Modulation of haloperidol induced electrophysiological alterations on cardiac action potential by various risk factors and gender difference |
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Authors: | KG Raghu Richa Singh A Prathapan Govind Kumar Yadav |
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Institution: | aPharmacology Division, Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh (UP) 226001, India;bBiochemistry and Cell Culture Laboratory, Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala 695019, India |
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Abstract: | Haloperidol (HPL), well known antipsychotic drug can induce a marked QT prolongation and polymorphic arrhythmias. In this study we evaluated the influence of various induced risk factors such as electrolyte imbalance (hypokalemia and hypomagnesemia), gender difference, low pacing frequency, ischemia reperfusion insult on electrophysiological effect by haloperidol on electrically driven action potentials recorded from guinea pig papillary muscle. The doses of HPL ranging from 1 to 16 μM were used in this investigation. Action potentials (APs) were elicited electrically and recorded by classical microelectrode technique. HPL caused dose dependent prolongation of APD90 the final stage of repolarization, increased triangulation, and led into dispersion of action potential, conduction delay and conduction block. Magnitude of the effect of haloperidol was amplified significantly by most of the risk factors. Among the various risk factors, electrolyte imbalance (hypokalemia, hypomagnesemia) caused more amplification of HPL effect. Most of the risk factors amplified prolongation of APD90 by HPL. This effect is mainly due to the influence of these electrolytes and sex hormone on various ion channels involved in the repolarization phase of cardiac AP. This is the first report which provides an experimental evidence of amplification of electrophysiological effects of HPL in the presence of various risk factors. |
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Keywords: | Haloperidol Action potential Papillary muscle Risk factors Hypokalemia Hypomagnesemia |
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