THE EFFECT OF CHLORPROMAZINE, METYRAPONE, IMIPRAMINE AND SKF 525‐A ON THE HEPATIC FIRST PASS ELIMINATION OF PROPRANOLOL IN THE PITHED RAT

1 The effect of chlorpromazine, metyrapone, imipramine and SKF 525‐A on the hepatic first pass elimination of propranolol has been studied in the pithed rat. 2 The effect of chlorpromazine, metyrapone, imipramine and SKF 525‐A on the inhibition caused by propranolol of an elicited electrically induced tachycardia has also been studied. 3 The hepatic first pass elimination of propranolol was reduced following pretreatment with chlorpromazine, imipramine and SKF 525‐A but was not affected by pretreatment with metyrapone. 4 Chlorpromazine, imipramine and SKF 525‐A all resulted in an increased propranolol blood concentration after hepatic portal vein administration which was associated with decreased formation of metabolites and an enhanced inhibition of an electrically induced tachycardia.