ECG‐Changes Induced by Phenothiazine Drugs in the Anaesthetized Rat

The ECG has been recorded in barbiturate anaesthetized rats during intravenous infusion of levomepromazine, chlorpromazine, prochlorperazine and perphenazine. All the drugs decreased impulse‐generation and propagation in the heart. The magnitude of the changes in heart rate, PQ‐ QRS‐ and QT‐time was dose dependent, and the relative order of potency of the drugs was as follows: 1. perphenazine and prochlorperazine, 2. chlorpromazine and 3. levomepromazine. Perphenazine, prochlorperazine, chlorpromazine and levomepromazine in 2.5 × 10‐5 M concentration increased the PQ‐time to about 130 %, 128 %, 122 % and 117 % respectively, of the PQ‐time before infusion. The magnitude of the changes in rate, QT‐ and QRS‐intervals was in the same range. At higher concentrations, all the drugs caused AV‐block of variable degree. Qualitatively these changes are similar to those induced by the drugs in the isolated perfused rat heart; quantitatively, however, these in vivo findings do not correspond to the in vitro findings recently described by the present author. Levomepromazine which in vitro was unique in changing the ECG‐pattern at much lower concentrations than the other phenothiazine derivatives, is less potent than perphenazine, prochlorpromazine and chlorpromazine in vivo. Possible explanations for this discrepancy are discussed.