Zotepin je derivátem dibenzothiepinové skupiny antipsychotik, který náleží mezi multireceptorové antagonisty (MARTA). Silněji blokuje serotoninové než dopaminové receptory, jejichž obsazenost nepřevyšuje 80 % a je málo limbicky selektivní. Na rozdíl od jiných antipsychotik blokuje reuptake noradrenalinu a působí jen slabě kataleptogenně. V klinických studiích byl zotepin stejně účinný jako klasická antipsychotika v ovlivnění pozitivních schizofrenních příznaků a účinnější v redukci negativní symptomatiky a anxiety/deprese. V menší studii byl stejně úspěšný jako clozapin, včetně ovlivnění kognitivní dysfunkce. Dlouhodobé podávání potvrdilo vyšší profylaktickou účinnost vůči placebu. Zotepin byl zatížen významně nižším výskytem extrapyramidových reakcí oproti haloperidolu, ale iniciálně vyvolával sedaci, hypotenzi, hyperprolaktinemii, případně působil prokonvulzivně a prodlužoval QT interval. K definitivnímu určení klinického postavení zotepinu jsou nutné srovnávací studie s jinými antipsychotiky 2. generace.

Zotepine is a derivative of the dibenzothiepine group of antipsychotics ranking among the multireceptor antagonists (MARTA). It blocks rather serotonin than dopamine receptors, whose occupation rate does not exceed 80%. Its limbic selectivity is low. In contrast to other antipsychotics, zotepine inhibits the noradrenaline reuptake and has only weak cataleptogenic effect. In clinical trials, zotepine suppressed positive schizophrenic symptoms as effectively as classic antipsychotics, and was even more effective in reducing the negative syptoms and anxiety/depression. A small trial showed it as effective as clozapine in managing cognitive dysfunction. Long-term administration confirmed the higher prophylactic effects of zotepine compared with placebo. Zotepine showed a significantly lower incidence of extrapyramidal side effects as compared to haloperidol, but provoked initial sedation, hypotension, hyperprolactinemia, and had proconvulsive effects; it also led to the QT period prolongation. The conclusion about the clinical status of zotepine will require clinical comparisons with other antipsychotics of the 2nd generation.

• Klíčová slova
• ZOLEPTIL (AVALANCHE),
• MeSH
• antipsychotika farmakologie   chemie   škodlivé účinky   MeSH
• dibenzothiepiny terapeutické užití   MeSH
• hodnocení léčiv MeSH
• lidé MeSH
• placebo MeSH
• receptory dopaminové MeSH
• receptory serotoninové MeSH
• schizofrenie farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

• MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• antipsychotika farmakologie   MeSH
• benzodiazepiny farmakologie   MeSH
• dibenzothiepiny farmakologie   MeSH
• dizocilpinmaleát antagonisté a inhibitory   farmakologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• klozapin farmakologie   MeSH
• krysa rodu rattus MeSH
• risperidon farmakologie   MeSH
• úleková reakce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• antipsychotika terapeutické užití   MeSH
• dospělí MeSH
• lidé MeSH
• psychotické poruchy farmakoterapie   MeSH
• risperidon terapeutické užití   MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

V práci sa prezentuje širokospektrálny terapeutický účinok zotepinu. Autor dokumentuje túto skutočnosť na súbore 228 pacientov, rozdelených do 16 podsúborov podľa vedúcej psychiatrickej diagnózy, pre ktorú boli v terapii. Najpoèetnejšia je skupina 43 pacientov liečených pre paranoidnú schizofréniu, u ktorých bola použitá najèastejšie monoterapia zotepinom (u 17 pacientov), u 13 pacientov bol zotepin kombinovaný s iným neuroleptikom per os a u 13 pacientov s depotným neuroleptikom. U pacientov so schizofréniou sme zistili v 48,8 % prípadoch prevažujúci terapeutický efekt na pozitívnu symptomatológiu, u 51,2 % prípadov na negatívnu symptomatológiu. Spomedzi nežiadúcich úèinkov sme pozorovali ako najèastejšiu únavnosť a inhibíciu – u 8,8 % pacientov, extrapyramídové prejavy malo 5,7 % pacientov. Konštatujeme, že zotepin je preparát so širokým spektrom terapeutického využitia. Jeho výhodou je aj rýchly nástup účinku, nízky výskyt nežiadúcich úèinkov a možnosť bezpečnej kombinácie s inými psychofarmakami.

In this study we present a group to 228 patients, divided into 16 subgroups based on psychiatric diagnosis. The most numerous group is 43 patients, treated for paranoid schizophrenia, when monotherapy with zotepin was used the most frequently (in 17 patients), in 13 patients was zotepin combined with other neuroleptic drugs per os, in 13 patients it was combined with depot neuroleptic drugs. In patients with schizophrenia, we found a predominant therapeutic effect zotepin on positive sympto- matology in 48.8 % of cases and on negative symptomatology in 51.2 % of cases. As to the adverse effects, weariness and inhibition were observed the most frequently – in 8.8 % of patients, 5.7 % of patients had extrapyramidal symptoms. We note that zotepin is a drug with a broad range of therapeutic applicability. Its advantage is the rapid onset of action, low incidence of adverse effects and safe option in combination with other drugs.

