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

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Abstract
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.