Pharmacological strategies in managing Parkinson’s disease: Beyond dopaminergic agents

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by motor symptoms due to dopaminergic neuron loss. While dopaminergic agents such as levodopa and dopamine agonists have been cornerstone therapies, their long-term efficacy diminishes and is often accompanied by significant side effects. This review focuses on non-dopaminergic pharmacological strategies that offer potential alternatives or adjuncts to traditional therapies. Key areas explored include the role of glutamatergic, serotonergic, and adenosinergic systems in PD management. The review examines the therapeutic potential of glutamate antagonists, serotonin-reuptake inhibitors, and adenosine A2A receptor antagonists in mitigating motor and non-motor symptoms. In addition, it covers recent advancements in targeting neuroinflammation and neuroprotection as adjunctive therapies. Emerging treatments such as gene therapy, neurotrophic factors, and novel small molecules are also discussed, highlighting their mechanisms of action and clinical trial outcomes. By providing a comprehensive overview of these non-dopaminergic approaches, the review aims to offer insights into innovative treatment strategies that could improve symptom management and quality of life for PD patients, potentially addressing the limitations of current dopaminergic therapies.