TY - JOUR
T1 - New perspectives on neurochemical effects of amantadine in the brain of Parkinsonian patients
T2 - A PET - [ 11C]raclopride study
AU - Moresco, R. M.
AU - Volonte, M. A.
AU - Messa, C.
AU - Gobbo, C.
AU - Galli, L.
AU - Carpinelli, A.
AU - Rizzo, G.
AU - Panzacchi, A.
AU - Franceschi, M.
AU - Fazio, F.
PY - 2002
Y1 - 2002
N2 - 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 [ 11C]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 (200mg/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 [ 11C-]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 neosynthesis of D 2 receptors may represent a reinforcing mechanism of drug efficacy.
AB - 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 [ 11C]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 (200mg/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 [ 11C-]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 neosynthesis of D 2 receptors may represent a reinforcing mechanism of drug efficacy.
KW - D dopamine receptor
KW - Emission tomography
KW - NMDA antagonist
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U2 - 10.1007/s00702-002-0694-7
DO - 10.1007/s00702-002-0694-7
M3 - Article
C2 - 12373560
AN - SCOPUS:0036390350
SN - 0375-9245
VL - 109
SP - 1265
EP - 1274
JO - Journal of Neuro-Visceral Relations
JF - Journal of Neuro-Visceral Relations
IS - 10
ER -