Vol. 13, Issue 5 (2025)
Next-generation neurotransmitter-based drugs for Parkinson’s disease: Organic design and delivery challenges
Author(s): Lalita Kumari
Abstract: Parkinson's disease (PD), a leading neurodegenerative disorder, involves progressive loss of dopaminergic neurons in the substantia nigra pars compacta, causing dopamine depletion and motor (e.g., bradykinesia, tremor) and non-motor symptoms. Current treatments like levodopa (L-DOPA) and dopamine agonists provide symptomatic relief but do not stop progression or prevent complications such as motor fluctuations and dyskinesia. This review examines next-generation neurotransmitter-based drugs, emphasizing engineered analogs and prodrugs from dopamine, serotonin, and norepinephrine to better restore neurotransmitter balance. Organic synthesis challenges include ensuring stereochemical purity, boosting metabolic stability, and using bioisosteric modifications for enhanced receptor affinity with reduced off-target effects. For example, DAD9 conjugates dopamine precursors with neuroprotective agents, merging symptomatic and disease-modifying benefits via advanced synthetic methods. A major obstacle is blood-brain barrier (BBB) delivery, which blocks polar neurotransmitter mimics. Promising strategies include nanoparticle encapsulation (e.g., PLGA systems) and receptor-mediated transcytosis, offering sustained release and targeted neuronal uptake in preclinical models. Yet, issues like synthesis scalability, nanocarrier immunogenicity, and pharmacokinetic variations in elderly patients persist. The paper explores the synergy of organic chemistry, pharmacology, and nanotechnology, advocating hybrid solutions like lipid-peptide conjugates for BBB crossing. Leveraging computational modeling and high-throughput screening accelerates lead development. These drugs could transform PD care from palliative to neuroprotective, safeguarding motor and cognitive functions. Addressing these hurdles calls for integrated clinical trials to confirm efficacy and safety.
DOI: 10.22271/chemi.2025.v13.i5a.12591
Pages: 44-51 | 957 Views 147 Downloads
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How to cite this article:
Lalita Kumari. Next-generation neurotransmitter-based drugs for Parkinson’s disease: Organic design and delivery challenges. Int J Chem Stud 2025;13(5):44-51. DOI: 10.22271/chemi.2025.v13.i5a.12591
