Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.
In this study, we assessed the changes of endogenous dopamine (DA) levels in response to methylphenidate in 5 patients with idiopathic Parkinson's disease (PD) and 6 healthy controls. Three-dimensional positron emission tomography was performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1 hour following the administration of oral methylphenidate (0.8 mg/kg) to assess changes in dopamine levels indirectly. Oral methylphenidate produced no significant change in extracellular DA levels in the putamen, as estimated by comparing changes in RAC binding at baseline and 1 hour following its administration in PD subjects and healthy controls. However, there were small changes in RAC binding of opposite direction in caudate and ventral striatal regions compared between the two groups. Although there was no consistent improvement in motor function in the PD group, some patients did experience a subjective high in response to methylphenidate (MP). Failure of oral MP to alter extracellular DA levels in putamen could result from degeneration of presynaptic dopaminergic terminals, with consequent severe reductions in the levels of endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo neurochemical support for the lack of clinical efficacy following MP in PD patients and are also in keeping with reduced DA release following amphetamine in PD subjects.
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. kavehm@interchange.ubc.ca
Kaveh M
KM
Koochesfahani
Raúl
R
de la Fuente-Fernández
Vesna
V
Sossi
Michael
M
Schulzer
Lakshmi N
LN
Yatham
Thomas J
TJ
Ruth
Stephan
S
Blinder
A Jon
AJ
Stoessl
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D045604:Extracellular Fluid / Q000187:drug effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects*; D020891:Raclopride / Q000493:pharmacokinetics; D017211:Treatment Failure
D000697:Central Nervous System Stimulants; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine