Metabolomic studies represent a promising tool for early diagnosis of schizophrenia. The aim of this study was to find differences in the steroid spectrum in patients and controls, and to assess the diagnosis of schizophrenia by building a predictive model based on steroid data. Thirty-nine serum steroids (22 neuroactive steroids and their metabolites and 17 polar conjugates) representing steroid metabolome were measured by gas chromatography-mass spectrometry in 22 drug-naive (first episode) schizophrenia patients (13 men and 9 women) before and after six-month treatment with atypical antipsychotics. The results were compared to the data from healthy subjects (22 males, 25 females). In summary the following significant differences were found: (1) In both sexes higher levels of pregnenolone sulfate and sulfated 5α- as well as 5β-saturated metabolites of C21-steroids in progesterone metabolic pathway were found in patients, pointing to decreased activity of sulfatase. (2) In a few instances decreased levels of the respective 5α-metabolites of C21 steroids were found in patients. (3) As C19 steroids concern, in both sexes there were considerably lowered levels of 5β-reduced metabolites in patients. On the other hand, with only a few exceptions, the treatment did not significantly influence most steroid levels. Further, to assess the relationships between schizophrenia status and steroid levels and to build the predictive model of schizophrenia, multivariate regression with reduction of dimensionality (the method of orthogonal projections to latent structures, OPLS) was applied. Irrespective of the small number of patients, use of this model enabled us to state the diagnosis of schizophrenia with almost 100% sensitivity. Our findings suggest that the assessment of steroid levels may become a valid and accurate laboratory test in psychiatry. A limitation of our study is the absence of subjects with a diagnosis other than schizophrenia, so we cannot conclude whether the results are specific for schizophrenia. On the other hand, steroid metabolome model may be used as a diagnostic tool for further studies.
- MeSH
- amisulprid MeSH
- antipsychotika terapeutické užití MeSH
- benzodiazepiny terapeutické užití MeSH
- biologické modely MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolom * MeSH
- metabolomika metody MeSH
- mladý dospělý MeSH
- olanzapin MeSH
- schizofrenie diagnóza farmakoterapie metabolismus MeSH
- steroidy krev metabolismus MeSH
- studie případů a kontrol MeSH
- sulpirid analogy a deriváty terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amisulprid MeSH
- antipsychotika MeSH
- benzodiazepiny MeSH
- olanzapin MeSH
- steroidy MeSH
- sulpirid MeSH
Spatial navigation attracts the attention of neuroscientists as an animal analogue of human declarative memory. The Carousel maze is a dry-land navigational paradigm, which proved to be useful in studying neurobiological substrates of learning. The task involves avoidance of a stable sector on a rotating arena and is highly dependent upon the hippocampus. The present study aims at testing hypothesis that sulpiride (a centrally-active dopamine D2-like receptor antagonist) and propranolol (a beta-blocker) impair spatial learning in the Carousel maze after combined systemic administration. These doses were previously shown to be subthreshold in this task. Results showed that both substances affected behavior and significantly potentiated their negative effects on spatial learning. This suggests central interaction of both types of receptors in influencing acquisition of this dynamic-environment task.
- MeSH
- antagonisté dopaminu D2 * MeSH
- antagonisté dopaminu aplikace a dávkování MeSH
- beta blokátory aplikace a dávkování MeSH
- bludiště - učení účinky léků fyziologie MeSH
- krysa rodu Rattus MeSH
- potkani Long-Evans MeSH
- propranolol aplikace a dávkování MeSH
- prostorové chování účinky léků fyziologie MeSH
- psychomotorický výkon účinky léků fyziologie MeSH
- receptory dopaminu D2 fyziologie MeSH
- sulpirid aplikace a dávkování MeSH
- synergismus léků 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
- antagonisté dopaminu D2 * MeSH
- antagonisté dopaminu MeSH
- beta blokátory MeSH
- propranolol MeSH
- receptory dopaminu D2 MeSH
- sulpirid MeSH
New bioanalytical SPE-HPLC-PDA-FL method for the determination of the neuroleptic drug tiapride and its N-desethyl metabolite was developed, validated and applied to xenobiochemical and pharmacokinetic studies in humans and animals. The sample preparation process involved solid-phase extraction of diluted plasma spiked with sulpiride (an internal standard) using SPE cartridges DSC-PH Supelco, USA. Chromatographic separation of the extracts was performed on a Discovery HS F5 250 mm × 4 mm (Supelco) column containing pentafluorophenylpropylsilyl silica gel. Mobile phase (acetonitrile-0.01 M phosphate buffer pH=3, flow rate 1 ml min(-1)) in the gradient mode was employed in the HPLC analysis. Tandem UV photodiode-array→fluorescence detection was used for the determination of the analytes. Low concentrations of tiapride and N-desethyl tiapride were determined using a more selective fluorescence detector (λ(exc.)/λ(emiss.)=232 nm/334 nm), high concentrations (500-6000 pmol ml(-1)) using a UV PDA detector at 212 nm with a linear response. Each HPLC run lasted 15 min. Lower limits of quantification (LLOQ) for tiapride (N-desethyl tiapride) were found to be 8.24 pmol ml(-1) (10.11 pmol ml(-1)). The recoveries of tiapride ranged from 89.3 to 94.3%, 81.7 to 86.8% for internal standard sulpiride and 90.9 to 91.8% for N-desethyl tiapride.
