Clozapine is a functional antagonist at cardiac human H 2 -histamine receptors.

Autor: Schlicht JMA; Institute for Pharmacology and Toxicology, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Magdeburger Straße 4, Halle (Saale), D-06097, Germany., Ahlrep U; Institute for Pharmacology and Toxicology, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Magdeburger Straße 4, Halle (Saale), D-06097, Germany., Hofmann B; Department of Cardiac Surgery, Mid-German Heart Center, University Hospital Halle, Ernst Grube Straße 40, Halle (Saale), D-06097, Germany., Kirchhefer U; Institute for Pharmacology and Toxicology, University Münster, Domagkstraße 12, Münster, D-48149, Germany., Neumann J; Institute for Pharmacology and Toxicology, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Magdeburger Straße 4, Halle (Saale), D-06097, Germany. joachim.neumann@medizin.uni-halle.de., Gergs U; Institute for Pharmacology and Toxicology, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Magdeburger Straße 4, Halle (Saale), D-06097, Germany.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Dec 11. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1007/s00210-024-03683-7
Abstrakt: 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.
Competing Interests: Declarations. Ethical approval: Animals: The investigation conformed to the Guide for the Care and Use of Laboratory Animals as published by the National Research Council (2011). The animals were handled and maintained according to the approved protocols of the Animal Welfare Committee of the University of Halle-Wittenberg, Halle, Germany. Humans: This study complies with the Declaration of Helsinki and has been approved by the local ethics committee. Consent to participate: Informed consent was obtained from all patients included in the study. Consent for publication: All authors declare that they have seen and approved the submitted version of this manuscript. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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