The Role of 3-O-Methyldopa in the Side Effects of L: -dopa.

The Role of 3-O-Methyldopa in the Side Effects of L: -dopa. Research Abstract Details 

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The Role of 3-O-Methyldopa in the Side Effects of L: -dopa. Abstract Text:

Eun-Sook Y Lee,Hongtao Chen,Jennifer King,Clivel Charlton,Eun-Sook Y Lee,Hongtao Chen,Jennifer King,Clivel Charlton,

Long-term treatment of L: -dopa for Parkinson's disease (PD) patients induces adverse effects, including dyskinesia, on-off and wearing-off symptoms. However, the cause of these side effects has not been established to date. In the present study, therefore, 3-O-methyldopa (3-OMD), which is a major metabolite of L: -dopa, was tested to determine whether it plays a role in the aforementioned adverse effects. The effects of 3-OMD on the dopaminergic nervous system in the brain were investigated, by examining behavioral, biochemical, and cellular changes in male Sprague-Dawley rats and catecholamine-producing PC12 neuronal cells. The results revealed that the intracerebroventricular (icv) injection of 1 mumol of 3-OMD impaired locomotor activities by decreasing movement time (MT), total distance (TD), and the number of movement (NM) by 70, 74 and 61%, respectively. The biochemical analysis results showed that a single administration of 1 mumole of 3-OMD decreased the dopamine turnover rate (DOPAC/DA) by 40.0% in the rat striatum. 3-OMD inhibited dopamine transporter and uptake in rat brain striatal membranes and PC12 cells. The subacute administration of 3-OMD (5 days, icv) also significantly impaired the locomotor activities and catecholamine levels. 3-OMD induced cytotoxic effects via oxidative stress and decreased mitochondrial membrane potential in PC12 cells, indicating that 3-OMD can damage neuronal cells. Furthermore, 3-OMD potentiated L: -dopa toxicity and these toxic effects induced by both 3-OMD and L: -dopa were blocked by vitamin E (alpha-tocopherol) in PC12 cells, indicating that 3-OMD may increase the toxic effects of L: -dopa to some extent by oxidative stress. Therefore, the present study reveals that 3-OMD accumulation from long-term L: -dopa treatment may be involved in the adverse effects of L: -dopa therapy. Moreover, L: -dopa treatment might accelerate the progression of PD, at least in part, by 3-OMD.

The Role of 3-O-Methyldopa in the Side Effects of L: -dopa. Publishing Authors By Initials

ES Lee,H Chen,J King,C Charlton,ES Lee,H Chen,J King,C Charlton,

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The Role of 3-O-Methyldopa in the Side Effects of L: -dopa. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Neurochemical research

VOLUME: 33

Page Numbers: 401-11

Journal Abbreviation: Neurochem. Res.

ISSN: 0364-3190

DAY: 24

MONTH: 08

YEAR: 2007

The Role of 3-O-Methyldopa in the Side Effects of L: -dopa. Information

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LANGUAGE: eng

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AFFILIATION: Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN, 37208, USA, elee@mmc.edu.

Country: United States

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MEDLINETA: Neurochem Res

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