ArticleThe Journal of biological chemistry2011
Clemastine potentiates the human P2X7 receptor by sensitizing it to lower ATP concentrations.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis.The Journal of clinical investigation · 2025Trial
- Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Effects on mouse melanoma and immune cells of P2X7 receptor positive allosterism by clemastine.Purinergic signalling · 2026Article
- Immune-adaptive pathogen variation reveals targetable mediators of gram-positive bacterial killing in macrophages.Science advances · 2026Article
- Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment.FEMS microbiology reviews · 2024Review
- Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.Purinergic signalling · 2024Review
- Article
- Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages.Purinergic signalling · 2024Article
- Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.Frontiers in pharmacology · 2024Review
- Animal Models for the Investigation of P2X7 Receptors.International journal of molecular sciences · 2023Review
- Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022Review
- Histamine and Microglia.Current topics in behavioral neurosciences · 2022Review
- Agonists, Antagonists, and Modulators of P2X7 Receptors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- P2X7 is a cytotoxic receptor….maybe not: implications for cancer.Purinergic signalling · 2021Review
- Insights into the Structure-Activity Relationship of Glycosides as Positive Allosteric Modulators Acting on P2X7 Receptors.Molecular pharmacology · 2021Article
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- Abacavir Increases Purinergic P2X7 Receptor Activation by ATP: Does a Pro-inflammatory Synergism Underlie Its Cardiovascular Toxicity?Frontiers in pharmacology · 2021Article
- Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor.International journal of molecular sciences · 2020Review
- P2X7 Receptors as a Therapeutic Target in Cerebrovascular Diseases.Frontiers in molecular neuroscience · 2020Article
- To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors?Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2X7 receptors have emerged as potential drug targets for the treatment of medical conditions such as e.g. rheumatoid arthritis and neuropathic pain. To assess the impact of pharmaceuticals on P2X7, we screened a compound library comprising approved or clinically tested drugs and identified several compounds that augment the ATP-triggered P2X7 activity in a stably transfected HEK293 cell line. Of these, clemastine markedly sensitized Ca(2+) entry through P2X7 to lower ATP concentrations. Extracellularly but not intracellularly applied clemastine rapidly and reversibly augmented P2X7-mediated whole-cell currents evoked by non-saturating ATP concentrations. Clemastine also accelerated the ATP-induced pore formation and Yo-Pro-1 uptake, increased the fractional NMDG(+) permeability, and stabilized the open channel conformation of P2X7. Thus, clemastine is an extracellularly binding allosteric modulator of P2X7 that sensitizes P2X7 to lower ATP concentrations and facilitates its pore dilation. The activity of clemastine on native P2X7 receptors, Ca(2+) entry, and whole-cell currents was confirmed in human monocyte-derived macrophages. Similar effects were observed in murine bone marrow-derived macrophages. Consistent with the data on recombinant P2X7, clemastine augmented the ATP-induced cation entry and Yo-Pro-1 uptake. In accordance with the observation that P2X7 controls the cytokine release from LPS-primed macrophages, we found that clemastine augmented the IL-1β release from LPS-primed human macrophages. Collectively, these data point to a sensitization of the recombinantly or natively expressed human P2X7 receptor toward its physiological activator, ATP, possibly leading to a modulation of macrophage-dependent immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.