New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET - [(11)C]raclopride study.

Abstract

Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [(11)C]raclopride binding to striatal D(2) dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10-14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [(11)C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (-7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D(2) receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D(2) receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D(2) receptors may represent a reinforcing mechanism of drug efficacy.

• Authors: R M Moresco, M A Volonte, C Messa, C Gobbo, L Galli, A Carpinelli, G Rizzo, A Panzacchi, M Franceschi, F Fazio
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 109 Issue 10 Pg. 1265-74 (Oct 2002) ISSN: 0300-9564 [Print] Austria
• PMID: 12373560 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Dopamine Antagonists
• Radiopharmaceuticals
• Raclopride
• Amantadine

Topics

• Aged
• Amantadine (pharmacology)
• Antiparkinson Agents (pharmacology)
• Brain Chemistry (drug effects)
• Caudate Nucleus (diagnostic imaging, metabolism)
• Dopamine Antagonists
• Female
• Humans
• Image Processing, Computer-Assisted
• Male
• Middle Aged
• Neostriatum (drug effects, metabolism)
• Parkinson Disease (diagnostic imaging, metabolism)
• Putamen (diagnostic imaging, metabolism)
• Raclopride
• Radiopharmaceuticals
• Tomography, Emission-Computed