Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Incubation of phencyclidine (
PCP
) with rabbit liver microsomes and Na14CN resulted in the metabolically dependent formation of a 14C-labeled cyano adduct of the drug. After isolation by HPLC, this compound was identified as the alpha-aminonitrile [1-(1-phenylcyclohexyl)-2-cyanopiperidine] derivative of
PCP
by use of chemical-ionization and gas-chromatographic coupled electron-impact mass spectrometry. Synthetic alpha-aminonitrile exhibited identical chemical properties and comigrated in HPLC and
GLC
with the metabolism derived cyano adduct. Molecular identification of the adduct formed by cyanide trapping provided evidence for the formation of an iminium ion during
PCP
metabolism. Quantitative estimation by HPLC demonstrated that the alpha-aminonitrile accounted for over 50% of the
PCP
metabolized in 30 min by hepatic microsomes in vitro. Metabolism-dependent covalent binding of [3H]
PCP
to rabbit liver microsomal proteins was inhibited by cyanide ion in a concentration-dependent manner with an IC50 value of 57 microM. The concentrations of cyanide ion used in these experiments did not significantly inhibit the metabolism of
PCP
. These results support our suggestions that iminium ion formation may represent an important intermediary step in the metabolism of
PCP
and that such a reactive electrophilic species may be capable of covalent interactions with nucleophilic groupings on microsomal macromolecules.
...
PMID:Metabolism of phencyclidine. The role of iminium ion formation in covalent binding to rabbit microsomal protein. 613 Sep 25
A
GLC
assay for phencyclidine (
PCP
) is described, which also simultaneously measures three primary hydroxylated metabolites formed from incubating
PCP
in tissue homogenates. Using the FID detector, the limits of reliable detection of
PCP
and both monohydroxy metabolites, 4-phenyl-4-piperidino-cyclohexanol, 2, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine, 3, are 0.02 mumol per injection and 0.05 mumol for the dihydroxy metabolite, 4-(4'-hydroxypiperidino)-4-phenylcyclohexanol, 2A. Baseline separation of an compounds was achieved and coefficients of variation (between-run) was 3-6% for
PCP
, and both monohydroxy metabolites, and 12% for the dihydroxy metabolite. A GCMS assay is also reported herein for the analysis of
PCP
at low levels, and can detect 5 pmol per injection of
PCP
, with a linear standard curve from 50 to 2000 pmol.
...
PMID:A gas-liquid chromatography assay for phencyclidine and its metabolites. 720 59
