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


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


RESULTS
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.


CONCLUSIONS
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.
Cheng
Lu-Feng
LF
Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830054, China.
Yan
Dong
D
Turdi
Subat
S
Kerram
Parhat
P
D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism*
D018492:Dopamine Antagonists; D015222:Sodium Channels; D006220:Haloperidol