a once-daily comt inhibitor. dopamine agonists dopamine agonists that bind to dopamine receptors in the brain have similar effects to levodopa. these were initially used as a complementary therapy to levodopa for individuals experiencing levodopa complications (on-off fluctuations and dyskinesias); they are mainly used on their own as first therapy for the motor symptoms of pd with the aim of delaying the initiation of levodopa therapy, thus delaying the onset of levodopa's complications. dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine, and lisuride. though dopamine agonists are less effective than levodopa at controlling pd motor symptoms, they are effective enough to manage these symptoms in the first years of treatment. dyskinesias due to dopamine agonists are rare in younger people who have pd, but along with other complications, become more common with older age at onset. thus, dopamine agonists are the preferred initial treatment for younger-onset pd, and levodopa is preferred for older-onset pd. dopamine agonists produce side effects, including drowsiness, hallucinations, insomnia, nausea, and constipation. side effects appear with minimal clinically effective doses giving the physician reason to search for a different drug. agonists have been related to impulse-control disorders (such as increased sexual activity, eating, gambling, and shopping) more strongly than other antiparkinson medications. they tend to be more expensive than levodopa. apomorphine, a dopamine agonist, may be used to reduce off periods and dyskinesia in late pd. it is administered only by intermittent injections or continuous subcutaneous infusions. secondary effects such as confusion and hallucinations are common, individuals receiving apomorphine treatment should be closely monitored. two dopamine agonists administered through skin patches (lisuride and rotigotine) are useful for people in the initial stages and possibly to control off states in those in advanced states. due to an increased risk of cardiac fibrosis with ergot-derived dopamine agonists (bromocriptine, cabergoline, dihydroergocryptine, lisuride, and pergolide), they should only be considered for adjunct therapy to levodopa. mao-b inhibitors mao-b inhibitors (safinamide, selegiline and rasagiline) increase the amount of dopamine in the basal ganglia by inhibiting the activity of monoamine oxidase b, an enzyme that breaks down dopamine. they have been found to help alleviate motor symptoms when used as monotherapy (on their own); when used in conjunction with levodopa, time spent in the off phase is reduced.: 1924 selegiline has been shown to delay the need for beginning levodopa, suggesting that it might be neuroprotective and slow the progression of the disease. an initial study indicated that selegiline in combination with levodopa increased the risk of death, but this has been refuted. common side effects are nausea, dizziness, insomnia, sleepiness, and (in selegiline and rasagiline) orthostatic hypotension. mao-bs are known to increase serotonin and cause a potentially dangerous condition known as serotonin syndrome. other drugs other drugs such as amantadine may be useful as treatment of motor symptoms, but evidence for use is lacking. anticholinergics should not be used for dyskinesia or motor fluctuations but may be considered topically for drooling. a diverse range of symptoms beyond those related to motor function can be treated pharmaceutically. examples are the use of quetiapine or clozapine for psychosis, cholinesterase inhibitors or memantine for dementia, and modafinil for excessive daytime sleepiness. in 2016, pimavanserin was approved for the management of pd psychosis. doxepin and rasagline may reduce physical fatigue in pd. surgery placement of an electrode into the brain: the head is stabilised in a frame for stereotactic surgery. treating motor symptoms with surgery was once a common practice but the discovery of levodopa has decreased the amount of procedures. studies have led to great improvements in surgical techniques, so surgery can be used in people with advanced pd for who drug therapy is no longer sufficient. surgery for pd can be divided in two main groups – lesional and deep brain stimulation (dbs). target areas for dbs or lesions include the thalamus, globus pallidus, or subthalamic nucleus. dbs involves the implantation of a medical device called a neurostimulator, which sends electrical impulses to specific parts of the brain. dbs is recommended for people who have pd with motor fluctuations and tremor inadequately controlled by medication, or to those who are intolerant to medication lacking severe neuropsychiatric problems. other less common surgical therapies involve intentional formation of lesions to suppress overactivity of specific subcortical areas. for example, pallidotomy involves surgical destruction of the globus pallidus to control dyskinesia. four areas of the brain have been treated with neural stimulators in pd. these are the globus pallidus interna, thalamus, subthalamic nucleus, and pedunculopontine nucleus. dbs of the globus pallidus interna improves motor function, while dbs of the thalamic dbs improves tremor, but has little impact on bradykinesia or rigidity. dbs of the subthalamic nucleus is usually avoided if a history of depression or neurocognitive impairment is present. dbs of the subthalamic nucleus is associated with a reduction in medication. pedunculopontine nucleus dbs remains experimental at present. generally, dbs is associated with 30–60% improvement in motor score