Central nervous system agents in medicinal chemistry最新文献

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 bloodbrain 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.

The accumulation of tau-containing neurofibrillary tangles and beta-amyloid deposits has been identified as the hallmark of Alzheimer's disease. Alzheimer's disease (AD) is a hereditary and neurological condition that can result in non-amnestic cognitive decline in less common forms and amnestic memory loss in its classic form. While Alzheimer's disease is the most prevalent cause of memory loss in middle-aged and older adults, other neurodegenerative and cerebrovascular disorders can have an impact on the disease's clinical course. Designing multi-target-directed ligands (MTDLs) is a very promising modern approach. This methodology was designed specifically for treating disorders with complex pathological mechanisms. Among these disorders is Alzheimer's disease (AD), which is currently the most prevalent multifactorial neurodegenerative illness. Increased amounts of the amyloid βpeptide (Aβ) and hyperphosphorylated tau protein, together with the loss of neurons and synapses, are linked to Alzheimer's disease (AD). Additionally, there is evidence that the pathophysiology of this condition is influenced by oxidative stress, metal ion dysregulation, inflammation, and failure of the cell cycle regulatory system. Since Alzheimer's disease (AD) is a multi-factor illness, there are many attractive targets for the development of anti-AD medications. These molecules can be useful in treating AD since they are multi-target-directed. This review focuses on the discovery of dual and multi-acting anti-AD drug candidates, especially hybrids made by combining chemically active moieties that function against distinct targets. The first group of substances consists of cholinesterase inhibitors with extra properties or those that function as multiple binding site inhibitors. Natural products also provide numerous options for slowing the progression and symptoms of many diseases, including Alzheimer's Meanwhile, Natural chemical structures with the following characteristics: alkaloids, sterols, triterpenes, tannins, flavonoids, polyphenols, and antioxidants as well as anti-inflammatory and anti-amyloidogenic properties. We provide an overview of Alzheimer's disease pathophysiology and therapy targets in this study. We also show several isolated chemicals and medicinal plants that are used to treat and prevent the symptoms of Alzheimer's disease.

Recently, traumatic brain injury (TBI) has been a growing disorder due to frequent brain dysfunction. The Glasgow Coma Scale expresses TBI as classified as having mild, moderate, or severe brain effects, according to the effects on the brain. Brain receptors undergo various modifications in their pathology through chemical synaptic pathways, leading to depression, Alzheimer's, and Parkinson's disease. These brain disorders can be controlled using central receptors such as dopamine, glutamate, and γ-aminobutyric acid, which are clearly explained in this review. Furthermore, there are many complications in TBI's clinical trials and diagnostics, leading to insignificant treatment, causing permanent neuro-damage, physical disability, and even death. Bio-screening and conventional molecular-based therapies are inappropriate due to poor preclinical testing and delayed recovery. Hence, modern nanotechnology utilizing nanopulsed laser therapy and advanced nanoparticle insertion will be suitable for TBI's diagnostics and treatment. In recent days, nanotechnology has an important role in TBI control and provides a higher success rate than conventional therapies. This review highlights the pathophysiology of TBI by comprising the drawbacks of conventional techniques and supports suitable modern alternates for treating TBI.

Background: A Non-Ergot Dopamine Agonist (NEDA) rotigotine has been designed as a new transdermal drug delivery system.

Aim: To maintain optimum homogeneity in drug content, the rotigotine transdermal patch was developed utilizing a solvent casting technique.

Methods: The characteristics of a transdermal patch, including patch weight, folding endurance, patch thickness, surface morphology, tensile strength, swelling rate, surface pH, in vitro release studies, water retention rate, uniformity of drug content, and ex-vivo permeation studies, were determined.

Results: In vitro drug release studies unequivocally demonstrated that drug release controlled polymer interactions. There was no apparent lag period before the drug release rate started to decline. The developed patch showed 70 ± 1.18 % of prolongation of drug release within 24 hours. The result of the penetration studies demonstrated that 61 ± 2.52% of rotigotine permeated through the epidermal barrier within 24 h.

Conclusion: The developed transdermal patch comprising rotigotine was evidently placed on the dermis layer, and an appropriate dose was delivered into circulation for a longer time based on the aforementioned factors. The findings of this study illustrate the effective approach of transdermal patches to treat Parkinson's disease.

Background: Camellia sinensis has an extensive variety of pharmacological properties, including neuroprotection, photo-aging resistance, stress resistance, antioxidant, anti-tumour, hypoglycemic, antibacterial, and antiviral effects tracing a good potential in addressing illness and preventing disease. Challenges with conventional dosage forms include patient incompatibility, improper dosing, the inclusion of microplastics, etc. Objective: The present work aims to deliver a novel formulation devoid of microplastics and with improved consumer compliance.

Methods: Wet granulation was used to formulate 500 mg Camellia sinensis effervescent tablets, with improved effervescent time and rapid release. Citric acid and sodium bicarbonate's impacts on disintegration time and pH were examined using a factorial design. Pre-compression variables were assessed for the granule mixture. Post-compression criteria were employed to assess effervescent tablets. The optimum formulation was selected using a central composite response surface and assessment criteria.

Results: The physicochemical characteristics of the developed formulations were significantly influenced by the independent factors. Low concentrations of sodium bicarbonate have positive impact on pH whereas high concentrations of sodium bicarbonate as well as citric acid enhance disintegration time. The design outcomes showed that the optimized effervescent tablets (F10) prepared with 697.5 mg and 448.38 mg of citric acid and sodium bicarbonate respectively had good physicochemical properties.

Conclusion: In compliance with present quality standards, factorial design was efficiently utilized for the development of Camellia sinensis effervescent tablets. It was concluded that green tea effervescent tablet (F10) would function as a substitute for conventional green tea powder along with green tea bags as a means of administration.

Introduction: Tuberculosis (TB) is the most common disease that affects the lungs, and it is associated with Mycobacterium tuberculosis infection. Many synthetic medications, such as pyrazinamide, isoniazid, and ethambutol, are available to treat TB; however, their adverse effects are severe. Medicinal herbs have lately become popular, safe, and effective alternative treatments for TB.

Methods: The purpose of this systematic review was to assess the possible use of natural plants in the development of herbal treatments and remedies for TB by studying the medicinal plants and phytochemicals that have been used for the disease. Information was gathered from a variety of sources, including Bentham, Elsevier, Springer, Nature, Google Scholar, PubMed, Sci- Finder, and the Web of Science. For the investigation, common and scientific names of plants, as well as terms like "mycobacterium tuberculosis," "herbal plants," "flavonoids," and "alkaloids" were employed. In the end, 376 plants belonging to 83 families were discovered, and details about each plant family, as well as the section of the plant utilized, chemical components, extract, and strain, were extracted.

Results: The findings showed that although flavonoids and alkaloids were the most prevalent naturally occurring substances found in plants, the Fabiaceae family had a greater potential to eradicate TB.

Conclusion: The leaf portion was shown to be more active, and the S-37 RV strain of Mycobacterium TB was employed more frequently.

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.

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.