Effects of Haloperidol on Cardiac Histamine H2 Receptors and β-Adrenoceptors in Isolated Mouse and Human Atrial Preparations.

The antipsychotic drug haloperidol is found on the WHO list of essential drugs. In vitro, haloperidol demonstrates binding affinity for various receptors, including histamine H₂ receptors (H₂Rs). Several cardiac effects of haloperidol are known, but it remains unclear whether H₂Rs are involved. Here, the hypothesis was tested that haloperidol has the potential to act as either an agonist or an antagonist of human cardiac H₂Rs. The contractile effects of haloperidol were studied in isolated left and right atrial preparations from transgenic mice overexpressing human H₂Rs in the heart (H₂-TG), and compared to human atrial preparations from adult patients. Haloperidol reduced the histamine-stimulated force of contraction in the human atrial preparations as well as the histamine-stimulated force of contraction and beating rate in the left and right atrial preparations from the H₂-TG, respectively. Moreover, haloperidol reduced the isoprenaline-stimulated force of contraction in the human atrial preparations. In the wild-type mouse preparations, haloperidol only reduced the isoprenaline-stimulated beating rate in the right atria, but not the force in the left atria. Principally, haloperidol is capable of acting as an antagonist of both H₂Rs and β-adrenoceptors in the human heart. However, the effects are only relevant at very high doses of haloperidol, which are never or seldom achieved in practice.