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Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD.
Neurology. 2001 Jun 12; 56(11):1559-64.Neur

Abstract

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 (-15%), 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.

Authors+Show Affiliations

Centre for Addiction and Mental Health, Division of Neurology, Department of Psychiatry, University of Toronto, Ontario, Canada. mguttman@idirect.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11402115

Citation

Guttman, M, et al. "Influence of L-dopa and Pramipexole On Striatal Dopamine Transporter in Early PD." Neurology, vol. 56, no. 11, 2001, pp. 1559-64.
Guttman M, Stewart D, Hussey D, et al. Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology. 2001;56(11):1559-64.
Guttman, M., Stewart, D., Hussey, D., Wilson, A., Houle, S., & Kish, S. (2001). Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology, 56(11), 1559-64.
Guttman M, et al. Influence of L-dopa and Pramipexole On Striatal Dopamine Transporter in Early PD. Neurology. 2001 Jun 12;56(11):1559-64. PubMed PMID: 11402115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. AU - Guttman,M, AU - Stewart,D, AU - Hussey,D, AU - Wilson,A, AU - Houle,S, AU - Kish,S, PY - 2001/6/13/pubmed PY - 2001/7/13/medline PY - 2001/6/13/entrez SP - 1559 EP - 64 JF - Neurology JO - Neurology VL - 56 IS - 11 N2 - 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 (-15%), 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. SN - 0028-3878 UR - https://www.unboundmedicine.com/medline/citation/11402115/Influence_of_L_dopa_and_pramipexole_on_striatal_dopamine_transporter_in_early_PD_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=11402115 DB - PRIME DP - Unbound Medicine ER -