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Related Concept Videos

Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs01:25

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Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
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Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
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Upper Respiratory Drugs: First and Second-Generation Antihistamines01:15

Upper Respiratory Drugs: First and Second-Generation Antihistamines

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Antihistamines are a class of drugs widely used to alleviate the symptoms of allergies, such as sneezing, itching, and nasal congestion. They work by inhibiting the actions of histamine, which is released by immune cells in response to allergenic substances or tissue injuries.
Histamine binds to specific receptor sites, known as H1 receptors, on tissue cells, triggering inflammation and swelling. Antihistamines combat these effects by competing with histamine for these receptor sites. By...
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Cholinergic Antagonists: Therapeutic Uses01:26

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Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:    
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal...
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Antiasthma Drugs: Leukotriene Modifiers01:19

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Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
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Antiasthma Drugs: Muscarinic Receptor Antagonists01:20

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Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
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Repurposing Histaminergic Drugs in Multiple Sclerosis.

Susanna Amadio1, Federica Conte2, Giorgia Esposito1

  • 1IRCCS Santa Lucia Foundation, Preclinical Neuroscience, Via del Fosso di Fiorano 65, 00143 Rome, Italy.

International Journal of Molecular Sciences
|June 10, 2022
PubMed
Summary

Histamine signaling shows potential for treating multiple sclerosis by regulating myelin repair. Drug repurposing identified amodiaquine, rupatadine, and diphenhydramine as potential new therapies for this autoimmune disease.

Keywords:
H1 receptoramodiaquinediphenhydraminehistamine N-methyltransferasemultiple sclerosisnetwork medicinerupatadine

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Area of Science:

  • Neuroimmunology and Pharmacology
  • Biomedical Informatics and Drug Discovery

Background:

  • Multiple sclerosis (MS) is an autoimmune disease characterized by neuroinflammation, demyelination, and neurodegeneration in the central nervous system.
  • Histamine signaling plays a complex role in MS, influencing oligodendrocyte precursor differentiation and remyelination, with effects varying by receptor subtype and timing.
  • Current drug development for MS has yielded limited curative options, highlighting the need for alternative therapeutic strategies like drug repurposing.

Purpose of the Study:

  • To explore the potential of histamine-related molecules as therapeutic agents for multiple sclerosis.
  • To identify novel drug-disease associations for multiple sclerosis using a network-medicine-based approach.
  • To predict potential off-label uses of existing histaminergic drugs for treating multiple sclerosis.

Main Methods:

  • Utilized the SAveRUNNER algorithm, a network-medicine-based approach, to analyze the interplay between MS-associated genes and drug targets within the human interactome.
  • Quantified drug-disease associations within the human interactome.
  • Identified and predicted novel therapeutic applications for existing drugs.

Main Results:

  • Identified novel drug-disease associations involving histamine and multiple sclerosis.
  • Predicted the potential repurposing of histaminergic drugs, including amodiaquine, rupatadine, and diphenhydramine, for the treatment of multiple sclerosis.
  • Highlighted the complex role of histamine receptor subtypes in modulating disease processes.

Conclusions:

  • Selected histamine-related molecules may address the underlying causes of multiple sclerosis.
  • Drug repurposing of histaminergic agents presents a promising avenue for developing new therapeutic strategies for multiple sclerosis.
  • Further investigation into these identified drug-disease associations could accelerate the development of effective MS treatments.