Therapeutic Approaches to Restore Dopamine Homeostasis and Alleviate Motor Symptoms in Parkinson’s Disease – a Narrative Review

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by progressive dopaminergic neuronal loss in the substantia nigra pars compacta, leading to motor impairments such as bradykinesia, tremors, and rigidity. Current therapeutic strategies aim to restore dopamine homeostasis and alleviate motor symptoms through pharmacological, surgical, and non-pharmacological interventions; however, there is no current treatments that treat PD as a whole. This narrative review highlights three primary pharmacological approaches: (1) dopamine replacement with levodopa, the gold standard therapy, which is effective but associated with long-term complications such as motor fluctuations and dyskinesias; (2) dopamine receptor agonists, which offer an alternative to levodopa but exhibit increased non-motor side effects; and (3) inhibitors of dopamine degradation enzymes, including monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors, which prolong dopamine availability and reduce motor fluctuations. Emerging strategies focus on multifunctional compounds targeting both MAO-B and COMT, offering neuroprotection and improved dopaminergic stability. Despite advancements in PD management, an urgent need remains for novel therapeutics that provide sustained symptom relief with minimal side effects.