Is Levodopa Toxic?
Stanley Fahn, MD
Columbia University
New York, NY

References:
Sulzer D, Bogulavsky J, Larsen KE, et al. Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci USA. 2000;97:11869-11874.

Peter Lansbury, PhD, Harvard Medical School.

Walton-Hadlock JL, Fahn S, Keiburtz K, Tanner CM, the Parkinson Study Group. Levodopa and the Progression of Parkinson's Disease. N Engl J Med. 2004;351:2498-2508.

Levodopa: How Does it Cause Motor Complications?
Jose A. Obeso, MD, PhD
Consultant and Professor of Neurology
Clinica Universitaria and Medical School
University of Navarra and FIMA
Pamplona, Spain

References:
Rodriguez Diaz M, Abdala P, Barroso-Chinea P, Obeso J, Gonzalez-Hernandez T. Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease. Behav Brain Res. 2001;122:79-92.

de la Fuente-Fernandez R, Lu JQ, Sossi V, et al. Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover. Ann Neurol. 2001;49:298-303.

de la Fuente-Fernandez R, Sossi V, Huang Z, et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. Brain. 2004;127:2747-2754.

Miller DW, Abercrombie ED. Role of high-affinity dopamine uptake and impulse activity in the appearance of extracellular dopamine in striatum after administration of exogenous L-DOPA: studies in intact and 6-hydroxydopamine-treated rats. J Neurochem. 1999;72:1516-1522.

Quinn N, Parkes JD, Marsden CD. Control of on/off phenomenon by continuous intravenous infusion of levodopa. Neurology. 1984;34:1131-1136.

Rodriguez M, Lera G, Vaamonde J, Luquin MR, Obeso JA. Motor response to apomorphine and levodopa in asymmetric Parkinson's disease. J Neurol Neurosurg Psychiatry. 1994;57:562-566.

 

Vaamonde J, Luquin MR, Obeso JA. Dopaminergic responsiveness to apomorphine after chronic treatment with subcutaneous lisuride infusion in Parkinson's disease. Mov Disord. 1990;5:260-262.

Calabresi P, Mercuri NB, Sancesario G, Bernardi G. Electrophysiology of dopamine-denervated striatal neurons. Implications for Parkinson's disease. Brain. 1993;116:433-452.

Picconi B, Centonze D, Rossi S, Bernardi G, Calabresi P. Therapeutic doses of L-dopa reverse hypersensitivity of corticostriatal D2-dopamine receports and gluatamatergic overactivity in experimental parkinsonism. Brain. 2004;127:1661-1669.

Calon F, Rajput AH, Hornykiewicz O, Bedard PJ, Di Paolo T. Levodopa-induced morot complications are associated with alterations of glutamate receports in Parkinson's disease. Neurobiol Dis. 2003;14:404-416.

Picconi B, Centonze D, Hakansson K, et al. Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia. Nat Neurosci. 2003;6:501-506.

Calon F, Morissette M, Rajput AH, Hornykiewicz O, Bedard PJ, Di Paolo T. Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications. Mov Discord. 2003;18:241-253.

Aubert I, Guigoni C, Hakansson K, et al. Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann Neurol. 2005;57:17-26.

Grandas F, Gancher S, Lera G, Rodriguez M, Woodward WR, Nutt J, Obeso JA. Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. Neurology. 1992;42:1287-1290.

Zamarbide, Rodriguez-Oroz, Alonso, Obeso. 2005.

 

A Rationale for the Early Use of Levodopa/Carbidopa/Entacapone
Fabrizio Stocci
IRCCS Neutomed
Rome, Italy

References:
Djaldetti R, Rosmarin V, Ziv I, Melamed E. The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease. Clin Neuropharmacol. 2001;24:95-98.

Mouradian MM, Juncos JL, Fabbrini G, Chase TN. Motor fluctuations in Parkinson's disease: pathogenetic and therapeutic studies. Ann Neurol. 1987;22:475-479.

Nutt JG, Fellman JH. Pharmacokinetics of levodopa. Clin Neuropharmacol. 1984;7:35-49.

Stocchi F, Ruggieri S, Vacca L, Olanow CW. Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease. Brain. 2002;125:2058-2066.

Stocchi F, Vacca L, De Pandis MF, Barbato L, Valente M, Ruggieri S. Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results. Neurol Sci. 2001;22:93-94.

Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005;62:905-910.

De la Fuente-Fernandez R, Lu JQ, Sossi V, et al. Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover. Ann Neurol. 2001;49:298-303.

Smith LA, Jackson MJ, Al-Barghouthy G, Rose S, Kuoppamaki M, Olanow W, Jenner P. Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naïve primates. Mov Disord. 2005;20:306-314.