Current PD treatment. Due to the predominant dopaminergic deficit, symptomatic PD therapy for motor symptoms is mainly focused on regenerating levels of dopamine in the brain. Neuroprotective or disease-modifying therapies aim to slow or block the loss of dopamine neurons. Thus far there is no proven neuroprotective treatment, though drugs such as monoamine oxidase (MAO)-B inhibitors, creatine and isradipine are currently under investigation (Xxxxx et al., 2010). To date, the most frequently administered drug for symptomatic treatment of PD is L-dopa. Following its introduction as an anti-parkinsonian agent in 1968 (Cotzias, 1968), L-3,4- dihydroxyphenylalanine (Levodopa or L-dopa) is now the most commonly used dopaminergic drug. Even though it is the most efficacious drug treatment known for PD, its benefits are quite short-lived and long-term administration can lead to sensitisation of the dopaminergic system, resulting in motor-response complications including involuntary movements known as levodopa-induced dyskinesias (LIDs) (Figure 1.2C). Whilst L-dopa provides a mainly phasic dopaminergic stimulation, other dopamine agonists used in treating PD (e.g. pramipexole, ropinirole, pergolide) provide a more tonic stimulation and present different affinities for different dopamine receptors (Xxxxxxx and Xxxxxxxxxx, 2013). Additionally, other neurotransmitter systems such as acetylcholine, serotonin and noradrenaline are also implicated in PD and might provide alternative avenues for therapeutic targets. Apart from the characteristic motor symptoms, PD cases are also characterised by additional non-motor symptoms which can be categorised into three groups: neuropsychiatric (including psychotic episodes, amnesia, anxiety, depression, fatigue), autonomic (including urinary incontinence and excessive sweating) and sensory (including pain and numbness). Since most non-motor symptoms are frequently found in conjunction with motor symptoms, most methods of treatment are anti-parkinsonian therapies. Analgesics might be used to treat pain and alpha-blockers might be used for dysautonomic symptoms whilst anti-anxiety agents might be used to treat neuropsychiatric symptoms. Overall, treatment for non-motor symptoms is also predominantly symptomatic and no neuroprotective treatments are yet available.
