Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.
In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.
Stocchi
F
F
IRCCS San Raffaele Pisana, Rome, Italy.
Vacca
L
L
Grassini
P
P
De Pandis
M F
MF
Battaglia
G
G
Cattaneo
C
C
Fariello
R G
RG
D000328:Adult; D000409:Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001596:Benzylamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004298:Dopamine / Q000097:blood; D015259:Dopamine Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010300:Parkinson Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D010865:Pilot Projects; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D001596:Benzylamines; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa; C092797:safinamide; D008995:Monoamine Oxidase; D000409:Alanine; D004298:Dopamine