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On the mechanisms of action of atypical antipsychotic drugs : an experimental study /Hertel, Peter, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.
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Influence of antipsychotic drugs on hormone levels /Melkersson, Kristina, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.
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Neuroleptic-induced persistent dyskinesia behavioural and biochemical studies /Häggström, Jan-Erik. January 1984 (has links)
Thesis (doctoral)--University of Uppsala, 1984. / Bibliography: p. 33-45.
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Pharmacokinetic studies of fluphenazine and four ester prodrugsLuo, Jiang Ping 01 January 1999 (has links)
The purpose of present thesis work was to investigate the pharmacokinetics of FLU and four aliphatic esters, FLU-A, FLU-B, FLU-E and FLU-D, and in particular, the impact of the ester groups on the pharmacokinetics of the parent compound FLU after administration of the prodrugs in oil based injections. It was determined that the sesame oil/buffer partition coefficients (PC) decreased as the homogenous series of the ester chain length was increased, the effect of the chain length of the prodrug on the release rate of the corresponding prodrug from the oily depot. Furthermore, the results from 'in vitro ' enzymatic experiments using plasma, liver and muscle homogenates obtained from dog or human showed that lipophilicity of the esters predominated over other parameters such as enzymatic hydrolysis in determining the sustained production of FLU when the prodrugs were given as oil based intramuscular depot formulations. The roles of depot injection sites and proximal lymph nodes in the absorption kinetics of FLUand prodrug were investigated by intramuscular administration of either FLU base or FLU-D in sesame oil to groups of rats. The quantitative data suggested the involvement of the lymphatic system in the presystemic absorption of FLU and FLU-D after intramuscular administration of FLU-D in sesame oil. Finally, intravenous or intramuscular pharmacokinetics of FLU and four esters were investigated in dogs. The results showed that the chain length affected the kinetics of both FLU and the ester prodrugs. A pharmacokinetic model (s) was developed to simulate the disposition of FLU-D and the formation of FLU after either intravenous or intramuscular administration of FLU-D. Satisfactory fits of the simulated profiles with the observed data implies that the prolonged elimination profiles of FLU observed after intravenous administration could be rate limited by the ester chain length dependent distribution or redistribution of the prodrug from poorly perfused (fatty) deep compartments and subsequent hydrolysis in more highly perfused tissues while the ultimate rate limiting step in the absorption kinetics of FLU and prodrug after intramuscular administration could be the slow partitioning out of prodrug from the oily deposits at the injection sites and surrounding tissues such as proximal lymph nodes with the subsequent hydrolysis of the ester group in the body.
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Depot neuroleptic maintenance treatment clinical, pharmacological and neuropsychological aspects /Tuninger, Eva. January 1997 (has links)
Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.
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Depot neuroleptic maintenance treatment clinical, pharmacological and neuropsychological aspects /Tuninger, Eva. January 1997 (has links)
Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.
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The effects of dose and duration of neuroleptic administration on dopamine receptor sensitivityDewey, Kevin John January 1981 (has links)
It is well established that chronic treatment with neuroleptic agents which selectively block dopamine (DA) receptors in the brain leads to the development of DA receptor supersensitivity. However comparing the degree and duration of the changes in receptor sensitivity obtained by different investigators has been extremely difficult, because of the numerous differences that exist in individual methods of producing and examining DA receptor supersensitivity. By examining the DA receptor supersensitivity that ensues following chronic treatment with different doses and durations of pimozide, at various intervals after withdrawal from treatment, the overall parametric changes can be more directly compared. To measure the changes in DA receptor sensitivity following chronic pimozide treatment, both behavioral (d.-amphetamine-induced locomotor activity; apomorphine-induced stereotypy) and biochemical (DA receptor binding assay) techniques were utilized. With increasing doses of chronic pimozide treatment, the degree and duration of the resulting DA receptor supersensitivity increased as measured both behaviorally and biochemically. Similarily, the longer durations of chronic pimozide treatment had a greater effect on the degree and duration of the increased DA receptor sensitivity than did the shorter durations of treatment. Correlations were found between the biochemical and behavioral results both between groups of animals treated chronically with different doses and durations of pimozide and within individual groups of animals. In addition, the changes in receptor sensitivity following chronic pimozide treatment was due to an increase in the number of DA receptors with no change in the affinity of these receptors to DA.
