Current Drug Targets - Volume 24, Issue 3, 2023

Background: Epilepsy is a neurological disease affected by an imbalance of inhibitory and excitatory signaling in the brain. Introduction: In this disease, the targets are active in pathophysiology and thus can be used as a focus for pharmacological treatment. Methods: Several studies demonstrated the antiepileptic effect of drugs acting on the following targets: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-gated calcium channel (Cav), Gamma aminobutyric acid transporter type 1 (GAT1), voltage-gated sodium channels (Nav), voltage-gated potassium channel of the Q subfamily (KCNQ) and Gamma aminobutyric acid type A (GABAA) receiver. Results: These studies highlight the importance of molecular docking. Conclusion: Quantitative Structure-Activity Relationship (QSAR) and computer aided drug design (CADD) in predicting of possible pharmacological activities of these targets.

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturallyderived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 μm using Ellman’s in vitro AChE assay method and show high BBB permeability in vitro. In addition, the in vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced β-amyloid (Aβ) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer’s disease.

Background: Constipation is one of the most frequent abnormalities of the gastrointestinal system that affects the patient’s quality of life. Constipation is more common in women and affects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipation research is not given much importance. Objective: This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 receptors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment. Methods: This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is considered in 40-90% of patients, which causes constipation as a side effect. On activation, 5HT-4 receptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liver. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the intestine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine. Conclusion: Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients’ needs in the future.

The mucosal surfaces are the key site of the entrance, protection, and stability of several pathogens. Considering that >90% of pathogens gain access to the body via mucosal sites, using mucosal vaccination to generate protective immunity at mucosal sites could overcome. Some of the micro and nano carrier-based nasal delivery systems produce cellular, humoral and mucosal immunity. The nasal route vaccination may protect multiple distant mucosal sites like-rectal, vaginal, oral, and pulmonary. Also, it is a convenient and cost-effective vaccination mode with improved patient compliance. Several nasal vaccine delivery systems are currently being supplied in the form of liposomes, micro/nano particulates, which have shown immunity in animal models. Especially particulate nanovaccine has a special character related to long-term immunogenicity and high efficiency. The significance and the ability of the nasal route vaccination programs are unexplained and complications; therefore, effective delivery strategies will promote the production of nasal vaccines. The present study focuses on vaccine delivery strategies and their effects on the immune system. Also, the study discusses the benefits of mucosal-associated immune response over the conventional delivery system for vaccine via the nasal route.

With a prevalence ranging from 16-21%, tinnitus is an irking neurological disorder, manifesting as the perception of a roar of cacophony without an external acoustic stimulus. Although tinnitus is a non-life-threatening symptom, tinnitus's negative repercussions, such as personality disturbances and social withdrawal, are daunting concerns despite a gamut of conventional and emerging treatment options. Tinnitus management is still a critical challenge that provides opportunities for clinicians, ENT (Ear/eye, nose and throat) physicians, and other specialists such as audiologists, psychiatrists, and psychologists. Among the new treatment modalities, Neuromonics tinnitus treatment (NTT) draws special attention in tinnitus management due to its mounting success rate. Nonetheless, unlike in developed countries like Australia, the United States, and the United Kingdom, the scanty awareness of NTT among Indian ENT specialists is a titanic setback for care providers. Because of this backdrop, this review emphasized the current perspectives on tinnitus management and the underlying principles and clinical efficacy of NTT. The challenges for tinnitus management can be met and reduced by suppressing tinnitus through motivation, counseling, cochlear implant, and psychotherapy.

Introduction: The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). Methods: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized. Results: Only the combined treatment with TH and GNPs promoted a reduction in proinflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. Conclusion: The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.