Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

To study the effects of haloperidol on sodium currents (I(Na)) in guinea pig ventricular myocytes.

Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on I(Na) in individual ventricular myocytes.

Haloperidol (0.1-3 micromol/L) inhibited I(Na) in a concentration-dependent manner with an IC50 of 0.253+/-0.015 micromol/L. The inhibition rate of haloperidol (0.3 micromol/L) on I(Na) was 22.14%+/-0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactivation of I(Na) 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 micromol/L enhanced I(Na) conductance. The midpoints for the activation and inactivation of I(Na) were shifted by 1.38 and 5.69 mV, respectively, at this concentration of haloperidol.

Haloperidol displayed a biphasic effect on I(Na) in guinea pig cardiac myocytes. High concentrations of haloperidol inhibited I(Na), 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 micromol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.