These results following chronic treatment with neuroleptics demonstrate that the behavioral supersensitivity observed in animals in response to either the direct DA agonist apomorphine or the indirect DA agonist d-amphetamine, may be a result of an increased number of DA receptors. Finally, the supersensitive DA receptors that develop as a result of chronic treatment with neuroleptics are discussed with regard to their possible relevance as an animal model of the iatrogenic disease, tardive dyskinesia, observed clinically in schizophrenic patients withdrawn from neuroleptic therapy. / Medicine, Faculty of / Graduate
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Eficácia de antipsicóticos atípicos comparados à clozapina em pacientes com esquizofrenia refratária: revisão sistemática e metanálise / Efficacy of atypical antipsychotics versus clozapine in patients with refractory schizophrenia: systematic review and meta-analysisSouza, Juliano dos Santos 06 October 2010 (has links)
INTRODUÇÃO: Considera-se a clozapina como padrão-ouro para o tratamento de pacientes com esquizofrenia refratária, com base principalmente em sua eficácia comprovadamente superior em relação aos antipsicóticos típicos. No entanto, os dados acerca do uso de outros antipsicóticos atípicos ainda são escassos ou divergentes. Tendo em vista que o uso de clozapina está associado a várias limitações, existe uma necessidade não atendida de alternativas terapêuticas eficazes e seguras para a esquizofrenia refratária. MÉTODOS: Foi realizada uma revisão sistemática de estudos controlados e randomizados (ECRs), comparando clozapina aos outros antipsicóticos atípicos, em pacientes com esquizofrenia refratária. Foram realizadas metanálises avaliando a eficácia das intervenções, medida por meio de escalas de avaliação de sintomas psicóticos. A resposta ao tratamento foi medida por meio da porcentagem de respondedores ou pela mudança média ou valores finais dos escores das escalas. Quando possível, foram realizadas metanálises da comparação entre clozapina e outro antipsicótico atípico específico. Os tamanhos de efeito foram dados pelo risco relativo (RR) ou pela diferença entre médias (DM), ponderada ou padronizada, acompanhados dos respectivos intervalos de confiança de 95%. As metanálises foram realizadas utilizando-se o modelo de efeitos fixos, ou aleatórios, no caso de haver heterogeneidade entre os estudos. Foram realizadas análises de sensibilidade, excluindo-se estudos que haviam incluído pacientes intolerantes junto à população refratária. RESULTADOS: Onze ECRs foram incluídos, representando 1182 pacientes, com 12 comparações entre clozapina e antipsicóticos atípicos: quatro com risperidona, um com ziprasidona e sete com olanzapina. Considerados como um grupo, não foi possível determinar diferenças no tamanho de efeito entre a clozapina e os outros antipsicóticos atípicos em nenhum tipo de medida geral de sintomas psicóticos. A metanálise que combinou as mudanças médias e os valores finais da PANSS e da BPRS apresentou uma diferença de médias de 0,00 (IC95%= -0,12, 011). Foi observada superioridade marginal dos antipsicóticos atípicos para sintomas negativos, medidos pelos valores finais da PANSS (DM= -1,96, IC95%= -3,44, -0,48). Foi observado que os estudos que compararam a clozapina à olanzapina tiveram doses finais médias altas de olanzapina (médias de 17,2 mg/d a 33,6 mg/d), o que pode ter influenciado nos resultados.CONCLUSÕES: Os antipsicóticos atípicos, particularmente a olanzapina em doses altas, podem representar uma alternativa de tratamento para pacientes com esquizofrenia refratária / BACKGROUND: Clozapine is considered as the gold standard for the treatment of patients with refractory schizophrenia, based upon its well established superior efficacy against typical antipsychotics. Nevertheless, data on other atypical antipsychotics are still scarce or divergent for this population. Considering that clozapine use is associated to several caveats, there is an unmet need for safe and efficacious alternative therapeutic approaches for refractory schizophrenia. METHODS: It was conducted a systematic review of randomized clinical trials (RCTs) comparing clozapine to other atypical antipsychotics in patients with refractory schizophrenia. Metanalyses assessing the efficacy of interventions were performed. Efficacy was measured by psychotic symptoms scales. Response to treatment was measured by the percentage of responders or by mean change or endpoints values of such scales. Whenever possible, metanalyses comparing clozapine to other specific atypical antipsychotic were performed. Effect sizes were shown as relative risks (RR) or weighted or standardized mean differences (MD), with 95% confidence intervals. The fixed effect model was used, unless studies were considered heterogeneous. Sensivity analyses were performed with the exclusion of studies which had included intolerant patients along with true refractory patients. RESULTS: Eleven RCTs were included, figuring 1182 patients, with 12 comparisons between clozapine and other atypical antipsychotics: four with risperidone, one with ziprasidone, and seven with olanzapine. Considered as a group, it was not possible to determine different effect sizes between atypical antipsychotics and clozapine for any general measure of psychotic symptoms. Pooled mean change and endpoint PANSS and BPRS scores metanalysis presented a zero mean difference (MD=0.00, CI95%= -0.12, 0.11). Atypical antipsychotics were shown to be marginally superior to clozapine for negative symptoms, measured by PANSS negative symptoms subscale endpoint scores (DM= 1.96, CI95%= -3.44, -0.48). Studies which compared clozapine to olanzapine had relatively high mean final olanzapine doses (means ranging from 17.2 mg/d to 33.6 mg/d), what might have influenced the results. CONCLUSIONS: Atypical antipsychotics, particularly high dose olanzapine, can represent an alternative therapeutic approach to patients with refractory schizophrenia
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Novel mechanism of action of antipsychotic drugs : effects on neuropeptides in rat brain /Gruber, Susanne H. M., January 2002 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.
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Regulation of signal transduction in the striatum by typical and atypical antipsychotic drugs /Håkansson, Kerstin, January 2005 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.
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