparkinsonian drugs which do not directly influence dopamine and its receptors but nevertheless produce a positive therapeutic action. This part of the review summarizes recent findings and discusses hypotheses concerning the role of antioxidants and inhibitors of adenosine and glutamate NMDA receptors in the treatment of Parkinson's disease. Promising approaches are provided by operative methods and gene therapy. The development of Parkinson's disease genetics will probably provide a key to the next generation of antiparkinsonian drugs.

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l-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP+ and β-carbolinium: a microdialysis study in rats

Cited by 37 publications

References 17 publications

Neuroprotective actions of selegiline

Neuroprotective actions of selegiline

Neurotoxins and Drugs for the Treatment of Parkinson's Disease. Part I: Neurotoxins, Levodopa, and Agents Influencing Dopamine Metabolism (A Review)

Neurotoxins and medicinals for the treatment of Parkinson’s disease. Part 3: Drugs indirectly influencing the dopaminergic system (a review)

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