The transport of CNS acting drugs across blood-brain barrier is complex and guided by the molecular weight, PH, physicochemical and pathological state of the BBB among others. In view of this, literatures were assessed for possible conversion of Non-CNS to CNS acting drugs, whose ability to penetrate CNS can be improved using polymers for biomedical applications. The findings have shown that compounds with pyridine, pyrrole, carboxamide, pyridone among others can be converted to CNS acting drugs that can be loaded in specialized carrier polymers for transportation across BBB. Read More
Background: Mannich bases are known to be an important pharmacophore or bioactive leads in the synthesis of various potential agents that have a variety of therapeutic activities like anticancer, antipsychotic, anticonvulsant, antimalarial, anti-inflammatory, antibacterial and so forth. Thus, in the present research, conjugation of moieties like 1,5-benzoxazepines and 1,5-benzothiazepines with secondary amines like piperazine, methyl piperazine and morpholine was carried out in a Mannich base with an anticipation of good anticonvulsant activity.
Objective: Synthesis, characterization, structure activity relationship and anticonvulsant activity of the Mannich bases of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. Read More
A series of novel diazaspiro compounds 6a-t were synthesised and biologically evaluated for their anticonvulsant activity in the maximal electroshock seizure (MES) assay. Most of the tested compounds exhibited moderate to weak activity in the MES screen test, The compounds 6f, 6h, 6i, 6j, 6p, 6s and 6n able to protect seizure effect significantly higher and this effect was similar when compared to standard drug treated rats. Read More
Central nervous system (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identifying functional chemical groups that may serve as lead molecule for synthesis of compounds that may have CNS activity. Read More
The benzoxazepine JL13 is an analogue of the clozapine family which targets the 5-HT2A receptor, and has showed promise as an atypical antipsychotic agent. Following structure function analysis with a series of synthetic analogues, homology modeling was performed to determine key interaction sites with the receptor. An aza analogue was synthesized for evaluation, and demonstrated seventeen times greater affinity for the receptor. Read More
Amyloid fibrils represent stable form of many misfolded proteins associated with numerous diseases like Parkinson's disease(PD),Type II diabetes and Alzheimer's disease(AD). Lewy Bodies(LB) are the pathological hallmark of PD where long fibrils disrupting the brain's activity that constitutes the main component, α-synuclein. However α-synuclein structure has eluded researchers due to its complexity, insolubility and difficulty of characterizing one protein within a fibril. Read More
A series of new N-(2-benzoyl-4-chlorophenyl)-2-(4-(substituted phenyl) piperazin-1-yl) acetamides (3a-j) have been synthesized by the chloroacetylation of 2-amino-5-chlorbenzophenone which was further reacted with substituted phenylpiperazine. The chemical structures of the compounds were confirmed on the basis of their TLC, IR, 1HNMR, 13CNMR and by elemental analysis. The physicochemical similarity of the target compounds with respect to standard drug diazepam was assessed by calculating from a set of physicochemical properties using software programs. Read More
Background: Chronic arsenic-exposure even at a low-dose results in the neural impairment and motor/cognitive dysfunction. However, several preventive approaches are made mainly against hepatic/gastrointestinal damages. Only a few investigations postulate therapeutic strategies for neural anomalies. Read More
Background: According to World Health Organization (WHO), around 50 million people worldwide suffering from epilepsy. Therefore, continued search for safer and more effective anticonvulsants is urgently necessary.
