2. Academic Validation
  3. The antipsychotic drug pimozide inhibits IgE-mediated mast cell degranulation and migration

The antipsychotic drug pimozide inhibits IgE-mediated mast cell degranulation and migration

  • Int Immunopharmacol. 2020 Jul;84:106500. doi: 10.1016/j.intimp.2020.106500.
Yi-Bo Hou 1,  Li-Na Zhang 1,  Hui-Na Wang 1,  Zhen-Fu Zhao 2,  Yue-Tong Sun 1,  Kunmei Ji 3,  Jia-Jie Chen 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China. Electronic address: zhb@szu.edu.cn.
  • 3 Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China. Electronic address: jkm@szu.edu.cn.
  • 4 Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China. Electronic address: chenjj@szu.edu.cn.
PMID: 32311669 DOI: 10.1016/j.intimp.2020.106500
Abstract

Background: Mast cells (MCs) mediate a key role in allergic diseases. Detailed studies of how the neuroleptic drug pimozide affects MC activity are lacking. The aim of this study was to investigate pimozide inhibition of immunoglobulin E (IgE)-mediated MC activation and MC-mediated allergic responses.

Method: MCs were stimulated with anti-dinitrophenyl (DNP) IgE Antibodies and DNP-horse serum albumin (HSA) antigen (Ag), and anti-allergic pimozide effects were detected by measuring β-hexosaminidase levels. Morphological changes were observed histologically. In vivo pimozide effects were assessed in passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-sensitized active systemic anaphylaxis mouse (ASA) model experiments. Levels of phosphorylated (p-) Syk (spleen tyrosine kinase) and MAPKs (mitogen-activated protein kinases) were detected in western blots.

Results: We found that pimozide inhibited MC degranulation, reduced MC release of β-hexosaminidase dose-dependently in activated RBL-2H3 (IC50: 13.52 μM) and bone marrow derived MC (BMMC) (IC50: 42.42 μM), and reduced MC morphological changes. The IgE/Ag-induced migration effect was suppressed by pimozide treatment dose-dependently. Pimozide down-regulated IgE/Ag-induced phosphorylation of Syk and MAPKs in activated MCs. Moreover, pimozide attenuated allergic reactions in PCA and ASA model mice, and decreased MC populations among splenic cells.

Conclusions: The antipsychotic drug pimozide can suppress IgE-mediated MC activation in vitro and in vivo and should be considered for repurposing to suppress MC-mediated diseases.

Keywords

Cell degranulation; Drug repurposing; Mast cells; Pimozide.

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