Modulation of haloperidol induced electrophysiological alterations on cardiac action potential by various risk factors and gender difference.
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 microM were used in this investigation. Action potentials (APs) were elicited electrically and recorded by classical microelectrode technique. HPL caused dose dependent prolongation of APD(90) 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 APD(90) 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.
Pharmacology Division, Central Drug Research Institute, Lucknow, Uttar Pradesh 226001, India. raghukgopal@rediffmail.com
K G
KG
Raghu
Richa
R
Singh
A
A
Prathapan
Govind Kumar
GK
Yadav
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006168:Guinea Pigs; D006220:Haloperidol / Q000633:toxicity*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects; D012307:Risk Factors; D012737:Sex Factors
D014150:Antipsychotic Agents; D004573:Electrolytes; D012739:Gonadal Steroid Hormones; D007473:Ion Channels; D006220:Haloperidol