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Related Concept Videos

Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders01:27

Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders

Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within the...
Antidepressant Drugs: MAOIs and Other Agents01:23

Antidepressant Drugs: MAOIs and Other Agents

Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Drug Therapy01:28

Drug Therapy

The advent of drug therapy has profoundly shaped modern mental health care, providing targeted treatments for a range of psychological disorders. Psychotherapeutic drugs, classified into antianxiety, antidepressant, and antipsychotic medications, address symptoms across anxiety disorders, mood disorders, and schizophrenia. While these medications have transformed patient outcomes, they require careful management due to their potential side effects and limitations.
Antianxiety Medications
Psychosis and Antipsychotic Drugs: Overview01:28

Psychosis and Antipsychotic Drugs: Overview

The term "psychosis" refers to a spectrum of mental disorders characterized by abnormal thoughts, perceptions, and behaviors. It can manifest as mood disorders, dementia, delirium with psychotic features, substance-induced psychosis with psychotic features, brief psychotic disorder, delusional disorder, schizoaffective disorder, and schizophrenia. Among all these disorders, schizophrenia is the most common psychotic disorder, affecting 1% of the worldwide population. Psychotic symptoms in all...

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Related Experiment Video

Updated: Jun 25, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
08:15

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

Published on: June 6, 2025

Desloratadine Rescues Schizophrenia-like Phenotypes by Inhibiting the Pathogenic 5-HT2AR-PI3K/AKT/mTOR Signaling

Yuhan Yao1, Weiliang Zhao1, Junyang Chen1

  • 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, People's Republic of China.

Molecular Neurobiology
|June 24, 2026
PubMed
Summary

The antihistamine desloratadine ameliorates schizophrenia-like behaviors in mice by targeting the 5-HT2A receptor (5-HT2AR) and the PI3K/AKT/mTOR pathway. This study supports desloratadine repurposing for schizophrenia treatment.

Keywords:
5-HT2ARDesloratadinePI3K/AKT/mTOR pathwaySchizophreniaSingle-nucleus RNA sequencing

Related Experiment Videos

Last Updated: Jun 25, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
08:15

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

Published on: June 6, 2025

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Schizophrenia (SCZ) treatment is limited, despite 5-HT2A receptor (5-HT2AR) being a validated target.
  • Repurposing existing drugs for SCZ, particularly those targeting 5-HT2AR, is underexplored.

Purpose of the Study:

  • To investigate the therapeutic potential of desloratadine (DLT), an antihistamine, for SCZ-like behaviors.
  • To elucidate the molecular mechanisms underlying DLT's efficacy, focusing on 5-HT2AR and downstream signaling pathways.

Main Methods:

  • Utilized an MK-801-induced male mouse model to assess SCZ-like behavioral deficits.
  • Performed single-nucleus RNA sequencing (snRNA-seq) to analyze 5-HT2AR expression in the medial prefrontal cortex (mPFC).
  • Integrated transcriptomic and biochemical analyses to identify downstream signaling pathways, including PI3K/AKT/mTOR.

Main Results:

  • Desloratadine (DLT) significantly ameliorated SCZ-like behavioral deficits in the mouse model.
  • DLT reversed the upregulation of 5-HT2AR in mPFC neurons, establishing a causal link to pathology.
  • The 5-HT2AR-PI3K/AKT/mTOR pathway was identified as a key mediator of neuroinflammation, apoptosis, and synaptic plasticity deficits, all reversed by DLT.

Conclusions:

  • Desloratadine (DLT) demonstrates therapeutic potential for schizophrenia by targeting the 5-HT2A receptor (5-HT2AR) and inhibiting the PI3K/AKT/mTOR pathway.
  • This study validates the 5-HT2AR-PI3K/AKT/mTOR axis as a druggable target for schizophrenia.
  • Repurposing desloratadine for schizophrenia is a promising therapeutic strategy.