Abstract
Aim:
To study the effects of haloperidol on sodium currents (INa) in guinea pig ventricular myocytes.
Method:
Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on INa in individual ventricular myocytes.
Results:
Haloperidol (0.1-3 μmol/L) inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 7μmol/L. The inhibition rate of haloperidol (0.3 μmol/L) on INa was 22.14% ± 0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactivation of INa by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%±1.4% (n=6); however, haloperidol at 0.03 μmol/L enhanced INa conductance. The midpoints for the activation and inactivation of INa were shifted by 1.38 and 5.69 mV, respectively, at this concentration of haloperidol.
Conclusion:
Haloperidol displayed a biphasic effect on INa in guinea pig cardiac myocytes. High concentrations of haloperidol inhibited INa, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.
Similar content being viewed by others
Article PDF
References
Si TM, Shu L, Yu X, Ma C, Wang GH, Bai PS, et al. Antipsychotic drug patterns of schizophrenia in China: a cross-sectioned study. Chin J Psychiatry, 2004; 37: 152–5.
Gury C, Canceil O, Iaria P . Antipsychotic drugs and cardiovascular safety: current studies of prolonged Q-T interval and risk of ventricular arrhythmia. Encephale, 2000; 26: 62–72.
Zhou GB . Observation of electrocardiogram on patients taking haloperidol. Heilongjiang Med J, 2002; 25: 95.
Wu FM, Zhang JF . The effects of antipsychotic drugs on ECG of children. Chin J Psychiatry, 1994; 27: 16.
Gardner DM, Baldessarini RJ, Waraich P . Modern antipsychotic drugs: a critical overview. CMAJ, 2005; 172: 1703–11.
Ogata N, Narahashi T . Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol, 1989; 97: 905–13.
Mortl D, Agneter E, Krivanek P, Koppatz K, Todt H . Dual rate-dependent cardiac electrophysiologic effects of haloperidol: slowing of intraventricular conduction and lengthening of repolarization. J Cardiovasc Pharmacol, 2003; 41: 870–9.
Li GR, Baumgarten CM . Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias. Am J Physiol Heart Circ Physiol, 2001; 280: 272–9.
Bean B P, Cohen CJ, Tsien RW . Lidocaine block of cardiac sodium channels. J Gen Physiol, 1983; 81: 613–42.
Cambell TJ . Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea pig ventricle and provide a theoretical basis for their subclassification. Cardiovasc Res, 1983; 17: 344–52.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cheng, Lf., Yan, D., Turdi, S. et al. Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes. Acta Pharmacol Sin 28, 783–788 (2007). https://doi.org/10.1111/j.1745-7254.2007.00575.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00575.x