Investigational Pharmacological Treatments for Parkinson’s Disease

Effective therapy for Parkinson’s disease (PD) has existed for 40 years. Currently, levodopa, the precursor to dopamine, remains the most consistently effective medication. Most other pharmacologic treatments, such as dopamine agonists, augment and replace the endogenous dopamine loss that causes PD symptoms. Other treatments such as anticholinergic medications and amantadine often help symptoms through nondopaminergic mechanisms. Numerous other medications such as antidepressants and antipsychotics are used to treat specific symptoms in PD. Conceptually, there are two major shortcomings to our current pharmacological armamentarium: loss of effect and lack of effect. Dopaminergic medications often initially improve symptoms, but as the disease progresses, patients develop motor fluctuations. Initially, the duration of medication action shortens. The subsequent development of dyskinesia and on/off phenomenon complicates dosing and markedly worsens quality of life. This is particularly problematic in younger patients. Certain aspects of PD never respond well to dopaminergic drugs, such as cognition, mood, balance, gait freezing, gastroenterological and urological symptoms, and bulbar symptoms. Finally, no available medication can