Nuclear magnetic resonance analysis of methotrimeprazine (levomepromazine) hydroxylation in humans.

Two monohydroxylated metabolites of methotrimeprazine (levomepromazine), which previously have been identified in plasma and urine from psychiatric patients, were synthesized by nonenzymatic, FeCl2-catalyzed oxidation, isolated, and purified by preparative reversed-phase HPLC. Mass spectrometric analysis gave identical spectra for the two compounds, but did not reveal the positions of the OH groups. However, 1H NMR spectroscopy at 200 MHz demonstrated that one of the compounds, which had the shortest GC retention time on an OV-17 column, was hydroxylated in the 3-position on the phenothiazine nucleus, and that the other derivative was hydroxylated in the 7-position. The metabolism of methotrimeprazine differs, therefore, from that of its congener chlorpromazine, which is hydroxylated mainly in the 7-position in humans.

[1]  D. Cowan,et al.  Phenolic metabolites of thioridazine in man. , 1985, Xenobiotica; the fate of foreign compounds in biological systems.

[2]  S. Dahl,et al.  Gas chromatographic mass spectrometric identification of O-demethylated and mono-hydroxylated metabolites of levomepromazine in blood from psychiatric patients by selected ion recording with high resolution. , 1982, Biomedical mass spectrometry.

[3]  S. Dahl.  Active Metabolites of Neuroleptic Drugs: Possible Contribution to Therapeutic and Toxic Effects , 1982, Therapeutic drug monitoring.

[4]  S. Dahl,et al.  Identification of O-demethylated and ring-hydroxylated metabolites of methotrimeprazine (levomepromazine) in man. , 1982, Drug metabolism and disposition: the biological fate of chemicals.

[5]  S. Snyder,et al.  3H-Haloperidol binding to dopamine receptors in rat corpus striatum: influence of chlorpromazine metabolites and derivatives. , 1978, European journal of pharmacology.

[6]  S. Paul,et al.  Effect of metabolites of chlorpromazine on plasma prolactin levels in male rats. , 1977, European journal of pharmacology.

[7]  S. Dahl,et al.  Identification of nonpolar methotrimeprazine metabolites in plasma and urine by GLC-mass spectrometry. , 1977, Journal of pharmaceutical sciences.

[8]  S. Curry,et al.  Methods for study of fluphenazine kinetics in man , 1976, The Journal of pharmacy and pharmacology.

[9]  T. Sourkes,et al.  Effect of various chlorpromazine metabolites on amphetamine-induced stereotyped behaviour in the rat. , 1972, European journal of pharmacology.

[10]  S. R. Harris,et al.  Appearance of monohydroxylated chlorpromazine metabolites in the central nervous system. , 1971, Life sciences. Pt. 1: Physiology and pharmacology.

[11]  W. W. Westerfeld,et al.  The metabolism of chlorpromazine by liver microsomal enzyme systems. , 1967, The Journal of pharmacology and experimental therapeutics.

[12]  A. A. Manian,et al.  A comparative pharmacological study of a series of monohydroxylated and methoxylated chlorpromazine derivatives. , 1965, Life sciences.

[13]  H. Goldenberg,et al.  Side-chain degradation and ring hydroxylation of pehnothiazine tranquilizers. , 1965, The Journal of pharmacology and experimental therapeutics.

[14]  L. Lasagna,et al.  Methotrimeprazine: a new phenothiazine derivative with analgesic properties. , 1961, JAMA.

[15]  J. Huot,et al.  Levomepromazine (nozinan)-a new neuroleptic agent for treatment of senile patients. , 1959, Canadian Medical Association journal.

[16]  B. Brodie,et al.  Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation. , 1954, The Journal of biological chemistry.