Dopamine Reuptake Inhibitors in Parkinson’s Disease: A Review of Nonhuman Primate Studies and Clinical Trials

摘要: Striatal dopamine deficiency is the core feature of pathology Parkinson's disease (PD), and replacement with l-3,4-dihydroxyphenylalanine (l-DOPA) mainstay PD treatment. Unfortunately, chronic l-DOPA administration marred by emergence dyskinesia wearing-off. Alternatives to for alleviation parkinsonism are interest, although none can match efficacy date. Catechol-O-methyltransferase monoamine oxidase inhibitors currently used alleviate wearing-off, but they do not increase "on-time" without exacerbating dyskinesia. Alternate approaches in generally (and wearing-off dyskinesia, specifically) therefore urgently needed. Inasmuch as synaptic levels, transporter (DAT) inhibitors, whether selective or have actions on noradrenaline serotonin transporters, theoretically represent an attractive way per se potentially enhance antiparkinsonian action (provided that sufficient terminals remain within striatum). Several nonhuman primate studies clinical trials been performed evaluate potential DAT PD. In this article, we review trials, summarize current knowledge PD, propose a hypothesis how tailoring selectivity might maximize benefits inhibition