Does chlorpromazine produce cardiac arrhythmia via the central nervous system?
The influence of the central nervous system in the production of phenothiazine-induced arrhythmia and death was examined in this study. In a series of cats, spinal cords were transected at the atlanto-occipital junction prior to the 1 mg/kg/min, i.v. infusion of chlorpromazine or thioridazine. No protection against drug-induced arrhythmia or death was afforded by this procedure. In other cats, 6OH-dopamine was administered prior to intravenous injection of atropine and infusion of chlorpromazine, 1 mg/kg/min. In these in situ denervated heart preparations, there was no protection against chlorpromazine-induced arrhythmia or death. In alpha-chloralose anesthetized cats, 0.5 mg chlorpromazine administered intracerebroventricularly did not induce arrhythmia or death, although blood pressure decreased initially. Thus, chlorpromazine or thioridazine do not appear to produce arrhythmia or death via a central locus and may instead be acting directly on myocardial conduction to produce arrhythmia and death.
Lipka
L J
LJ
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia.
Lathers
C M
CM
Roberts
J
J
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000503:physiopathology*; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects*; D003655:Decerebrate State; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D016627:Oxidopamine; D013563:Sympathectomy, Chemical; D013881:Thioridazine / Q000008:administration & dosage / Q000494:pharmacology
D006892:Hydroxydopamines; D016627:Oxidopamine; D013881:Thioridazine; D002746:Chlorpromazine