ABSTRACT
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.
Subject(s)
Central Nervous System Stimulants/administration & dosage , Extracellular Fluid/drug effects , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Methylphenidate/administration & dosage , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapy , Positron-Emission Tomography , Putamen/drug effects , Administration, Oral , Adult , Aged , Basal Ganglia/diagnostic imaging , Basal Ganglia/drug effects , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/drug effects , Dopamine/metabolism , Dopamine D2 Receptor Antagonists , Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors , Female , Humans , Male , Middle Aged , Putamen/diagnostic imaging , Raclopride/pharmacokinetics , Treatment FailureABSTRACT
Several studies have shown that minocycline, a semisynthetic, second-generation tetracycline derivative, is neuroprotective in animal models of central nervous system trauma and several neurodegenerative diseases. Common to all these reports are the beneficial effects of minocycline in reducing neural inflammation and preventing cell death. Here, the authors review the proposed mechanisms of action of minocycline and suggest that minocycline may inhibit several aspects of the inflammatory response and prevent cell death through the inhibition of the p38 mitogen-activated protein kinase pathway, an important regulator of immune cell function and cell death.
