Distribution, excretion and metabolism of neuroleptics of the butyrophenone type: Part I. Excretion and metabolism of haloperidol and nine related butyrophenone-derivatives in the Wistar rat

doi:10.1016/0014-2999(67)90065-9

European Journal of Pharmacology

Volume 1, Issue 1, January 1967, Pages 47-57

https://doi.org/10.1016/0014-2999(67)90065-9 Get rights and content

Abstract

The excretion pattern over a 96 hour period and the metabolic pathway of specifically tritium-labelled haloperidol and 9 related neuroleptic butyrophenones has been investigated after subcutaneous administration of biologically active doses to male Wistar rats.

The excretion of radioactive material in urine and feces was maximal within 24 hours. Then the excretion decreased quickly and less than 1% was eliminated in both the urine and the feces after 72 hours. After 96 hours there was still radioactive material present in the body. This residual amount decreased in the order: seperidol > trifluperidol > haloperidol ⩾ bromoperidol > benperidol ⩾ morepone > haloanisone = floropipamide ⩾ droperidol.

Oxidative N-dealkylation is a major metabolic pathway giving rise to β-(p-fluorobenzoyl)-propionic acid, which is rapidly metabolised to p-fluorophenylacetic acid and its glycine conjugate p-fluorophenaceturic acid.

The metabolites were identified by the inverse isotope dilution method.

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Distribution, excretion and metabolism of neuroleptics of the butyrophenone type: Part I. Excretion and metabolism of haloperidol and nine related butyrophenone-derivatives in the Wistar rat

Abstract

Biochem. Pharmacol.

Intern. Rev. Neurobiol.

Influence de 15 neuroleptiques (butyrophénones et phénothiazines) sur les variations de la teneur du cerveau en noradrénaline et l'activité du rat dans le test d'autostimulation

Arch. Int. Pharmacodyn.

4-substituted piperidines. II. Reaction of 1-benzyl-4-cyano-4-t-aminopiperidines with organo metallic compounds

J. Med. Chem.

4-substituted piperidines. III. Reduction of 1-benzyl-4-cyano-4-t-aminopiperidines with lithiumaluminium hydride

J. Med. Chem.

Chemistry and pharmacology of CNS depressants related to 4-(4-hydroxy-4-phenylpiperidino) butyrophenone. Part I — Synthesis and screening data in mice

J. Med. Pharm. Chem.