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Clozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK-STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking.
CNS Neurosci Ther
January 2025
Computational Biology Center, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, China.
Background: Clozapine exhibits significant therapeutic efficacy in schizophrenia, especially treatment-resistant schizophrenia. However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore this mechanism based on network pharmacology and molecular docking.
Method: Six and two databases were used to identify targets associated with clozapine and agranulocytosis, respectively.
Network pharmacology and molecular docking to explore mechanisms of clozapine-induced cardiac arrest.
J Psychiatry Neurosci
January 2025
From the Computational Biology Centre and the Laboratory of Psychiatric-Neuroimaging-Genetic and Comorbidity, Tianjin Anding Hospital, Tianjin Mental Health Centre of Tianjin Medical University, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China.
Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.
Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.
Lessons learnt in the end-of-life management of a hospice inpatient with advanced oropharyngeal cancer established on clozapine for treatment-resistant schizophrenia.
BMJ Case Rep
December 2024
Palliative Medicine, Aneurin Bevan University Health Board, Newport, UK.
Article Synopsis
- Clozapine is a critical medication for treatment-resistant schizophrenia but must be used carefully due to its narrow therapeutic range and potential for serious side effects.
- Patients with mental health issues often have heightened risks for head and neck cancers from lifestyle factors and may struggle to access adequate healthcare.
- Effective management requires careful planning, ongoing monitoring, and collaboration among healthcare professionals to balance the risks of clozapine toxicity and underdosing in patients with declining health.
Alert prescribing of clozapine: a comparison of five drug-drug interaction sources.
Ther Adv Drug Saf
December 2024
University Psychiatric Center KU Leuven, Z.org KU Leuven, Kortenberg, Belgium.
Article Synopsis
- Clozapine is an antipsychotic for schizophrenia that has serious side effects, making drug-drug interaction (DDI) databases important for clinician reference.
- This study analyzed DDI information from five different databases to assess their agreement on potential interactions with clozapine.
- Out of 183 potential DDIs identified, only 47.5% showed consensus across the databases, highlighting significant discrepancies that could affect patient safety and prescribing practices.
Glial cells undergo rapid changes following acute chemogenetic manipulation of cortical layer 5 projection neurons.
Commun Biol
October 2024
Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, OX1 3PT, United Kingdom.
Article Synopsis
- Bidirectional communication between neurons and glial cells is essential for proper brain function, but the effects of sudden changes in neuronal activity on these interactions are not well understood.
- In this study, researchers used a technique called DREADD to manipulate specific neuron populations in mouse brains, discovering that activating neurons leads to reduced synaptic density and increased glial cell reactivity, while silencing them has the opposite effect.
- The findings highlight rapid and dynamic interactions between neurons and glial cells that are influenced by neuronal activity, contributing to our understanding of brain function and potential implications for neurological conditions.
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