Pharmacological consideration of the symptoms resistant to dopaminergic therapy

Pharmacological treatment of Parkinson's disease (PD) is being developed for different aspects and stages of the condition. Although levodopa is still the most effective agent for treating patients with PD and a marked to excellent initial response to oral levodopa replacement is one of the clinical hallmarks of idiopathic PD, after treatment for more than 5 years, many patients develop instability of their motor response. This consists of dose-related periods of improvement followed by the wearing off of clinical effects some 3-4 h after dosing. With progressing disease, symptoms resistant to dopaminergic therapy emerge, such as freezing, dementia and hypotension. Dopaminergic or non-dopaminergic treatments and trials using agents with novel mechanisms of action were reviewed with a focus on the pathomechanism on symptoms resistant to dopaminergic therapy.