Parkinson's disease is a degenerative disorder of the central nervous system. The earliest symptoms are related to movement and including a tremor, rigidity, slow movements and difficulty walking. Later symptoms can include thinking, sleep, emotional and behavioral problems including dementia. The exact cause is unknown, but both genetic and environmental factors appear to play a role. These factors lead to the death of dopamine-containing nerves in a part of the mid brain called the substantia nigra pars compacta. Dopamine and acetylcholine both have roles in this area of the brain. It is important to consult a physician for the diagnosis and management of Parkinson's disease.
Dopamine is released in many areas in the brain; however, there are four major pathways. The mesolimbic pathway is involved in reward and reinforcement. The mesocortical pathway helps to regulate emotional response and motivation. The tuberoinfundibular pathway helps to regulate the hormone prolactin. The nigrostriatal pathway helps produce movement and is the primary pathway affected in Parkinson's disease. After the loss of 80 percent or more of the nerve cells in the substantia nigra, symptoms of Parkinson's disease will develop. The mechanism underlying the loss of these dopamine cells is unknown.
The most common medicine used to treat Parkinson's disease is levodopa. Unlike dopamine, levodopa is able to cross the barrier between the blood and brain. It is converted into dopamine by an enzyme called dopa-decarboxylase in the brain, and can replace some of the lost dopamine. It is given with the drug carbidopa, which inhibits dopa-decarboxylase outside of the brain, decreasing the conversion of levodopa to dopamine in the body, and thus decreasing side-effects. Dopamine agonists such as bromocriptine bind to nerve cells and mimic the actions of dopamine. MAO-B inhibitors decrease the metabolism of dopamine.
In the central nervous system, acetylcholine helps with attention, arousal, reward and sensation among other functions. In the normal midbrain, there is a balance between dopamine and acetylcholine. The loss of dopamine tilts the balance toward too much acetylcholine, which also contributes to motor symptoms.
Acetylcholine medications for Parkinson's disease are called anticholinergics. They block the signalling of acetylcholine to help restore the balance of dopamine to acetylcholine. These drugs are more often used in younger people and help more with symptoms such as tremor rather than slowed movement. Common side-effects may include dry mouth, GI upset, blurry vision, sleepiness and increased heart rate.
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