title: Metabolism of levomepromazine in man.
abstract: The phenothiazine drug, levomepromazine (LM), is used in the treatment of psychiatric disorders and as an analgesic. A single 50 or 100 mg dose of LM was given to healthy male volunteers, and urine samples were collected for 24 h. The urine was treated with beta-glucuronidase, purified by solid-phase extraction, and analyzed on a GC-MS system for identification of LM metabolites. Mass spectra suggesting 14 different LM metabolites were obtained from the samples. Our of these, 13 spectra could be ascribed to specific metabolites, 5 of which have not previously been identified. All these 5 metabolites were hydroxylated at the phenothiazine nucleus. Although the applied method did not determine the positions of hydroxyl groups on phenothiazine nuclei. 3 of the 5 metabolites were identified as O-desmethyl 3-hydroxy LM, O-desmethyl 7-hydroxy LM, and N,O-didesmethyl 7-hydroxy LM, based on their chromatographic properties. In addition two metabolites, one being hydroxylated on the phenothiazine nucleus, and one being O-demethylated and hydroxylated on the nucleus, were found. It is suggested that these were 8-hydroxy LM and O-desmethyl 8-hydroxy LM. The concentrations of 3-hydroxy LM (free+conjugated) appeared to be much higher than the concentrations of any other metabolite in the samples.
authors.affiliation: Department of Pharmacology, University of Tromsø, Norway.
authors.forename: P A
authors.initials: PA
authors.lastname: Hals
authors.forename: S G
authors.initials: SG
authors.lastname: Dahl
mesh_terms: D014150:Antipsychotic Agents / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008728:Methotrimeprazine / Q000652:urine*
chemical_list: D014150:Antipsychotic Agents; D008728:Methotrimeprazine