In today's modern society, it seems to be more and more challenging to cope with life stresses. The effect of psychological stress on emotional and physical health can be devastating, and increased stress is associated with increased rates of heart attack, hypertension, obesity, addiction, anxiety and depression. This review focuses on the possibility of an influence of psychological stress on the metabolism of selected antidepressants (TCAs, SSRIs, SNRIs, SARIs, NDRIs a MMAs) and anxiolytics (benzodiazepines and azapirone), as patients treated with antidepressants and/or anxiolytics can still suffer from psychological stress. Emphasis is placed on the drug metabolism mediated by the enzymes of Phase I, typically cytochromes P450 (CYPs), which are the major enzymes involved in drug metabolism, as the majority of psychoactive substances are metabolized by numerous CYPs (such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2A6, CYP2D6, CYP3A4). As the data on the effect of stress on human enzymes are extremely rare, modulation of the efficacy and even regulation of the biotransformation pathways of drugs by psychological stress can be expected to play a significant role, as there is increasing evidence that stress can alter drug metabolism, hence there is a risk of less effective drug metabolism and increased side effects.

• Klíčová slova
• antidepressants, anxiolytics, cytochrome P450, drug metabolism, psychological stress,
• MeSH
• antidepresiva metabolismus   MeSH
• anxiolytika * metabolismus   MeSH
• biotransformace MeSH
• jaterní mikrozomy metabolismus   MeSH
• lidé MeSH
• psychický stres MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH
• anxiolytika * MeSH
• systém (enzymů) cytochromů P-450 MeSH

BACKGROUND: Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In the case of depression and schizophrenia, effective drug therapy is available but 30-50% of patients do not respond sufficiently to the initial treatment regimen. Apart from the development of new molecules, it is desirable to optimize treatment outcomes with agents that are currently available. Therapeutic drug monitoring (TDM) is a suitable and widely accepted approach for improving the efficacy and safety of these drugs. METHODS: A review of the relevant literature published between 2006 and January 2015. RESULTS AND CONCLUSIONS: This review describes major advances and drawbacks in the field of chromatography coupled with single or tandem mass spectrometry (LC-MS, LC-MS/MS and GC/MS) of selected antidepressants (agomelatine, vilazodone) and antipsychotics (iloperidone, asenapine, amisulpride, aripiprazole, melperone, zotepine, ziprasidone). The high specificity in combination with high sensitivity makes these techniques an attractive complementary method to traditional procedures used in routine practice for TDM.

• Klíčová slova
• antidepressant, antipsychotic, chromatography, drug, mass spectrometry, matrix effect, sample preparation,
• MeSH
• antidepresiva metabolismus   farmakokinetika   terapeutické užití   MeSH
• antipsychotika metabolismus   farmakokinetika   terapeutické užití   MeSH
• chemické techniky analytické metody   MeSH
• chromatografie metody   MeSH
• duševní poruchy farmakoterapie   MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• stabilita léku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH
• antipsychotika MeSH

Tissue-specific bioconcentration of selected antidepressants was studied in rainbow trout (Oncorhynchus mykiss) exposed to undiluted effluent from a Swedish municipal sewage treatment plant for 13 days. Citalopram, sertraline and venlafaxine were found in the brains and livers of most fish, but not in blood plasma or muscle. Venlafaxine was the only drug found in plasma (3/20 fish). Fluoxetine was not detected in any fish tissue, in accordance with a low concentration in the effluent and a comparably high limit of quantification in tissues. Concentrations of citalopram, sertraline and venlafaxine in fish brain were up to 1/12, 1/8 and 1/26, respectively, of the lowest concentrations found in the brains of mammals treated with therapeutic doses. Thus, given co-exposure to several antidepressants and an assumed similar potency in fish, the margin of safety for target-related effects in fish residing in effluent-dominated streams is relatively low. Furthermore, the non-detectable levels of these drugs in blood plasma suggest that analyses of concentrations in target tissues (brain) would be more informative in field studies and other studies with environmentally realistic exposure concentrations.

• Klíčová slova
• Brain, Caged fish, Liver, Rainbow trout, Selective serotonin reuptake inhibitors, Venlafaxine,
• MeSH
• antidepresiva metabolismus   MeSH
• chemické látky znečišťující vodu metabolismus   MeSH
• monitorování životního prostředí MeSH
• odpad tekutý - odstraňování metody   MeSH
• odpadní vody chemie   MeSH
• Oncorhynchus mykiss metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• chemické látky znečišťující vodu MeSH
• odpadní vody MeSH

The rapid and simple ultra performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination parent drugs: sertraline, fluoxetine, citalopram, paroxetine, venlafaxine, clozapine, olanzapine, quetiapine, risperidone, and their active and nonactive metabolites N-desmethylsertraline, norfluoxetine, desmethylcitalopram, didemethylcitalopram, N-desmethylvenlafaxine, O-desmethylvenlafaxine, N-desmethylclozapine, N-desmethylolanzapine, 2-hydroxyolanzapine and 9-hydroxyrisperidone in human serum. Precipitation of serum proteins was performed with a precipitation reagent consisting of 0.05% solution of ZnSO(4)·7H(2)O in acetonitrile/methanol (40:60, v/v). Alprenolol was used as an internal standard. Chromatographic separation was carried out on a BEH C18 column using gradient elution mobile phase A (2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v) and B (2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Electrospray in positive mode was used for ionization. Detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring. Analysis time was 5 min. Drugs were separated into three groups with low, medium and high levels. Correlation coefficients of calibration curves were in the range 0.995-1.000. Coefficients of variation were 4.2-9.5% for intra-assay and 3.0-11.9% for inter-assay. Recoveries were 87.1-110% for intra-assay and 88.1-108.2% for inter-assay. The method was fully validated and can be successfully applied for routine analyses.