- MeSH
- extrakce na pevné fázi MeSH
- fluorescenční spektrometrie metody MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- limita detekce MeSH
- lineární modely MeSH
- mladý dospělý MeSH
- reprodukovatelnost výsledků MeSH
- spektrofotometrie ultrafialová metody MeSH
- sulpirid krev MeSH
- tiapamil-hydrochlorid analogy a deriváty krev farmakokinetika MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- sulpirid MeSH
- tiapamil-hydrochlorid MeSH
OBJECTIVES: The aim of our study was to assess the time to 'first improvement' associated with specific atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders. METHODS: This study involved a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs and TAPs, for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 296 teenage patients (141 males, 155 females; mean age 16.0 ± 1.5 years). The time to first improvement could be estimated in 258 patients; of these, 195 patients (76%) had been treated with AAPs and 63 patients (24%) with TAPs. We found that most patients were taking risperidone (N = 96), followed by olanzapine (64 patients). Other patient numbers were as follows: ziprasidone (16 patients), quetiapine (12 patients), clozapine (7 patients), haloperidol (15 patients), perphenazine (28 patients), and sulpiride (20 patients). RESULTS: The mean time to first improvement was 6.9 (± 4.2) days in the AAP group and 5.8 (± 3.5) days in the TAP group; the difference was significant at the trend level (p=0.063). With respect to individual drugs, the mean time to first improvement was 7.1 (± 4.1) days for risperidone, 6.7 (± 4.2) days for olanzapine, 6.5 (± 5.2) days for ziprasidone, 6.1 (± 4.4) days for quetiapine, 7.4 (± 3.0) days for clozapine, 5.2 (± 2.4) days for haloperidol, 5.9 (± 3.8) days for perphenazine, and 6.0 (± 3.9) days for sulpiride. Differences among drugs were not significant (p=0.680). CONCLUSIONS: Analysis revealed a significant group level trend indicating that typical antipsychotic drugs have faster onsets of action than atypical antipsychotic drugs.
- MeSH
- antipsychotika terapeutické užití MeSH
- benzodiazepiny terapeutické užití MeSH
- časové faktory MeSH
- chorobopisy MeSH
- dibenzothiazepiny terapeutické užití MeSH
- haloperidol terapeutické užití MeSH
- klozapin terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- olanzapin MeSH
- perfenazin terapeutické užití MeSH
- piperaziny terapeutické užití MeSH
- psychotické poruchy farmakoterapie MeSH
- quetiapin fumarát MeSH
- risperidon terapeutické užití MeSH
- schizofrenie farmakoterapie MeSH
- sulpirid terapeutické užití MeSH
- thiazoly terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antipsychotika MeSH
- benzodiazepiny MeSH
- dibenzothiazepiny MeSH
- haloperidol MeSH
- klozapin MeSH
- olanzapin MeSH
- perfenazin MeSH
- piperaziny MeSH
- quetiapin fumarát MeSH
- risperidon MeSH
- sulpirid MeSH
- thiazoly MeSH
- ziprasidone MeSH Prohlížeč
AIM: The main objective was to identify the occurrence of adverse events associated with amisulpride when combined with antidepressants (ADs). METHODS: A non-interventional questionnaire-based study focussed on identification of occurrence and tolerance of combinations of amisulpride with ADs under common clinical practice conditions. RESULTS: Combinations of amisulpride with ADs were administered to 3178 patients suffering from depression. The average daily dose of amisulpride was 54.8 ± 17 mg (range 50-150 mg/day). The most frequently administered ADs were SSRIs. A total of 4463 adverse events were recorded in 1624 (51%) of all treated patients. The most frequent adverse event was weight gain, followed by headache, fatigue and sleepiness. Only 2% of all adverse events were evaluated as adverse events of medium or high intensity. Higher occurrences of some adverse events were noted for specific combinations. CONCLUSION: The advantages of AD combinations undoubtedly include administration of lower doses and a reduction of adverse events associated with higher doses of individual ADs. On the other hand, adverse events can also sum. Nevertheless it is generally agreed that, in some patients, a combination of ADs, with different mechanisms of action, can be considered safe and effective polypharmacy.
- MeSH
- amisulprid MeSH
- antidepresiva škodlivé účinky MeSH
- depresivní poruchy farmakoterapie MeSH
- dospělí MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- sulpirid škodlivé účinky analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amisulprid MeSH
- antidepresiva MeSH
- selektivní inhibitory zpětného vychytávání serotoninu MeSH
- sulpirid MeSH
The processing of spatial information is the focus of interest for many cognitive neuroscientists. Approximately 10 years ago, a novel behavioral paradigm called active allothetic place avoidance (AAPA) was designed allowing the simultaneous assessment of locomotor and spatial behavior. The present study describes the effect of the combined treatment of Long-Evans rats with alpha1-adrenergic and D2 antagonists prazosin (1mg/kg and 2 mg/kg) and sulpiride (10 mg/kg and 30 mg/kg) on locomotion and avoidance behavior in the AAPA task. Results show that co-application of both drugs leads to disturbances in locomotion and avoidance in rats at the doses, which caused no impairments when administered independently. This finding suggests that both types of receptors act synergistically to regulate locomotion and possibly spatial behavior.
- MeSH
- alfa blokátory aplikace a dávkování MeSH
- alfa-1-adrenergní receptory účinky léků metabolismus MeSH
- analýza rozptylu MeSH
- antagonisté dopaminu aplikace a dávkování MeSH
- asociační učení účinky léků fyziologie MeSH
- interakce mezi receptory a ligandy fyziologie MeSH
- krysa rodu Rattus MeSH
- pohybová aktivita účinky léků fyziologie MeSH
- potkani Long-Evans MeSH
- prazosin aplikace a dávkování MeSH
- prostorové chování účinky léků fyziologie MeSH
- receptory dopaminu D2 účinky léků metabolismus MeSH
- sulpirid aplikace a dávkování MeSH
- synergismus léků MeSH
- učení vyhýbat se účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- životní prostředí 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
- alfa blokátory MeSH
- alfa-1-adrenergní receptory MeSH
- antagonisté dopaminu MeSH
- prazosin MeSH
- receptory dopaminu D2 MeSH
- sulpirid 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
- amisulprid MeSH
- antipsychotika škodlivé účinky terapeutické užití MeSH
- benzodiazepiny škodlivé účinky terapeutické užití MeSH
- dibenzothiazepiny škodlivé účinky terapeutické užití MeSH
- dibenzothiepiny škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- hyperprolaktinemie krev chemicky indukované MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- neparametrická statistika MeSH
- olanzapin MeSH
- prolaktin krev MeSH
- prospektivní studie MeSH
- quetiapin fumarát MeSH
- risperidon škodlivé účinky terapeutické užití MeSH
- schizofrenie komplikace farmakoterapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sulpirid škodlivé účinky analogy a deriváty terapeutické užití 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
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- amisulprid MeSH
- antipsychotika MeSH
- benzodiazepiny MeSH
- dibenzothiazepiny MeSH
- dibenzothiepiny MeSH
- olanzapin MeSH
- prolaktin MeSH
- quetiapin fumarát MeSH
- risperidon MeSH
- sulpirid MeSH
- zotepine MeSH Prohlížeč
Dopamine-mediated neurotransmission is widely studied with respect to motivation, motor activity and cognitive processes. The aim of the present study was to evaluate the role of D2 receptors in the behavior of rats in the active allothetic place avoidance (AAPA) task. D2 receptor agonist quinpirole and antagonist sulpiride were administered intraperitoneally 20min prior to behavioral testing. Administration of quinpirole led to dose-dependent increase of locomotion; the spatial efficiency was spared across the dose range studied (0.05-1.0mg/kg). In contrast, sulpiride decreased locomotor activity at a dose not influencing spatial efficiency (60mg/kg); the highest dose of sulpiride (100mg/kg) caused a deficit in both locomotor and spatial behaviors. The results suggest a relatively lesser importance of D2 receptors for spatial efficiency in the AAPA task, with a predominant influence of D2 receptor ligands on motor activity.
