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p-Fluorophenylglycine in the urine of baboons treated with HPTP, the tetrahydropyridine analog of haloperidol.

Abstract：

:We report the presence of p-fluorophenylglycine (p-FPG) in the urine of six baboons treated with HPTP, the tetrahydropyridine dehydration product of haloperidol (HP). Oxidative N-dealkylation, the major metabolic pathway of HP, gives rise to 3-(4-fluorobenzoyl)propionic acid (p-FBPA). Subsequent beta-oxidation of p-FBPA produces p-fluorophenylacetic acid (p-FPA). The presence of p-FPA argues for the formation also of p-fluorophenylglyoxylic acid (p-FPGA) derived from beta-oxidation of p-FBPA. Plasma aminotransferases should convert p-FPGA to p-FPG. The presence of p-FPG in these animals suggest the presence of phenylglycine aminotransferases in the baboon and possibly also in other primates, including the human. Reports by other authors found that treatment with alpha-phenylglycine (alpha-PG), an "unnatural" amino acid, leads to striatal dopamine (DA) depletion in rabbits--an effect explained on the basis of alpha-PG competing with DA for the neuronal vesicular storage sites. We performed in vitro DA release assays in mouse striatal synaptosomal preparations but found that neither alpha-PG nor p-FPG released any DA. It therefore remains unclear whether p-FPG may be a contributing factor to neurologic side-effects such as tardive dyskinesia (TD) found in patients after long-term HP treatment.

journal_name

Life Sci

journal_title

Life sciences

authors

Mienie LJ,Bergh JJ,Bloomquist JR,Castagnoli N Jr,Steyn SJ,Van der Schyf CJ

doi

10.1016/s0024-3205(99)00274-x

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

535-42

issue

5

eissn

0024-3205

issn

1879-0631

pii

S002432059900274X

journal_volume

65

pub_type

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