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Hans and List: The following abstract raises questions about the interpretation of longitudinal studies with Dopamine Transporter (DAT) binding and SPECT. They point out that the drugs downregulate the DAT binding in SHORT TERM experiments. They even emphasize that it is unknown whether this downregulation may be part of the therapeutic (or toxic) effects of these drugs. With short term downregulation of binding complicating the interpretation of the results, it is not even clear how much of the apparent decay detected in the "neuroprotection" studies was true decay or drug related downregulation - and whether such drug related downregulation may be a manifestation of a desired or undesired effect of either drug, not accelerated cell loss. With so many unknowns and questions, Dr. Lieberman's response "time will tell," makes the most sense. In the meantime, the claim that Mirapex slows down the disease is not justified. Jorge Romero TI - Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology 2001 Jun 12;56(11):1559-64 Guttman M, Stewart D, Hussey D, Wilson A, Houle S, Kish S Centre for Addiction and Mental Health, Division of Neurology, Department of Psychiatry, University of Toronto, Ontario, Canada. [log in to unmask] BACKGROUND: Animal data indicate that chronic exposure to dopaminergic drugs can alter levels of the dopamine transporter (DAT), which is critically involved in regulation of synaptic dopamine levels. DAT changes could influence the response to therapy in PD. METHODS: A randomized, assessor-blinded, placebo-controlled clinical trial was performed in subjects with early PD to determine whether L-dopa or pramipexole might regulate striatal DAT binding as measured by PET with [(11)C]RTI-32. Thirty clinically asymmetrical patients were randomly assigned to receive 6 weeks of L-dopa (300/75 mg/d), pramipexole (1.5 mg/d), or placebo; PET studies were performed before and after treatment. RESULTS: Mean interval change in DAT binding was significantly reduced by 16% to 22% in all striatal regions (caudate, anterior and posterior putamen) of the L-dopa-treated patients, whereas significant changes in the pramipexole-treated patients were limited to the contralateral caudate (-1! 5%), ipsilateral anterior putamen (-14%), and posterior putamen (-20%). In the placebo group there were significant changes in contralateral caudate (-11%) and ipsilateral anterior putamen (-12%). L-dopa and pramipexole produced similar clinical benefit. CONCLUSIONS: Short-term therapy with L-dopa and, to a lesser extent, pramipexole can modestly down-regulate striatal DAT in patients with early PD. Decreased striatal DAT could increase dopaminergic neurotransmission with potential benefit, but might also play a role in the development of dopamine-related response fluctuations in patients with advanced disease. Our data also suggest caution in interpretation of longitudinal imaging studies employing DAT to assess disease progression and the efficacy of neuroprotective agents. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn