Current Psychopharmacology - Volume 13, Issue 1, 2025

Epilepsy is the second most typical chronic disorder, described by recurrent seizures and uncontrolled electrical signaling from neurons in the cerebral cortex. Stimulated astrocytes, along with microglia, promote cytokines that cause neuroinflammation, leading to a chain reaction of subsequent steps involving neurons as well as endothelial cells along the blood-brain barrier. Inflammation in the brain’s neural network can cause convulsions and epilepsy. The migration of albumin proteins and the infiltration of peripheral immune cells from the serum into the brain disrupt BBB, which, in turn, activates astrocytes and microglia, which stimulate pro-inflammatory mediators like cytokines, chemokines, and other inflammatory mediators. They increase the glutamate level and cause an influx of calcium ions, leading to the production of less GABA and a decrease in the influx of chloride ions. These events exacerbate the inflammatory process that leads to neuronal excitability and contribute further to the development of epilepsy. In this review, we discuss how astrocytes, microglia, and neurons stimulate cytokines, chemokines, and other inflammatory mediators that play an essential role in the development of epilepsy. This review also explore how the permeability of the blood-brain barrier promotes neuroinflammation and contributes to epileptogenesis. The purpose of this review is to present knowledge on neuroinflammation so that new antiepileptic drugs can be developed to prevent this disorder.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and motor dysfunction. The monoamine oxidase B (MAO-B) pathway plays a critical role in the pathogenesis of PD by contributing to neurodegeneration through oxidative stress. Precision medicine offers a transformative approach to PD treatment by leveraging genetic and molecular insights to tailor therapeutic strategies. This review explores the intersection of precision medicine and antipsychotic drugs in modulating the MAO-B pathway to mitigate PD symptoms. We discuss the biochemistry and function of MAO-B, its impact on disease progression, and the potential of genetic profiling to personalize treatment. Additionally, we examine the role of antipsychotic drugs, their mechanisms of action, and their interactions with the MAO-B pathway. The review highlights personalized approaches to MAO-B inhibition and the clinical evidence supporting these strategies. We address the challenges and limitations in implementing precision medicine, such as technical difficulties, drug interactions, and variability in patient responses. Finally, we explore future directions, including advances in precision medicine technologies and emerging therapies and their potential to enhance PD management. This review examines the indirect interaction between antipsychotics and the MAO-B pathway, highlighting how genetic variations and enzyme activity may influence drug efficacy, safety, and potential adverse effects, particularly when combined with MAO-B inhibitors in neuropsychiatric treatments.

Donanemab is the first antibody to target pyroglutamate-modified amyloid-beta in Alzheimer's disease selectively; thus, it represents a significant breakthrough in disease-modifying treatments. Importantly, its mechanism of action encourages adequate clearance of plaques and does not even worsen outcomes for early-stage patients, in contrast to previous treatments that did not promote clearing for plaques or even worsened the outcomes of early-stage patients. The integration of quantum computing in drug discovery holds tremendous transformations in terms of enhancing the therapeutic approach against Alzheimer's disease. Researchers can speed up discovering novel compounds, optimize treatment regimens, and personalize patient care according to individual neurobiological profiles by using quantum computing powers. The letter to the editor discusses the unique attributes of donanemab, its clinical superiority, and the related side effects, besides pushing for the promising future of integrating quantum computing into the paradigms of Alzheimer's treatment. Though promising, integrating quantum computing into medical practice is challenged by factors such as high computational costs, data privacy, and ethical considerations that must be taken within strict regulatory frameworks.

