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Psychosis: Goals of Pharmacotherapy01:26

Psychosis: Goals of Pharmacotherapy

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Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation.
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Related Experiment Video

Updated: Feb 28, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
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Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

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Clozapine Mitigates Lipopolysaccharide-Induced Cognitive Dysfunction by Modulating Cholinergic Function, Oxidative

Vasudevan Mani1, Mohammed A Almatrafi1

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.

Life (Basel, Switzerland)
|February 27, 2026
PubMed
Summary

Clozapine (CLZ) treatment improved cognitive function in a rat model of neurotoxicity. CLZ demonstrated neuroprotective effects by modulating key molecular pathways involved in cognition and cell survival.

Keywords:
apoptosisclozapinecognitive functionlipopolysaccharideneurodegenerationoxidative stress

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Clozapine (CLZ) is an atypical antipsychotic used for treatment-resistant schizophrenia.
  • Schizophrenia patients often experience persistent cognitive impairments.
  • Mechanisms of CLZ's cognitive and neuroprotective effects require further elucidation.

Purpose of the Study:

  • To investigate the neuroprotective effects of CLZ against lipopolysaccharide (LPS)-induced neurotoxicity in rats.
  • To explore how CLZ modulates cognitive function and related molecular pathways.

Main Methods:

  • Rats were administered LPS to induce neurotoxicity, followed by CLZ treatment.
  • Cognitive function was assessed using behavioral maze tests (EPM, NOR, Y-maze).
  • Molecular analyses included cholinergic function, neurodegeneration markers, oxidative stress, and apoptosis.

Main Results:

  • CLZ treatment significantly improved cognitive performance in behavioral tests.
  • CLZ enhanced acetylcholine (ACh) levels and upregulated the anti-apoptotic protein Bcl-2.
  • CLZ reduced neurotoxicity markers, including GSK-3β activity, lipid peroxidation (LPO), and pro-apoptotic proteins (Bax, c-Caspase-3), while restoring antioxidant defenses (catalase, GSH).

Conclusions:

  • CLZ exhibits neuroprotective effects in an LPS-induced rat model, enhancing cognition.
  • CLZ's benefits are mediated by modulating cholinergic transmission, oxidative stress, and apoptosis.
  • These findings support CLZ's potential for improving cognitive deficits in schizophrenia.