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Title: | Modulation of the negative inotropic effect of haloperidol by drugs with positive inotropic effects in isolated rabbit heart | Authors: | Hatip-Al-Khatib, Izzettin Bolukbaşi-Hatip, F. |
Keywords: | Calcium Haloperidol Isolated heart Negative inotropism 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester calcium ion digoxin dobutamine dopamine haloperidol noradrenalin calcium calcium channel stimulating agent cardiotonic agent neuroleptic agent animal tissue apparatus article calcium transport concentration response controlled study drug effect heart left ventricle pressure heart muscle cell heart muscle contractility inotropism isolated heart male nonhuman priority journal rabbit analysis of variance animal chemical phenomena dose response heart contraction heart left ventricle function heart ventricle pressure in vitro study Analysis of Variance Animal Antipsychotic Agents, Butyrophenone Bay-K-8644 Calcium Channel Agonists Cardiotonic Agents Depression, Chemical Digoxin Dobutamine Dopamine Dose-Response Relationship, Drug In Vitro Male Myocardial Contraction Norepinephrine Rabbits Ventricular Function, Left Ventricular Pressure 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester Animals Antipsychotic Agents |
Abstract: | Haloperidol is a typical antipsychotic drug with inhibitory effects on dopamine and calcium homeostasis. In this study, the effect of haloperidol on the inotropism of rabbits' isolated heart was investigated by measuring the isovolumetric left ventricular pressure using a balloon in a modified Langendorff perfusion apparatus. Haloperidol at 0.01-0.3 µmol/l induced a negative inotropic effect (Emax = 77.95 ± 0.19; EC50 = 0.043 ± 0.002 µmol/l). The effect of haloperidol was decreased by Ca2+ (Emax = 42.93 ± 3.22; EC50 = 0.37 ± 0.07 µmol/l; pD'2 = 7.01 ± 0.16), Bay K 8644 (Emax = 30.75 ± 1.33; EC50 = 10.43 ± 1.5 µmol/l, pD'2 = 7.13 ± 0.12), and digoxin (Emax = 42.03 ± 3.72, EC50 = 0.32 ± 0.05 µmol/l, pD'2 = 6.81 ± 0.14). The effect of haloperidol was also reduced by norepinephrine (Emax = 37.16 ± 1.84; EC50 = 1.73 ± 0.24 µmol/l, pD'2 = 6.97 ± 0.08) and dopamine (Emax = 35.68 ± 2.78; EC50 = 0.69 ± 0.01 µmol/l, pD'2 = 7.48 ± 0.15). However, the effect of haloperidol was nonsignificantly reduced by dobutamine (Emax = 58.89 ± 5.18; EC50 = 0.15 ± 0.06 µmol/l, pD'2 = 5.88 ± 0.47). These results show that the drugs that increase the influx of Ca2+ into the cardiomyocyte decrease the negative inotropic effect of haloperidol, suggesting that the effect of haloperidol could be mediated via mechanisms involving actions on Ca2+ entry into the cardiomyocyte. Haloperidol should be used carefully when prescribed for patients with cardiovascular disorders. Copyright © 2002 S. Karger AG, Basel. | URI: | https://hdl.handle.net/11499/5365 https://doi.org/10.1159/000063249 |
ISSN: | 0031-7012 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection Tıp Fakültesi Koleksiyonu WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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