Effective therapy for Parkinson's disease (PD) has existed for over 45 years. Currently, levodopa, the precursor to dopamine, remains the most consistently effective symptomatic treatment. Pharmacological treatments, such as dopamine agonists and monoamine oxidase (MAO) inhibitors, augment and replace endogenous dopamine loss. 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 dopaminergic armamentarium: loss of effect and lack of effect. Dopaminergic medications often initially improve motor symptoms; however, as the disease progresses, patients develop motor complications. Initially, the duration of medication action shortens with the subsequent development of dyskinesia and on/off fluctuations that complicate dosing and can worsen quality of life. This is particularly problematic in younger patients. Certain aspects of PD do not respond well to dopaminergic drugs, such as sleep disturbances, cognition, mood, balance, freezing of gait, gastroenterological and urological symptoms, and bulbar symptoms, as these symptoms often result from nondopaminergic pathology. Finally, no available medication can definitely claim to offer anything other than symptomatic benefit.
New medications can be broadly classified into three categories: (i) improved versions of drugs that employ similar mechanisms of action as currently available medications, (ii) drugs with novel mechanisms of action, and (iii) drugs designed to treat only a particular aspect of the disease (psychosis, dementia, etc.). In this chapter, we will only discuss new drugs designed to treat the motor features of PD.
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