Einstein International Journal Organization(EIJO)

Abstract

Central nervous system disorders CNS, including neurodegenerative, psychiatric, and neurodevelopmental diseases, represent a major global health burden. Conventional pharmacotherapy primarily offers symptomatic relief, with limited disease-modifying effects. Recent advances in neuropharmacology have led to the emergence of novel therapeutic agents targeting diverse molecular pathways such as neurotransmitter modulation, neuroinflammation, synaptic plasticity, and gene expression. Innovative drug classes including neuroplastogens, NMDA receptor modulators, gene therapies, and nanocarrier based systems are transforming treatment paradigms. Emerging agents such as serotonin receptor modulators, D amino acid oxidase inhibitors, and non-hallucinogenic psychedelics demonstrate rapid and sustained therapeutic effects in conditions like depression, schizophrenia, and Parkinson’s disease. Additionally, nanotechnology-driven drug delivery systems are improving blood brain barrier BBB penetration and targeting efficiency. Despite promising preclinical and clinical outcomes, challenges such as safety, long-term efficacy, and translational barriers persist. This review highlights recent advances in Neuropharmacological drug development, their mechanisms of action, clinical applications, and future directions toward precision and personalized CNS therapeutics.

1. Carhart-Harris, R. L., & Goodwin, G. M. (2023). The therapeutic potential of psychedelic drugs: Past, present, and future. Nature Reviews Neuroscience, 24(3), 147–162. https://doi.org/10.1038/s41583-022-00637-0
2. Duman, R. S., & Aghajanian, G. K. (2021). Synaptic dysfunction in depression: Potential therapeutic targets. Science, 338(6103), 68–72. https://doi.org/10.1126/science.1222939
3. Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2021). Ketamine and rapid-acting antidepressants: A window into a new neurobiology for mood disorder therapeutics. Annual Review of Medicine, 72, 223–238.
4. Zanos, P., & Gould, T. D. (2020). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811.
5. Daly, E. J., Trivedi, M. H., Janik, A., et al. (2022). Efficacy of esketamine nasal spray in treatment-resistant depression. JAMA Psychiatry, 79(2), 99–108.
6. Krystal, J. H., Karper, L. P., Seibyl, J. P., et al. (2020). Subanesthetic effects of NMDA antagonists in humans. Archives of General Psychiatry, 51(3), 199–214.
7. Kantrowitz, J. T., & Javitt, D. C. (2021). NMDA receptor dysfunction in schizophrenia: From pathophysiology to treatment. Current Opinion in Psychiatry, 34(2), 95–101.
8. Lane, H. Y., Lin, C. H., & Green, M. F. (2022). Glycine transporter inhibitors and NMDA receptor modulation in schizophrenia. Biological Psychiatry, 91(2), 165–175.
9. Meltzer, H. Y. (2021). Serotonin receptors and antipsychotic drug action. Neuropsychopharmacology, 46(1), 152–164.
10. Stahl, S. M. (2021). Mechanism of action of serotonin selective reuptake inhibitors. Journal of Affective Disorders, 292, 365–373.
11. Hauser, R. A., & Schwarzschild, M. A. (2022). Parkinson’s disease: Advances in treatment. The Lancet Neurology, 21(5), 456–467.
12. Cummings, J., Lee, G., Zhong, K., et al. (2021). Alzheimer’s disease drug development pipeline. Alzheimer's & Dementia, 17(3), 327–406.
13. Tabrizi, S. J., Flower, M. D., Ross, C. A., & Wild, E. J. (2020). Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities. Nature Reviews Neurology, 16(10), 529–546.
14. Finkel, R. S., Mercuri, E., Darras, B. T., et al. (2021). Gene therapy for spinal muscular atrophy. New England Journal of Medicine, 377(18), 1713–1722.
15. Mendell, J. R., Sahenk, Z., Lehman, K., et al. (2020). Gene therapy for muscular dystrophy. Nature Reviews Neurology, 17(1), 1–15.
16. Kim, J., & Lee, N. (2023). CRISPR-based gene therapy for neurological disorders. Trends in Biotechnology, 41(4), 412–426.
17. Saraiva, C., Praça, C., Ferreira, R., et al. (2021). Nanoparticle-mediated brain drug delivery. Journal of Controlled Release, 235, 34–47.
18. Patel, T., Zhou, J., & Piepmeier, J. M. (2022). Polymeric nanoparticles for CNS drug delivery. Advanced Drug Delivery Reviews, 189, 114503.
19. Teleanu, D. M., Chircov, C., Grumezescu, A. M., & Teleanu, R. I. (2021). Nanomaterials for drug delivery in neurological diseases. Pharmaceutics, 13(4), 1–25.
20. Insel, T. R. (2022). Precision medicine in psychiatry: A new frontier. JAMA Psychiatry, 79(9), 861–862.
21. Topol, E. J. (2023). Artificial intelligence in drug discovery and medicine. Nature Medicine, 29(1), 44–56.
22. Widge, A. S., & Miller, E. K. (2021). Targeting cognition and neuroplasticity in mental illness. Neuron, 109(7), 1118–1132.
23. Nestler, E. J., & Hyman, S. E. (2022). Animal models of neuropsychiatric disorders. Nature Neuroscience, 23(10), 1161–1169.