evaluations. rehabilitation further information: management of parkinson's disease exercise programs are recommended in people with pd. some evidence shows that speech or mobility problems can improve with rehabilitation, although studies are scarce and of low quality. regular physical exercise with or without physical therapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life. when an exercise program is performed under the supervision of a physiotherapist, more improvements occur in motor symptoms, mental and emotional functions, daily living activities, and quality of life compared with a self-supervised exercise program at home. clinical exercises may be an effective intervention targeting overall well-being of individuals with parkinson's. improvement in motor function and depression may happen. in improving flexibility and range of motion for people experiencing rigidity, generalized relaxation techniques such as gentle rocking have been found to decrease excessive muscle tension. other effective techniques to promote relaxation include slow rotational movements of the extremities and trunk, rhythmic initiation, diaphragmatic breathing, and meditation techniques. as for gait and addressing the challenges associated with the disease such as hypokinesia, shuffling, and decreased arm swing, physiotherapists have a variety of strategies to improve functional mobility and safety. areas of interest concerning gait during rehabilitation programs focus on improving gait speed, the base of support, stride length, and trunk and arm-swing movement. strategies include using assistive equipment (pole walking and treadmill walking), verbal cueing (manual, visual, and auditory), exercises (marching and pnf patterns), and altering environments (surfaces, inputs, open vs. closed). strengthening exercises have shown improvements in strength and motor function for people with primary muscular weakness and weakness related to inactivity with mild to moderate pd, but reports show an interaction between strength and the time the medications were taken. therefore, people with pd should perform exercises 45 minutes to one hour after medications when they are capable. deep diaphragmatic breathing exercises are beneficial in improving chest-wall mobility and vital capacity decreased by a forward flexed posture and respiratory dysfunctions in advanced pd. exercise may improve constipation. if exercise reduces physical fatigue in pd remains unclear. strength training exercise has been shown to increase manual dexterity in pd patients after exercising with manual putty. this positively affects everyday life when gripping for pd patients. the lee silverman voice treatment (lsvt) is one of the most widely practiced treatments for speech disorders associated with pd. speech therapy and specifically lsvt may improve speech. occupational therapy (ot) aims to promote health and quality of life by helping people with the disease to participate in a large percentage of their daily living activities. few studies have been conducted on the effectiveness of ot, and their quality is poor, although with some indication that it may improve motor skills and quality of life for the duration of the therapy. palliative care the goal of palliative care is to improve quality of life for both the patient and family by providing relief from the symptoms and stress of illnesses. as parkinson's is uncurable, treatments focus on slowing decline and improving quality of life and are therefore palliative. palliative care should be involved earlier, rather than later, in the disease course. palliative care specialists can help with physical symptoms, emotional factors such as loss of function and jobs, depression, fear, and existential concerns. along with offering emotional support to both the affected person and family, palliative care addresses goals of care. people with pd may have difficult decisions to make as the disease progresses, such as wishes for feeding tube, noninvasive ventilator or tracheostomy, wishes for or against cardiopulmonary resuscitation, and when to use hospice care. palliative-care team members can help answer questions and guide people with pd on these complex and emotional topics to help them make decisions based on values. muscles and nerves that control the digestive process may be affected by pd, resulting in constipation and gastroparesis (prolonged emptying of stomach contents). a balanced diet, based on periodical nutritional assessments, is recommended, and should be designed to avoid weight loss or gain and minimize the consequences of gastrointestinal dysfunction. as the disease advances, swallowing difficulties (dysphagia) may appear. using thickening agents for liquid intake and an upright posture when eating may be useful; both measures reduce the risk of choking. gastrostomy can be used to deliver food directly into the stomach. levodopa and proteins use the same transportation system in the intestine and the blood–brain barrier, thereby competing for access. taking them together results in reduced effectiveness of the drug. therefore, when levodopa is introduced, excessive protein consumption is discouraged in favour of a well-balanced mediterranean diet. in advanced stages, additional intake of low-protein products such as bread or pasta is recommended for similar reasons. to minimize interaction with proteins, levodopa should be taken 30 minutes before meals. at the same time, regimens for pd restrict proteins during breakfast and lunch, allowing protein intake in the evening. prognosis