Identification of metabolic pathways involved in the biotransformation of tolperisone by human microsomal enzymes.

The in vitro metabolism of tolperisone, 1-(4-methyl-phenyl)-2-methyl-3-(1-piperidino)-1-propanone-hydrochloride, a centrally acting muscle relaxant, was examined in human liver microsomes (HLM) and recombinant enzymes. Liquid chromatography-mass spectrometry measurements revealed methyl-hydroxylation (metabolite at m/z 261; M1) as the main metabolic route in HLM, however, metabolites of two mass units greater than the parent compound and the hydroxy-metabolite were also detected (m/z 247 and m/z 263, respectively). The latter was identified as carbonyl-reduced M1, the former was assumed to be the carbonyl-reduced parent compound.

Inhibition of effects of endogenously synthesized histamine disturbs in vitro human dendritic cell differentiation.

Histamine, a principal mediator in various physiological and pathological cell functions is synthesized from L-histidine exclusively by histidine decarboxylase, an enzyme, which is expressed in many tissues of mammalian organism. Histamine plays a role in various cellular functions, including cell differentiation. The aim of this study was to determine the presence and to characterize the role of the endogenously produced histamine during in vitro dendritic cell (DC) differentiation induced by interleukin-4 (IL-4) and granulocyte-monocyte colony stimulating factor (GM-CSF).

Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat.

RGH-1756, 1-(2-methoxy-phenyl)-4-(4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4-(14)C)-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with (14)C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed.

Effect of allylestrenol exposure during pregnancy on the activity of microsomal enzyme system (PSMO) of rat in the F1 and F2 generations.

Treatment of pregnant rats with allyestrenol on the 15th and 19th days of pregnancy induced the activity of enzyme system of adult offspring in females while it did not influence it in males. The steroid anticoncipient treatment of adults decreased the activity of some enzymes of the PSMO. The adulthood anticoncipient steroid treatment of rats which encountered allylestrenol in their fetal age compared to the only anticoncipient steroid treated group produces an increased activity of the majority of the tested parameters both in females and males.

Administration of benzpyrene and allylestrenol in fetal or neonatal periods of life: does it make difference in the microsomal activity?

Administration of allylestrenol or benzpyrene in fetal and neonatal periods of life make the rats susceptible to phenobarbiturate induction. Changes to controls could be observed in three of the enzyme activities tested (p-nitrophenol-hydroxylase, cytochrome P450 and aniline-hydroxylase), with a dominance of the p-nitrophenol-hydroxylase among them. There seemed to be no difference in the action of allylestrenol and benzpyrene, although treatment protocol in the neonatal period proved to be more effective.