2024/12/11 by Jonas M. A. Schlicht, Jonas Manfred Albert Schlicht, Undine Ahlrep +4
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Neuroscience · #Mast cells and histamine #Neurotransmitter Receptor Influence on Behavior #Receptor Mechanisms and Signaling
paper · pdf · doi:10.1007/s00210-024-03683-7
crossref issued 2024/12/11 · crossref published 2024/12/11 · crossref published-online 2024/12/11 · openalex publication_date 2024/12/11 · crossref created 2024/12/11 · openalex created_date 2024/12/12 · crossref deposited 2025/05/30 · crossref published-print 2025/06/01 · crossref indexed 2026/07/30 · openalex updated_date 2026/07/31
Abstract Clozapine is an atypical antipsychotic (neuroleptic) drug. Clozapine binds to H 2 -histamine receptors in vitro. We wanted to test the hypothesis that clozapine might be a functional antagonist at human cardiac H 2 -histamine receptors. To that end, we studied isolated electrically stimulated left atrial preparations and spontaneously beating right atrial preparations from transgenic mice with cardiomyocyte-specific overexpression of the human H 2 -histamine receptor (H 2 -TG). For comparison, we used wild-type littermate mice (WT). Finally, we measured isometric force of contraction in isolated electrically stimulated muscle strips from the human right atrium (HAP) obtained from patients during bypass surgery. After pre-stimulation with histamine, clozapine (up to 10 µM) concentration and time dependently decreased beating rate in right atrial preparations from H 2 -TG. Clozapine concentration dependently 1, 3, and 10 µM decreased histamine-stimulated force of contraction in HAP. Clozapine (10 µM) decreased also the isoprenaline-stimulated force of contraction in HAP. In summary, clozapine can antagonize the function of H 2 -histamine and β-receptors in the human heart.