Objectives: The present work was to synthesize 2-phenyl substituted quiazolinone derivatives and to evaluate them for anticonvulsant activity and neurotoxic. Read More
Piroxicam has been reported to be convertible to central nervous system (CNS) acting agents. It has serious depressant effects at high doses. In view of this structures of piroxicam metabolites were assessed for possible conversion to CNS depressants. Read More
Background: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. Read More
Background: In 2016, the statistical reports stated that Alzheimer is not just memory loss but it kills and has become the 6th leading cause of death. The number of dementia patients is increasing rapidly and expected to rise to 131.5 million by 2050. Read More
This overview is aimed at reevaluating fundamental approaches of current MS therapies with focus being placed on their targeted underlying immune, molecular and cellular mechanisms. Currently used therapies are discussed in regard to their mechanisms of action, clinical accomplishments and unwanted side effects and complications. Special emphasis is given to current disease modifying therapies (DMT) and their actions at immune mechanisms of disease. Read More
Background: The nicotinic acetylcholine receptor (nAChR) gene family encodes for subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many functions: They mediate excitation at neuro-muscular junctions. Nicotinic Acetylcholine Receptor: In the central nervous system nAChRs have been implicated in memory, cognition, and addiction. Read More
Background: Thymol (THY), which is a monocyclic monoterpene, found in oil of thyme various other kinds of plants. Until today, although different biological properties of THY have been indicated, its neurological toxicity has never been investigated.
Method: In this study, in vitro antiproliferative (by 3-(4,5 dimetylthiazol-2-yl)-2,5 diphenlytetrazolium bromide (MTT) test), genotoxic (by single cell gel electrophoresis (SCGE)) and oxidative effects (by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis) of THY (0-400 mg/L) were assessed on cultured primary rat neurons (CPRNs) and N2a neuroblastoma cells. Read More
Background: MRJF4, a novel haloperidol metabolite II prodrug, was obtained through the esterification of the secondary hydroxyl group of haloperidol metabolite II with 4-phenylbutyric acid. The activities of (±)-MRJF4 and its two enantiomers [(+)-MRJF4 and (-)-MRJF4] as tumor specific inducers of pro-apoptotic genes were evaluated on malignant C6 glioma cells. In particular, changes in Nf-κB signaling pathway, activity of nitric oxide synthases (NOS), metalloproteinases (MMPs), and membrane adhesion proteins were investigated. Read More
Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by leucocytes infiltration, demyelination, axonal degeneration and neuronal death. Although the etiology of MS is still unkwon, inflammation and autoimmunity are considered to be key players of the disease. Nervous System: The severe alterations affecting the nervous system contribute to the motor and cognitive disabilities and are in large part dependent on severe inflammatory processes active in both central nervous system and immune system. Read More
Background: The Placebo is defined as an inert substance with a potent therapeutic effect. Its effect is attributed to its psychological and neurobiological effect. Its use in Psychiatric drug practice, drug trials and clinical practice is common, especially in India. Read More
Background: The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptors in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Nicotinic Receptors: They are involved in the regulation of several activities ranging from excitatory neurotransmission, the modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death. Read More
Background: The use of central nervous system (CNS) acting drugs in the management of neuro degenerative and psychiatric problems cannot be overemphasized. Therefore, the chemical structure of piroxicam can be modified to yield new CNS stimulants and depressants that can be of great benefit to man and animals.
Methodology: Acetylcholine has Methyl - Oxygen-Oxygen (M-O-O) and Nitrogen (N) functional groups which are structurally related to Sulphur-Oxygen-Oxygen (S-O-O) and Nitrogen (N) of piroxicam that are either methylated or hydrogenated. Read More
Background: Medicinal chemistry methodologies are presently used to develop multifunctional molecules which simultaneously reduce oxidative stress, excitotoxicity, metal dyshomeostasis, and neuroinflammation that characterize neuropathological conditions, such as Alzheimer's Disease.
