The antipsychotic and antiemetic drug prochlorperazine delays the ventricular repolarization of the in situ canine heart

J Pharmacol Sci. 2005 Jan;97(1):101-6. doi: 10.1254/jphs.fpj04038x. Epub 2005 Jan 15.

Abstract

Electropharmacological effect of the antipsychotic and antiemetic drug prochlorperazine was assessed using the halothane-anesthetized in vivo canine model (n = 5). Up to 10 times higher than the clinically relevant doses of prochlorperazine (< or = 3 mg/kg, i.v.) did not induce cardiohemodynamic collapse in the model. Meanwhile, clinically relevant to supratherapeutic doses (0.3 - 3 mg/kg, i.v.) prolonged the ventricular repolarization period in a dose-related and reverse-use dependent manner that could become proarrhythmic substrates. Thus, caution has to be paid on the use of prochlorperazine particularly for patients with risks of the elevated plasma drug concentration, compromised cardiac repolarization, and/or frequent ventricular premature beats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Antiemetics / adverse effects
  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Bundle of His / drug effects
  • Bundle of His / physiology
  • Cardiac Output / drug effects
  • Cardiac Output / physiology
  • Cardiac Pacing, Artificial / methods
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Electrocardiography / methods
  • Female
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Heart Ventricles / drug effects*
  • Infusions, Intravenous
  • Male
  • Prochlorperazine / adverse effects
  • Prochlorperazine / pharmacology*
  • Prochlorperazine / therapeutic use
  • Refractory Period, Electrophysiological / drug effects
  • Refractory Period, Electrophysiological / physiology
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Ventricular Function*
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology
  • Ventricular Pressure / drug effects
  • Ventricular Pressure / physiology

Substances

  • Antiemetics
  • Antipsychotic Agents
  • Prochlorperazine