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July 17, 2002

Brain Imaging to Assess the Effects of Dopamine Agonists on Progression of Parkinson Disease

Author Affiliations

Stephen J.LurieMD, PhD, Senior EditorIndividualAuthor

JAMA. 2002;288(3):311-313. doi:10.1001/jama.288.3.311

To the Editor: Dr Marek and colleagues1 reported that patients with Parkinson disease (PD) who were treated with pramipexole for 22 to 46 months had evidence of less dopamine neuron degeneration (as assessed by single-photon computed tomography [SPECT]) than did patients who were treated with levodopa for a similar period.

It is unclear whether these results simply reflect the pharmacological effects of pramipexole on dopamine transporter (DAT) expression, or the ability of DAT to sequester the radiologic marker 2β-carboxymethoxy-3β(4-iodophenyl)tropane (β-CIT). If pramipexole simply increased DAT expression in surviving nerve terminals, imaging could falsely indicate more surviving neurons. Pramipexole alteration of DAT function might have a similar influence. Drugs that bind to dopaminergic receptors have significant effects on DAT phosphorylation, functions, expression, and turnover.2 Dopamine agonists and levodopa can influence DAT synthesis and degradation, with D1- and D2-linked second messenger systems often affecting DAT expression in opposite ways.2 Dopamine generated from levodopa stimulates both classes of receptors, while pramipexole spares D1 receptors.3