Results: Memantine (MEM) derivatives 1-6 were designed and synthesized as novel multifunctional entities with antioxidant and neuroprotective capabilities to manage neurodegenerative diseases, such as Alzheimer's Disease. In vitro neuroprotective studies were performed by using astroglial GL15 cell line to assess antioxidant capability of MEM derivatives 1-6. Read More
The nervous system is responsible for the communication between the organism and its environment. This task is possible by the presence of the myelin sheath, which is a double membrane formed by about 75% lipids and 25% proteins. The sulfatide represents one of the main lipids of the myelin band; its degradation is catabolized by the enzyme Arylsulfatase A (ARSA), to generated galactosylceramide. Read More
Adequate function of the nervous system depends on the balance of glia-neuron complex interactions. Astrocytes, in particular, are key elements in this process due to the significant participation of these cells in essential properties of the nervous system such as neuroinflammation, regulation of neurotransmitters, release of gliotransmitters and control of synaptic plasticity, among others. Astrocytes express the receptor for advanced glycation end products (RAGE) which is very important in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. Read More
Following in-depth analysis and examination, jellyfish toxins have been found to consist of a mixture of proteins, carbohydrates, and other non-proteinaceous components. What remains to be clarified is the specific chemical nature of jellyfish toxins due to their heat lability. This paper reviews current knowledge of the toxic properties of the most common Mediterranean scyphozoans (A. Read More
Background: It is reported that endogenous cannabinoids can cause vasodilation and bradycardia. They have anti-inflammatory effect and protect endothelial cells from injury, therefore they have potential application prospect in the prevention of cardio-cerebrovascular diseases. However, the mechanisms of the neuroprotection mediated by cannabinoid 1 receptors (CB1Rs) have not been uncovered in detail. Read More
Background: Schiff bases have a broad spectrum of biological activities like antiinflammatory, analgesic, antimicrobial, anticonvulsant, antitubercular, anticancer, antioxidant, anthelmintic and so forth. Thus, after a thorough perusal of literature, it was decided to conjugate benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine with aromatic and heteroaromatic aldehydes to get a series of Schiff bases.
Objective: Synthesis, characterization, in-silico toxicity profiling and anticonvulsant activity of the Schiff bases of Benzothiazol-2-ylamine and Thiazolo [5, 4-b] pyridin-2-ylamine. Read More
Background: Diabetes mellitus is a chronic degenerative disease responsible for hyperglycemic episodes through insulin secretion deficiency or cellular resistance. Clinical diagnosis in diabetic patients established that this disease affects the CNS, damaging the brain and impairing cognition, and thus establishing a clinical diabetic condition named diabetic encephalopathy. Despite the physiological mechanisms responsible for the development diabetic encephalopathy are still unclear, an excessive formation of reactive oxygen species, an alteration of acetylcholinesterase activity, and a reduction of growth factor levels, may be related with the pathogenesis of this condition. Read More
Anticonvulsant refers to a group of pharmaceuticals used in the treatment of epileptic seizures. The use of current antiepileptic drugs has been questioned due to the non-selectivity of the drugs and the undesirable side effects produced by them. This led to the search for antiepileptic compounds with more selectivity and lower toxicity. Read More
Background: Epilepsy is a neurological disorder, characterized by seizures accompanied by loss or disturbance of consciousness affecting various physical and mental functions. Current anticonvulsant drugs are effective in controlling seizures in about 70% of cases, but their use is often limited by side effects like ataxia, megaloblastic anemia, hepatic failure. In search for a novel anticovulsant drug with better efficacy and lower toxicity, a series of novel pyrimidine based semicarbazone were designed and evaluated for antiepileptic activity. Read More
Chronic pain represents a research field on great clinical relevance and social impactful. It is associated to a variety of pathological events causing un altered excitability of peripheral nerves derived by tissue damage depending on physical, biological and chemical injury. In the last years much attention has been paid in the identification of novel molecules involved in mediating pain sensation useful as therapeutic tools for the development of new analgesic drugs. Read More
Background And Objective: Bacterial meningitis is a serious disease with high rate of mortality and morbidity in children. Invasion of pathogens causes brain and meningeal inflammation, which leads to release of biomarkers into cerebrospinal fluid (CSF). Identification of these biomarkers can help the physicians to differentiation between bacterial and aseptic meningitis. Read More
Background: There is still limited knowledge regarding the role of impaired brain glucose metabolism in the generation of aggression during diabetes. Additionally, there are rapidly replicating piece of evidence suggesting that topiramate may exert significant mood stabilizing effect. In this respect, we aimed to evaluate the neurometabolic correlates of the therapeutic effect of topiramate in a patient with diabetes and Intermittent explosive disorder (IED). Read More
Neuromyelitis optica (NMO) and multiple sclerosis (MS) have been reported in different populations. NMO is more frequent in non-Caucasians, and clinical phenotype differences between populations are likely influenced by genetic susceptibility. In Brazil, it has been reported that NMO patients have a mainly European ancestry background. Read More
Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative demyelinating disease of the central nervous system (CNS). Unfortunately, MS cause important disability in young adults and its prevalence is increasing. While the etiology of MS etiology is not completely understood, it seems to be a multifactorial entity that is influenced by both genetic and epigenetic modifications. Read More
Background: Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important.
Method: Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Read More
Marine organisms are the excellent sources for biologically active compounds. Cnidarian venoms are potentially valuable materials used for biomedical research and drug development. The present work was carried out to analyse haemolytic, analgesic and CNS depressant activity of sea anemone Heteractis aurora. Read More
Thiazolidines are multifaceted molecules and exhibit varied types of biological activities, and also showed anticonvulsants and antidepressants activity. It is the diversified class of heterocyclic compounds. Thiazolidinediones (TZD) has been shown beneficial action in various CNS diseases. Read More
Background: Degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is mainly catalysed by GABA aminotransferase (GABA-AT), excessive activity of which leads to convulsions. Inhibition of GABA-AT increases the concentration of GABA and can terminate the convulsions. Several studies have revealed that GABA analogues could be the outstanding scaffolds for the design of potent inhibitors of GABA-AT. Read More
Background: A quantitative structure-activity relationship (QSAR) study of novel Acetamide derivatives as specific Mono amino oxidase (MAO) A inhibitory agents was performed with 28 compounds to derive QSAR models for better activity and lesser side effects.
Methods: Various thermodynamic, electronic and steric parameters were calculated using Chem 3D package of molecular modeling software Chemoffice 7.0. Read More
Chronic demyelinating diseases of the central nervous system (CNS) are autoimmune conditions that, although rarely fatal, may lead to severe disability. Among these diseases, multiple sclerosis (MS) and neuromyelitis optica (NMO) are particularly important and subject of worldwide research. MS and NMO are chronic types of CNS disease, with recurrent episodes of demyelination. Read More
Medulloblastoma (MB) treatment is continuously evolving. Better treatment approaches, focused on particular molecular pathways involved in MB development and progression support new treatment strategies. This article explores the antiproliferative, proapoptotic and radiosensitizing effects of Methoxyamine (MX), a base excision repair (BER) inhibitor that has shown anticancer potential by sensitizing tumor cells to ionizing radiation and chemotherapy. Read More
Background: Smoking is the world's leading cause of preventable death among populations. Cigarette smoking increases the risk of numerous health problems, including heart diseases, stroke, atherosclerosis and many types of cancer, including lung, stomach and bladder cancers.
Outcomes: Many individuals find it difficult to stop smoking because of the addictive effects of nicotine and the presence of several monoamine oxidase (MAO) inhibitors in the tobacco smoke extract. Read More
Background: Hydrazone core is a versatile structural linker for the development of various classes of antiepileptic agents. The aim of this study was to investigate the anticonvulsant activity of thiophene based hydrazones according to the antiepileptic drug development program protocol.
Methods: The maximal electroshock-induced seizure and 6 Hz "Psychomotor" seizure test models in mice were performed. Read More
Alzheimer's disease (AD), the most common neurodegenerative disorder and demands to find a way for prevention and delayed onset. The development of therapeutics for AD is based on the amyloid cascade hypothesis (vaccines, β- and γ-Secretase inhibitors), or targeting tau and neurofibrillary tangle formation, neuroinflammation, etc. Cholinesterase, BACE-1, amyloid-β 1-42, γ and β-Secretase, Phosphodiesterase type IV (PDE4) inhibitors are the reported treatment strategies. Read More
Introduction: Chalcones are one of the major classes of naturally occurring compounds and have a vast significance in medicinal chemistry, presenting with a wide scope of pharmacological actions.
Discussion: The present review focused our attention onto the monoamine oxidase inhibitory activity of natural and synthetic chalcones. The review also emphasises the structure-activity relationship studies and molecular recognition of chalcones towards MAO-A and B inhibition. Read More