• MeSH
• antidepresiva krev   metabolismus   MeSH
• antipsychotika krev   metabolismus   MeSH
• dospělí MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• antipsychotika MeSH

OBJECTIVES: Neurochemical studies on the etiopathogenesis of depression are also focusing on the transduction system beyond receptors. Trimeric G-proteins play a crucial role in the transmembrane signalling, signal amplification and intracellular processing. Abnormalities of G-protein levels are observed in subjects with depression, G-protein modulation is considered to play a role in the antidepressant mode of action. METHODS: We studied acute or chronic administration of antidepressants from different pharmacological groups. We used immunochemical estimation (ELISA) of the main types of G-protein alpha subunits from isolated membranes of C6 glioma cells and rat brain tissue. RESULTS: Significant elevation of G alpha q/11 subunits after chronic administration of sertraline and significant reduction of G alpha s subunit levels following both acute and chronic administrations of sertraline were found. In contrast, no significant effects on G alpha subunit levels following acute desipramine and moclobemide administration were observed in vitro. Chronic moclobemide effect in vivo is causing significant elevation of Galpha s and Galpha i1,2 subunit levels. CONCLUSIONS: Results show involvement of antidepressant drugs in the C6 glioma signal transduction cascades modulation in dependence on the antidepressant class. Significant influence in the cAMP system modulation is observed after administration both SSRI and MAOA inhibitors. Astrocytoma cells - C6 glioma cells also can offer a model system of the glia where modulation of cell signalization cascades can influence cell functioning and production of neurotrophic factor molecules relevant to the antidepressant treatment and depression etiopathogenesis.

• MeSH
• antidepresiva metabolismus   MeSH
• krysa rodu Rattus MeSH
• nádorové buněčné linie MeSH
• potkani Wistar MeSH
• proteiny vázající GTP - alfa-podjednotky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• proteiny vázající GTP - alfa-podjednotky MeSH

The connection between changes in lipid pattern in brain plasma membranes and long-term administration of therapeutically effective doses of antidepressants has not been sufficiently demonstrated so far. Therefore, we analyzed effect of antidepressants that differ in pharmacological selectivity on membrane lipid composition in the rat brain tissue. Laboratory rats were given desipramine, maprotiline, citalopram, moclobemide or lithium for a 4-week period. We observed a significant decrease in phosphatidylethanolamine representation after administration of maprotiline, citalopram and moclobemide when compared with controls. Membrane cholesterol content was decreased after desipramine administration and increased after citalopram or lithium treatment. Electroneutral phospholipids were decreased after the administration of all tested antidepressants except for desipramine. Decrease in phosphatidylserine was found following long-term administration of maprotiline or desipramine; relative representation of phosphatidylinositol was reduced after lithium treatment. Statistically significant negative correlation between cholesterol and electroneutral phospholipids was discovered. Membrane microviscosity evaluated by fluorescence anisotropy of membrane probes was only slightly decreased after desipramine and increased after citalopram administration. Hypothesis was supported that changes in brain neurotransmission produced by antidepressants could be, at least partially, associated with adaptive changes in membrane cholesterol and phospholipids.

• MeSH
• antidepresiva metabolismus   MeSH
• časové faktory MeSH
• fosfolipidy metabolismus   MeSH
• fyziologická adaptace účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• membránové lipidy metabolismus   MeSH
• mozek účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• fosfolipidy MeSH
• membránové lipidy MeSH

Metabolites of drug VUFB 15468 present in the urine of rats, mice and dogs and in rat faeces after peroral administration were determined qualitatively. The relative representation of the individual metabolites in the urine of rats and mice was determined radiometrically after p. o. administration of [3H]VUFB 15468. For qualitative demonstration the metabolites were extracted; they were detected, partially identified and purified by thin-layer chromatography and then analyzed by mass spectrometry and IR-spectrometry. Structures of 11 metabolites were completely or partially determined in rat urine. Five of them were also found in rat faeces, one in murine urine and five in canine urine. In all animal species also unchanged VUFB 15468 was found. For quantification of the individual metabolites and VUFB 15468, TLC-radiometry and liquid scintillation spectrometry were used in rats and mice. Of the relative representation of metabolites, about one third is unchanged VUFB 15468, the rest are metabolites. In mice, the proportion of unchanged VUFB 15468 is much higher, about two thirds.

• MeSH
• antidepresiva metabolismus   MeSH
• benzylaminy metabolismus   MeSH
• biotransformace MeSH
• inbrední kmeny myší MeSH
• inbrední kmeny potkanů MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• benzylaminy MeSH
• VUBF 15468 MeSH Prohlížeč

• MeSH
• antidepresiva metabolismus   MeSH
• imipramin metabolismus   MeSH
• lidé MeSH
• sodík farmakologie   MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• imipramin MeSH
• sodík MeSH

• MeSH
• antagonisté serotoninu MeSH
• antidepresiva metabolismus   terapeutické užití   MeSH
• bipolární porucha farmakoterapie   MeSH
• chemické jevy MeSH
• chemie MeSH
• chování zvířat účinky léků   MeSH
• deprese farmakoterapie   MeSH
• inhibitory MAO terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• noradrenalin antagonisté a inhibitory   MeSH
• systém hypofýza - nadledviny účinky léků   MeSH
• trankvilizéry terapeutické užití   MeSH
• vodní a elektrolytová rovnováha MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antagonisté serotoninu MeSH
• antidepresiva MeSH
• inhibitory MAO MeSH
• noradrenalin MeSH
• trankvilizéry MeSH