Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Volume 25, Issue 3, 2025

Brain ischemia occurs following heart failure, thromboembolism, and atherosclerosis, and it is characterized by the disturbance of blood flow resulting from the blockage of blood vessels. After a series of studies, it is deduced that various changes occur following stroke, including neural death and changes in plasticity. Studies have reported that neurotransmitters tend to change following stroke. These changes that occur surrounding the infarct area following stroke can be considered new therapeutic targets for stroke rehabilitation. Although various studies have reported that different neurotransmitters have a promising role in either the progression or the rehabilitation following stroke, they have not found any pharmacological interventions to help the previous rehabilitation therapeutics. Phytocompounds also offer potential therapeutic benefits in stroke management due to their antioxidative and anti-inflammatory properties. This article aimed to compile recent advancements in neurotransmitter research related to ischemia and explore the potential use of neurotransmitter agonists/antagonists in ischemic conditions to identify potential drug candidates for treating the severe and prolonged stages of stroke in the future.

Multiple sclerosis (MS) is an unceasing, demyelinating, idiopathic inflammatory, and neurodegenerative disease of the Central Nervous System (CNS.) The disease is characterized by the occurrence of neurological symptoms over a period of days to weeks, abide by partial or absolute diminutions of various durations.

In this review, a concise outline on disease activity and progression of MS, pathogenesis with the special prominence on the biomarkers for the MS as therapeutic targets has been discussed by carrying out a comprehensive literature survey employing chief websites and search engines for investigation. Cortical inflammation, neurodegeneration, demyelination, axonal injury, axonal loss, oligodendrocytes, mitochondrial dysfunction, microglia activation, oxidative and nitrosative stress are the pathological hallmarks of the MS. CNS neurofilaments, chitinase and chitinase 3-like proteins, soluble circulating form (sCD163), Chemokine ligand 13 (CXCL13), immunoglobulin M, MicroRNA (miRNA) and messenger Ribonucleic Acid (mRNA), Glial fibrillary acidic protein (GFAP), serum osteopontin, 8-iso-prostaglandin F2α (8-iso-PGF2 α), apo-Lipoprotein E and myelin-reactive T cells are some of the therapeutically valuable biomarkers for such multifarious disorder.

MS is one of the chronic neurodegenerative diseases with undefined etiology. The study of the pathophysiology of the disease and the involvement of certain biomarkers can help identify new targets for therapeutic intercession, identify individuals at risk of developing the disease later in life, and allow more effective treatment of progressive diseases such as MS.

Liposomal drug delivery methods are becoming increasingly viable options for improving treatment outcomes for neurological illnesses. These systems provide a flexible framework for the formulation of medications intended for delivery to the brain, protecting the medication from enzymatic breakdown and enhancing its bioavailability. To maximize liposome-drug interactions and improve brain-targeted delivery efficiency, a variety of formulation strategies are used, such as surface modification and remote loading. By utilizing various pathways to cross the blood-brain barrier (BBB), such as passive diffusion and receptor-mediated transcytosis, liposomes facilitate the effective transport of therapeutic drugs to the brain parenchyma. Liposomal formulations show potential for targeted drug delivery, reducing off-target effects, and improving treatment efficacy in neurological conditions like Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis, and brain cancers. For instance, in Parkinson's disease, liposomal delivery of neuroprotective agents can help maintain dopamine levels and protect dopaminergic neurons. In Alzheimer's disease, liposomes can be engineered to deliver drugs that reduce amyloid-beta plaques or tau tangles. For brain cancer, liposomal chemotherapy can target tumor cells more precisely while minimizing damage to surrounding healthy tissue. In stroke, liposomal delivery of neuroprotective agents can reduce the extent of brain damage, while in multiple sclerosis, liposomes can be used to deliver drugs that modulate the immune response. However, the clinical translation of liposomal drug delivery systems for brain diseases faces challenges related to scalability, stability, and immunogenicity, in addition to regulatory barriers. Scalability issues arise from the complex manufacturing processes required to produce liposomes consistently on a large scale. Stability concerns involve maintaining the integrity of liposomes during storage and after administration. Immunogenicity can be a problem if the liposomes trigger an unwanted immune response, potentially reducing their effectiveness or causing adverse effects. To overcome these obstacles, multidisciplinary cooperation is essential. Collaboration among materials scientists, pharmacologists, neurologists, and regulatory experts can drive the development of more robust liposomal formulations. Continuous research is needed to refine liposome designs, such as by optimizing lipid composition, surface charge, and size to improve stability and targeting capabilities. Advanced techniques like PEGylation (coating liposomes with polyethylene glycol) can help reduce immunogenicity and extend circulation time in the bloodstream. Despite these challenges, liposomal methods present intriguing prospects for transforming medication administration to the brain and offering effective treatments for neurological illnesses. The development of more sophisticated liposomal technologies, combined with a deeper understanding of their mechanisms of action, could lead to significant breakthroughs in the treatment of neurological disorders. For example, research into ligand-targeted liposomes, which use specific molecules to bind to receptors on the BBB, holds promise for enhancing delivery specificity and efficiency. To fully realize the therapeutic promise of these novel drug delivery systems, further advancements in liposomal technologies and a deeper understanding of their mechanisms are necessary. This includes not only technical improvements but also comprehensive preclinical and clinical studies to evaluate safety, efficacy, and long-term effects. As our knowledge expands and technology progresses, liposomal drug delivery could become a cornerstone of neurological disease treatment, providing new hope for patients with previously intractable conditions.

Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the blood-brain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.

More than 20 million people worldwide have Alzheimer's disease (AD), making it the most prevalent disease. Patients with AD may live for at least a decade after diagnosis, making it the most common cause of disability in the elderly. Each year, 1% to 4% of the population is affected by AD, with prevalence peaking between ages 65 and 70 and declining to 6% among those over 85. Researchers have accumulated evidence on medicinal herbs that may reverse the pathogenesis of Alzheimer's disease. Alzheimer's disease (AD) is associated with severe memory loss, which can negatively impact social and professional life. The first neurotransmitter linked to Alzheimer's was acetylcholine (ACh). There is no known cure, and the available treatments are ineffective. Multiple studies indicate that Ayurvedic restorative herbs and their constituents may be effective in treating Alzheimer's disease. This technique emphasizes the fact that delaying or preventing Alzheimer's disease with the help of natural bio-actives could reduce the number of cases over the next half-century. To provide detailed information, the pathology and pathophysiology of Alzheimer's Disease are discussed in the text of this review, along with an overview of the neurotransmitters involved in the progression of the disease. The importance of different natural bio-actives for the treatment of Alzheimer's disease is also outlined in the paper. The information contained in this paper can serve as a template for future research expressing the more beneficial role of other bioactive in acting as an adjuvant in the prevention and treatment of this disease, facing certain challenges and gaps with conventional drugs used to treat Alzheimer's disease.

Mild Cognitive Impairment (MCI) is swiftly emerging as a prevalent clinical concern within the elderly demographic. Willoughby spearheaded the pioneering investigation into the evolution of memory decline spanning from the age of 20 to 70. Employing a computerized substitution examination, he pinpointed a zenith in memory prowess at the age of 22, signifying the shift from infancy, succeeded by a gradual decline in later years in 1929. Cognitive impairment impacts various facets, encompassing cognition, memory, perceptual acuity, and linguistic proficiency. Compelling evidence indicates that genetic, dietary, and metabolic factors influence the trajectory of cognitive decline in this patient cohort. In addition to the widely recognized influence of the Mediterranean diet on cognitive function, numerous studies have delved into the potential impact of diverse phytochemicals on cognitive deterioration. Many of these compounds are renowned for their inflammation reducer or free-radical scavenger properties, coupled with their commendable acceptability and defense profiles. Phytochemicals sourced from medicinal plants play an essential role in upholding the intricate chemical equilibrium of the brain by modulating receptors linked to crucial inhibitory neurotransmitters. Across the annals of historical medicinal traditions, a multitude of plants have been cataloged for their efficacy in mitigating cognitive disorders. This study presents a concise examination of distinct medicinal herbs, highlighting their neuroprotective phytochemical components such as fatty acids, phenols, alkaloids, flavonoids, saponins, terpenes, and beyond. The principal objective of this inquiry is to meticulously inspect and provide discernment into the extant evidence concerning phytochemicals exhibiting clinically demonstrable effects on cognitive decline.

Migraine is one of the most painful and debilitating conditions, which is characterized by a pulsating headache. Many therapeutic strategies are being used to prevent and treat the symptoms and underlying pathology. A relatively high number of different medications are currently being used for migraine prevention in clinical practice. However, these compounds were initially developed for other indications and were different in their mechanisms of action. This review mainly summarized all the conventional and phytocompounds currently present for the treatment of migraine. Further, we also discussed therapeutic potential and clinical studies of natural compounds for the treatment of migraine prophylaxis under various chemical categories like flavonoids, polyphenols, alkaloids, glycosides, terpenoids, and lactone, acid, and alcohol.

One percent of persons over 65 years of age suffer from Parkinson's disease, a neurological ailment marked by dopaminergic neurons in the nigrostriatal pathway gradually dying and being depleted in the striatum. Parkin and PINK1 gene mutations, which are essential for mitophagy and impair mitochondrial function, are the cause of it. Parkinson's disease is linked to a number of motor and impairment disorders, including bradykinesia, rigid muscles, tremor at rest, and imbalance. Numerous signaling pathways, including α-synuclein aggregation, lead to age-related decline in proteolytic defense systems. Parkinson's disease etiology involves oxidative stress, ferroptosis, mitochondrial failure, and neuroinflammation. Parkinson's disease is significantly influenced by neuroinflammation, which is a result of both innate and adaptive immune responses. The purpose of studying mechanisms and phytomolecules is to assist researchers in creating therapies for Parkinson's disease. Phytomolecules, like curcumin, β-amyrin, berberine, capsaicin, and gentisic acid, exert neuroprotective properties by reducing ROS levels, lessening α-synuclein-induced toxicity, and shielding the cells from apoptosis. In conclusion, the studies presented here provide valuable insights into the potential of various medications for Parkinson's disease treatment. By understanding the mechanisms behind these treatments, researchers can develop more effective treatments for PD.