• Klíčová slova
• zotepin, terapeutický účinok,
• Publikační typ
• abstrakty MeSH

• Klíčová slova
• QUETIAPINE, ZIPRASIDON, ZOTEPINE,
• MeSH
• amisulprid MeSH
• antipsychotika aplikace a dávkování   farmakologie   chemie   MeSH
• hodnocení léčiv MeSH
• registrace MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: The main objective was to evaluate the effect of five second-generation antipsychotics (amisulpride, quetiapine, olanzapine, risperidone, and zotepine) on prolactinaemia during 6 week therapy in 433 female in-patients with mainly schizophrenic disorders. Secondary objectives included identification of dynamics of change in serum prolactin levels and correlations of changes of prolactinaemia with some demographic and clinical parameters. METHODS: The trial was a prospective, open-label, single-center one with a flexible dosing of SGAs. The therapeutic effect of SGAs was assessed by a change of scores of CGI-S and CGI-I scales from a baseline to the endpoint. Blood samples were taken in the morning under fasting condition. RESULTS: Amisulpride and risperidone increased prolactinaemia significantly in 100% of patients, as early as after week 1 of the therapy. Quetiapine and zotepine relatively reduced prolactinaemia significantly, as early as from week 1 of the quetiapine treatment. Olanzapine led to a transient mild prolactin elevation. The much lower prevalence of hyperprolactinaemia over 2 000 mIU/l differentiates olanzapine from amisulpride and risperidone. Prolactin elevation did not correlate with age, menopausal condition, therapeutic efficacy, antipsychotic daily dose, serum levels of lipids and glucose. There was significant correlation with first vs. subsequent psychotic episodes, weight, EPS and serum levels of thyroid hormones. CONCLUSION: Amisulpride and risperidone had marked and early prolactin elevating effects, requiring, therefore, more frequent monitoring of prolactinaemia and associated undesirable effects and risks than olanzapine, quetiapine and zotepine.

• MeSH
• antipsychotika škodlivé účinky   terapeutické užití   MeSH
• benzodiazepiny MeSH
• dospělí MeSH
• financování organizované MeSH
• hyperprolaktinemie chemicky indukované   krev   MeSH
• klinické zkoušky jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• neparametrická statistika MeSH
• prolaktin krev   MeSH
• prospektivní studie MeSH
• risperidon škodlivé účinky   terapeutické užití   MeSH
• schizofrenie farmakoterapie   komplikace   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sulpirid analogy a deriváty   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

Assessment of drug-induced mitochondrial dysfunctions is important in drug development as well as in the understanding of molecular mechanism of therapeutic or adverse effects of drugs. The aim of this study was to investigate the effects of three typical antipsychotics (APs) and seven atypical APs on mitochondrial bioenergetics. The effects of selected APs on citrate synthase, electron transport chain complexes (ETC), and mitochondrial complex I- or complex II-linked respiratory rate were measured using mitochondria isolated from pig brain. Complex I activity was decreased by chlorpromazine, haloperidol, zotepine, aripiprazole, quetiapine, risperidone, and clozapine. Complex II + III was significantly inhibited by zotepine, aripiprazole, quetiapine, and risperidone. Complex IV was inhibited by zotepine, chlorpromazine, and levomepromazine. Mitochondrial respiratory rate was significantly inhibited by all tested APs, except for olanzapine. Typical APs did not exhibit greater efficacy in altering mitochondrial function compared to atypical APs except for complex I inhibition by chlorpromazine and haloperidol. A comparison of the effects of APs on individual respiratory complexes and on the overall mitochondrial respiration has shown that mitochondrial functions may not fully reflect the disruption of complexes of ETC, which indicates AP-induced modulation of other mitochondrial proteins. Due to the complicated processes associated with mitochondrial activity, it is necessary to measure not only the effect of the drug on individual mitochondrial enzymes but also the respiration rate of the mitochondria or a similar complex process. The experimental approach used in the study can be applied to mitochondrial toxicity testing of newly developed drugs.

• MeSH
• antipsychotika toxicita   MeSH
• energetický metabolismus účinky léků   MeSH
• mitochondrie účinky léků   patologie   MeSH
• mozek účinky léků   metabolismus   MeSH
• prasata MeSH
• respirační komplex I účinky léků   metabolismus   MeSH
• respirační komplex II účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• Klíčová slova
• psychiatři - konference(Kyoto,1990) - sborníky prací, neuroleptika - užití terapeutické - schizofrenie - sborníky prací,

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• farmacie a farmakologie
• psychiatrie
• neurologie

A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.

• MeSH
• chromatografie kapalinová metody   MeSH
• lidé MeSH
• limita detekce MeSH
• lineární modely MeSH
• monitorování léčiv metody   MeSH
• psychotropní léky krev   farmakokinetika   moč   MeSH
• reprodukovatelnost výsledků MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The goal of this review is to summarize the results of head to head efficacy studies that compare second generation antipsychotics in the treatment of schizophrenia and related disorders. METHODS: A literature search through the Medline database and Google was conducted. Articles published up to September 2005 were included. Abstracts from conference papers and posters were not included. RESULTS: Randomized controlled trial data on possible differences in efficacy among atypical antipsychotics are limited. Moreover, the comparison is difficult, as studies differ in outcome measures. The results indicate that first-line second-generation antipsychotics (amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone and zotepine) show comparable efficacy. CONCLUSION: Possible new studies should focus on long-term effects, including cost-effectiveness, quality of life, social functioning and service utilization.

• MeSH
• antipsychotika škodlivé účinky   terapeutické užití   MeSH
• financování organizované MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• psychiatrické posuzovací škály MeSH
• randomizované kontrolované studie jako téma MeSH
• schizofrenie diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH