Parkinson’s disease: will therapy move beyond dopaminergic medication?

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that affects more than 1% of individuals older than 60 years. The motor symptoms of Parkinson’s disease are accompanied by a multitude of nonmotor symptoms, which usually predominate in the later stages of the disease and influence patients’ quality of life. Complex, interconnected neuronal systems involving dopamine and other neurotransmitters participate in the development of the disease and are responsible for the motor and nonmotor symptoms. Effective symptomatic therapies are available, but long-term management and neuroprotection still remain controversial issues. Levodopa is the ‘gold standard’ of symptomatic therapy, but treatment of the nondopaminergic and nonmotor symptoms of Parkinson’s disease necessitates the targeting of transmitter systems beyond dopamine. Among these, 5-HT agonists, glutamate antagonists, adenosine A2 antagonists and the a-adrenergic-receptor antagonists are detailed. Among glutamate antagonists, the neuroactive kynurenines may exert a neuroprotective effect.