Alzheimer's disease is distinguished by gradual changes in behavior because of the aggregation of β-amyloid and τ protein that blocks the signal transduction pathway. It is one of the major problems in the current scenario. It mainly occurs after the age of 60 and eventually leads to memory loss. Nonetheless, medicinal plants have therapeutic potential to improve many diseases. Medicinal drugs with their phytoconstituents may offer therapeutic potential for improving the preventive treatment for Alzheimer's disease. Five synthetic drugs that have been approved by the FDA include Tacrine, Rivastigmine, Donepezil, Galantamine, and Memantine for the symptomatic treatment of Alzheimer's. In the search for effective anti-Alzheimer's drugs from a natural source, we discovered marine resources as the origin of the therapeutic and nutritional compound. The methodology involves conducting a comprehensive literature survey. The database search methodology used in this review was the use of keywords, which can be found in the article pertaining to Alzheimer’s disease. The significant articles focused on marine flora phytoconstituents, such as acetylcholinesterase or butyrylcholinesterase inhibitors, thus prompting a comprehensive review based on pertinent information. The review included descriptions of various studies, revealing that numerous compounds derived from marine sources have demonstrated promising efficacy in the treatment of Alzheimer's disease. Many compounds that originated from marine sources showed good efficacy in treating Alzheimer’s disease. Acetylcholinesterase or butyrylcholinesterase inhibition was the main pharmacological mechanism that was reported for most of the molecules, however, few articles having alternative anti Alzheimer’s mechanisms have also been reported. This article highlights marine compounds derived from marine sources like algae, fungi, and sponges, which can combat Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, effective treatments remain elusive, highlighting the need for innovative therapeutic approaches. This review article explores enzymatic targets and drug development strategies aimed at combating AD. Key enzymatic targets include beta-secretase (BACE1), gamma-secretase, and tau protein kinases, all of which play critical roles in the pathogenesis of AD. BACE1 and gamma-secretase are involved in the production of amyloid-beta (Aβ) peptides, whose aggregation forms the hallmark amyloid plaques in AD brains. Inhibitors targeting these enzymes aim to reduce Aβ production and accumulation. Tau protein kinases, such as glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinase 5 (CDK5), are implicated in tau hyperphosphorylation and subsequent neurofibrillary tangle formation. Modulating these kinases offers the potential for reducing tau pathology. The review further discusses various drug development strategies, including small-molecule inhibitors, monoclonal antibodies, and gene therapy. Small molecule inhibitors, such as BACE1 and gamma-secretase inhibitors, have shown promise in preclinical studies but face challenges related to specificity and side effects. Monoclonal antibodies targeting Aβ and tau provide an alternative approach, with several candidates currently undergoing clinical trials. Gene therapy represents a cutting-edge strategy aiming to correct or modulate disease-causing genetic mutations. In summary, targeting enzymatic pathways involved in AD pathogenesis offers a promising avenue for drug development. While significant challenges remain, ongoing research and clinical trials continue to advance our understanding and potential treatment options for this debilitating disease.

Neuroleptic drug therapy, used to manage psychotic disorders, often induces hormonal disruptions that can impact patient health and treatment outcomes. This review explores the relationship between neuroleptic medications and the endocrine system, highlighting current insights and clinical challenges. Antipsychotic drugs often elevate prolactin levels, leading to hyperprolactinemia, which manifests as galactorrhea, amenorrhea, and sexual dysfunction. These medications can also alter insulin and glucagon levels, contributing to metabolic syndromes, like type 2 diabetes and insulin resistance. Disruption of thyroid hormone homeostasis can result in hypothyroidism or hyperthyroidism, exacerbating psychiatric symptoms. Moreover, neuroleptic drugs affect growth hormone and adrenal function, potentially causing weight gain and adrenal insufficiency. Understanding these hormonal side effects is crucial for developing treatment plans that mitigate adverse effects while optimizing psychiatric care. Despite advances in psychopharmacology, challenges remain in predicting individual patient responses and managing long-term endocrine complications. Current research underscores the need for routine endocrine monitoring in patients on neuroleptic therapy and exploring adjunctive treatments to counteract these side effects. Future studies should focus on elucidating the molecular mechanisms underlying these hormonal disruptions and developing targeted interventions to improve patient outcomes. This review provides an overview of the hormonal side effects of neuroleptic drugs, emphasizing the importance of interdisciplinary approaches in addressing the needs of patients with psychotic disorders.

Despite the availability of numerous anti-hyperglycemic and psychoactive drugs, and diverse therapeutic modalities, prevention and cure of diabetes-associated mental health problems continue to be a major challenge for medical practitioners. Considerable efforts have been made in many research laboratories, including ours, to identify the bioactive of traditionally known medicinal or food plants to identify their bioactive that could be used for the treatment of diabetes and comorbidities in metabolic disorders. Andrographis paniculata (Burm. F.) Wall. Ex. Nees. has been used in Ayurvedic and other traditionally known healthcare systems of India and many other Asian countries. Due to its extremely bitter taste, it is often referred to as the “king of bitters” and commonly known as “Kalmegh”. Andrographolide is one such metabolite of Andrographis paniculata used in many Asiatic countries for the treatment of diverse age and lifestyle-associated chronic diseases now used for discovering and developing anti-diabetic and other drugs. Available data on andrographolide and Andrographis paniculata strongly recommend that they could be better therapeutic choices for the prevention of diabetes and associated mental health problems than metformin and other pharmacotherapeutics currently commercialized for such purposes. However, the question of whether andrographolide or extracts of the plant enriched in it could be better suited for such purposes remains open. Currently, available quantitative data on their anti-hyperglycemic effects and brain function-modulating effects useful for answering this question are discussed in this report in light of our current knowledge of the role of gut microbiota in regulating glucose homeostasis and mental health. Their potential uses for discovering and developing drugs or phytotherapeutics from them are also pointed out.