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Antidepressant Drugs: MAOIs and Other Agents01:23

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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...
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Antidepressant drugs are a class of medications primarily used for treating various mood disorders, including major depression, anxiety disorders, and other related conditions. These medicines work by modulating the neurotransmitter balance within the brain, alleviating depressive symptoms. Antidepressants can be broadly categorized into several groups according to their mechanism of action and chemical structure: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine...
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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Repurposing antidepressants for anticancer drug discovery.

Yihui Song1, Xiaoke Yang2, Bin Yu1

  • 1School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100000, China.

Drug Discovery Today
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Summary

Repurposing antidepressants shows promise for cancer treatment. Tranylcypromine (TCP)-based inhibitors targeting histone lysine specific demethylase 1 (LSD1) are being explored for their anticancer effects.

Keywords:
Anticancer drug discoveryAntidepressantsDrug repurposing

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Area of Science:

  • Oncology
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Drug repurposing offers a viable strategy for discovering novel cancer therapies by utilizing existing medications.
  • Several approved antidepressants are under investigation for their potential in cancer treatment, demonstrating a shift in therapeutic applications.

Purpose of the Study:

  • To review the anticancer mechanisms of antidepressants.
  • To discuss the challenges and future directions in repurposing antidepressants for cancer drug discovery.
  • To provide an overview of current antidepressant cancer therapies.

Main Methods:

  • Literature review of scientific studies and clinical trials on antidepressant repurposing for cancer.
  • Analysis of medicinal chemistry efforts, particularly focusing on tranylcypromine (TCP) derivatives.
  • Examination of histone lysine specific demethylase 1 (LSD1) inhibition as a therapeutic target.

Main Results:

  • Three antidepressants have progressed to clinical trials for cancer therapy.
  • Tranylcypromine (TCP)-based compounds targeting LSD1 have shown significant therapeutic promise in preclinical and clinical settings.
  • Antidepressants exhibit diverse anticancer mechanisms of action.

Conclusions:

  • Repurposing antidepressants is a promising strategy for novel cancer drug discovery.
  • Further research into TCP-based LSD1 inhibitors could lead to effective cancer treatments.
  • Understanding the anticancer mechanisms of antidepressants is crucial for their successful clinical application.