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Pharmacological Properties of Levodopa

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Levodopa-Induced Dyskinesia in Parkinson's Disease

Abstract

Therapy with L-3,4-dihydroxyphenylalanine (levodopa, l-DOPA), the immediate precursor of dopamine, is the most effective treatment for Parkinson’s disease. However, despite its undeniable antiparkinsonian efficacy, l-DOPA administration does not recapitulate dopaminergic transmission as it occurs under physiological conditions, notably because of short plasma half-life and variable absorption. Hence, in the non-parkinsonian state, dopamine levels in the striatum are constantly maintained above a threshold and can further increase, in a stimulus-dependent manner. In contrast, in PD, dopamine levels are markedly reduced and transiently increased with each administration of l-DOPA, leading to variable levels of striatal dopamine, alternating between peaks and troughs. Such fluctuations in dopamine levels lead to discontinuous, pulsatile stimulation of dopamine receptors within the striatum, which is thought to be a key determinant underlying the dyskinetic state. Therapeutic approaches that would produce continuous drug delivery (CDD) and ensuing continuous dopaminergic stimulation (CDS) have been actively sought. After a brief historical review, this chapter summarizes the biochemical and pharmacokinetic properties of l-DOPA. Results of studies assessing the effect of CDD/CDS paradigms on dyskinesia development and on the severity of dyskinesia once it has developed are then presented.

Disclosures: None

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Acknowledgments

This work was supported by the Department of Pharmacology and Faculty of Medicine of Université de Montréal.

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Huot, P. (2014). Pharmacological Properties of Levodopa. In: Fox, S., Brotchie, J. (eds) Levodopa-Induced Dyskinesia in Parkinson's Disease. Springer, London. https://doi.org/10.1007/978-1-4471-6503-3_9

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