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Bioinformatics of the Brain

converted to dopamine. Bradykinesia and stiffness can be effectively reduced

with levodopa treatment, yet early onset of the disease, prolonged illness,

and prolonged levodopa administration are risk factors for the development of

dyskinesia [64, 65]. PD patients may experience variations in their motor func-

tion and a progressive reduction in the duration of a single levodopa dosage

(wearing-off phenomena) following years of stability with the medication. In

more severe situations, episodes of immobility occur for whatever length of

time that levodopa is taken. PD patients are also treated with dopamine re-

ceptor agonists, which stimulate postsynaptic dopamine receptors to enhance

dopaminergic transmission [65].

While senior individuals are more vulnerable to the neuropsychiatric side

effects of other anti-Parkinsonian medications, they are also less likely to ex-

perience motor issues from levodopa. For this reason, it is more advisable to

start levodopa usage early in the older population. Levodopa can be used for

both standard and controlled releases when initiating treatment [66]. Con-

trary to expectations, however, there was no evidence to back up the theory

that the controlled release type can stop the onset of motor problems. The

absorption of the controlled-release formulations is irregular, and their effec-

tiveness is roughly two-thirds to three-quarters that of a typical tablet. This

is because levodopa is only absorbed from the small intestine, and even then,

only a portion of the levodopa in the slow-release pill is released into the large

intestine. It’s common practice to take slow-releasing levodopa right before

bed. As a result, mobility is offered for an extended amount of time while

you sleep [67]. The basis of pharmacokinetic problems is that levodopa is a

neutral amino acid. Therefore, it competes with other amino acids both dur-

ing intestinal absorption and during blood-brain barrier passage. If it is taken

with protein-rich food, the amount transferred to the brain decreases and

therefore the clinical efficacy is weakened. The best efficacy for levodopa is

achieved when taken on an empty stomach [64]. In the postrema region, where

the blood-brain barrier is absent, peripheral dopamine induces both nausea

and vomiting. It also causes peripheral dopaminergic side effects which af-

fect the cardiovascular system resulting the abnormalities such as orthostatic

hypotension and arrhythmia.

Dopamine receptor agonists are medications to stimulate postsynaptic

dopamine receptors to lower symptoms; they accomplish this without me-

tabolizing dopamine and are therefore not affected by the neurodegenerative

process. Dopamine agonists are preferred over levodopa due to their effective-

ness to treat PD symptoms and lowered risk of the development of motor

impairments. While monotherapy with dopamine agonists is successful, the

percentage of patients who actively use it decreases over time and drops below

20% after a few years of treatment [68, 69]. For this reason, most individuals

are given additional treatments—typically levodopa—after receiving medica-

tion for a few years. Neuralgia, vomiting, and orthostatic hypotension are ex-

amples of peripheral dopaminergic adverse effects that typically manifest early

in treatment and improve with time. However, at first, the medication must