- MeSH
- agonisté dopaminu farmakologie MeSH
- analýza rozptylu MeSH
- antagonisté dopaminu farmakologie MeSH
- chinpyrol farmakologie MeSH
- chování zvířat účinky léků MeSH
- krysa rodu Rattus MeSH
- lokomoce účinky léků MeSH
- potkani Long-Evans MeSH
- prostorové chování účinky léků MeSH
- receptory dopaminu D2 fyziologie MeSH
- sulpirid farmakologie MeSH
- učení vyhýbat se účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva 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
- agonisté dopaminu MeSH
- antagonisté dopaminu MeSH
- chinpyrol MeSH
- receptory dopaminu D2 MeSH
- sulpirid MeSH
OBJECTIVES: Amisulpride in antipsychotic doses can induce hyperprolactinemia. The aim of this study was to prove whether the same is true for low doses of amisulpride. METHODOLOGY: Plasma prolactin levels were measured in 5 males and 5 females with depressive symptoms who were treated with 50 mg of amisulpride per day as an augmentation to antidepressants (n=5), benzodiazepine anxiolytics (n=8) or in monotherapy (n=1). Six of these patients were assessed prior to onset of amisulpride treatment and after 10 days of amisulpride use. Four patients had been using amisulpride for more than a month. RESULTS: There was a significant increase of prolactin levels from mean 16+/-6 ng/ml to 113+/-65 ng/ml (median 14.5 ng/ml to median 92 ng/ml; Wilcoxon matched pair test, p=0.027). All patients had hyperprolactinemia (30-200 ng/ml). The prolactinemia was significantly higher in females (mean 160+/-50 ng/ml; median 198 ng/ml) than in males (mean 48+/-12 ng/ml; median 48 ng/ml; Mann-Whitney U test, p=0.041). CONCLUSION: Even low doses of amisulpride used as an augmentation to antidepressant treatment, benzodiazepines or in monotherapy seem to be associated with hyperprolactinemia. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia.
- MeSH
- amisulprid MeSH
- antidepresiva aplikace a dávkování MeSH
- antipsychotika aplikace a dávkování škodlivé účinky MeSH
- anxiolytika aplikace a dávkování MeSH
- deprese farmakoterapie MeSH
- dospělí MeSH
- hyperprolaktinemie krev chemicky indukované MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prolaktin krev MeSH
- sulpirid aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amisulprid MeSH
- antidepresiva MeSH
- antipsychotika MeSH
- anxiolytika MeSH
- prolaktin MeSH
- sulpirid MeSH
1. In a group of schizophrenic patients, the effect and selected parameters of biological markers were evaluated during the index hospitalisation in the acute phase of schizophrenia (n = 30) and then after one year of ambulatory treatment. 2. During the acute treatment, a significant drop in symptomatology was recorded in average; an analogical tendency was observed further on, too. Apart from that, a significant change was observed in 5/41 parameters being monitored (the pair t-test): I) decrease in the total NES score, II) decrease in the sensorial integration subscale NES score, III) increase in psychomotor speed, IV) decrease in auditory reaction time, V) increase in basal cortisol. 3. In the comparison of the successfully (severity of illness after one year = 1, 2) and unsuccessfully (severity of illness after one year > or =3) treated patients in the beginning of treatment in the acute phase, the unsuccessful group had a significantly higher score of negative symptomatology, and by the end of the acute treatment, again, a significantly higher score of negative symptomatology, a higher total PANSS score and a greater severity of illness. 4. In the acute phase, the successful group had a significantly better score in individual items of the Contemporary Memory Scale and a significantly worse performance and goal-aimed concentration in the Bourdon test than the unsuccessfully treated one; apart from that, it had a significantly higher cortisol level after dexamethasone, which was also reflected in the lower percentage rate of dexamethasone nonsupression. 5. In the course of the year, a drop in the total NES score for the individual subscales occurred; a significant drop was observed in the sensory integration subscale. The worse concentration items improved significantly in the successful group in contrast to the unsuccessful group, where they showed a downgrade tendency. Changes in Contemporary Memory Scale were negligible and mostly below statistical significance. Apart from that, a drop in basal cortisolemia occurred in the successful group and an increase in cortisolemia after administering dexamethasone was registered in the unsuccessful group. 6. The more successful group had a significantly lower NES score, a significantly better visual reaction time and a smaller forgetting item (in percentiles) after the one-year period.
- MeSH
- akutní nemoc MeSH
- amisulprid MeSH
- antipsychotika terapeutické užití MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dexamethason MeSH
- dospělí MeSH
- haloperidol terapeutické užití MeSH
- hospitalizovaní pacienti MeSH
- hydrokortison krev MeSH
- kognice MeSH
- lidé MeSH
- mozek diagnostické zobrazování MeSH
- následné studie MeSH
- paměť MeSH
- perfenazin terapeutické užití MeSH
- počítačová rentgenová tomografie MeSH
- psychologické testy MeSH
- psychomotorický výkon MeSH
- reakční čas MeSH
- schizofrenie (psychologie) * MeSH
- schizofrenie krev farmakoterapie patofyziologie MeSH
- sulpirid analogy a deriváty terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- amisulprid MeSH
- antipsychotika MeSH
- biologické markery MeSH
- dexamethason MeSH
- haloperidol MeSH
- hydrokortison MeSH
- perfenazin MeSH
- sulpirid MeSH