Abstract:
Introduction. Parkinson's disease is a long-term neurodegenerative condition of the central
nervous system that mainly affects the control of voluntary movements due to the gradual
degeneration of dopaminergic neurons in the substantia nigra region of the brain. The treatment
of Parkinson's disease has improved continuously, with a strong focus on developing innovative
methods to effectively manage the complexities of this disorder for each patient.
Aim of study. To explore the most recent concepts of Parkinson’s disease pharmacotherapy based
on the pathophysiological mechanism at the central nervous system (CNS) level.
Methods and materials. The current review involved carefully selecting and examining a curated
set of academic literature from electronic databases such as HINARI, PubMed, NCBI, and
ScienceDirect.
Results. Parkinson's disease treatment still relies on Levodopa (LD) as the gold standard. Despite
this, prolonged use of levodopa has been shown to result in motor complications, known as the
"on-off phenomenon", in most patients. Peripheral metabolism of LD (plasma circulating level
fluctuations) may lead to systemic effects, including cardiac arrhythmias, hypotension, and
vomiting. Modern strategies have been formulated to synthesize LD and dopamine prodrugs (ester,
amide, cyclic prodrugs, also chemical delivery systems, enzyme models), aiming to maintain LD's
effectiveness while reducing side effects. Add-on oral therapies like dopamine agonists (DAAs),
monoamine oxidase Type-B inhibitors (MAO-B Is), and COMT inhibitors (COMT-Is), along with
amantadine ER and adenosine A2A receptor antagonists (AA2AA), were developed to improve
life expectancy and enhance the long-term response to LD therapy. In recent years, researchers
have studied iron chelators as neuroprotective agents. The dopaminergic neurons of the CNS
contain a significant amount of neuromelanin (NM), a dense and insoluble pigment with a strong
affinity for iron. The chelator's removal of iron will prevent the excessive formation of reactive
oxygen species, which leads to neuroinflammation.
Conclusion. The diligent research and continuous improvement of drug treatment for Parkinson's
disease lead to a major improvement in patients' quality of life. Recreating the enzyme model in
prodrug synthesis can improve the pharmacokinetic and pharmacodynamic properties, resulting in
a successful drug delivery system that specifically targets them to the substantia nigra. Recent
studies also investigate the potential neuroprotective role of iron chelators in management of
Parkinson's disease.
