Chapter 34 - Dopamine replacement for Parkinson's disease: Clinical approaches and experimental underpinnings

Parkinson's disease (PD) is characterized by a set of motor symptoms that depend on nigrostriatal dopaminergic degeneration and respond well to pharmacological dopamine replacement using L-DOPA. However, replacing dopamine with either L-DOPA or dopamine receptor agonists leads to the appearance of motor and nonmotor complications within a few years. Strong emphasis is currently placed on developing strategies for continuous drug delivery that can reduce fluctuations in motor and nonmotor states associated with standard oral therapy. Here, we summarize both currently available treatments and those that are in an advanced phase of clinical development. We then review key experimental findings elucidating how different treatment approaches affect dopamine-dependent signaling and behavior. We moreover discuss the fundamentally important and still open question of how dopamine replacement is to be achieved in order to maximize therapeutic efficacy and minimize the risk of debilitating complications.