quetiapine-fumarate and perospirone

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dopamine Antagonists; Humans; Indoles; Isoindoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin Antagonists; Thiazoles

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dystonia; Humans; Indoles; Isoindoles; Parkinsonian Disorders; Quetiapine Fumarate; Receptors, Muscarinic; Receptors, Serotonin; Risperidone; Serotonin Antagonists; Syndrome; Thiazoles

Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle).. We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle.. Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands.. Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1.. The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Over Studies; Dibenzothiazepines; Electroencephalography; Fourier Analysis; Haloperidol; Humans; Indoles; Isoindoles; Male; Olanzapine; Quetiapine Fumarate; Reference Values; Risperidone; Single-Blind Method; Thiazoles; Time Factors

The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia.. Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology.. The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline.. These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Indoles; Isoindoles; Male; Middle Aged; Olanzapine; Polysomnography; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Sleep Stages; Thiazoles

To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia.. Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS).. Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS.. These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Health Status; Hospitalization; Humans; Indoles; Isoindoles; Japan; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Regression Analysis; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sleep; Thiazoles

The effect of drugs in the central nervous system (CNS) is closely related to occupancy of their target receptor. In this study, we integrated plasma concentrations, in vitro/in vivo data for receptor or protein binding, and in silico data, using a physiologically based pharmacokinetic model, to examine the predictability of receptor occupancy in humans. The occupancy of the dopamine D2 receptor and the plasma concentrations of the antipsychotic drugs quetiapine and perospirone in humans were collected from the literature or produced experimentally. Association and dissociation rate constants and unbound fractions in the serum and brain were determined in vitro/in vivo using human D2 receptor-expressing membrane fractions, human serum and mouse brain. The permeability of drugs across the blood-brain barrier was estimated based on their physicochemical properties. The effect of a metabolite of perospirone, ID-15036, was also considered. The time profiles of D2 receptor occupancy following oral dose of quetiapine and perospirone predicted were similar to the observed values. This approach could assist in the design of clinical studies for drug development and the prediction of the impact of drug-drug interactions on CNS function in clinical settings.

Topics: Adult; Animals; Antipsychotic Agents; Brain; Computer Simulation; Dopamine D2 Receptor Antagonists; Humans; Isoindoles; Kinetics; Male; Mice, Inbred ICR; Positron-Emission Tomography; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Thiazoles; Young Adult

An accumulating body of evidences point to the significance of neuroinflammation and immunogenetics in schizophrenia, characterized by increased serum concentration of several pro-inflammatory cytokines. In the central nervous system (CNS), the microglial cells are the major immunocompetent cells which release pro-inflammatory cytokines, nitric oxide (NO) and reactive oxygen species to mediate the inflammatory process. In the present study, we investigated whether or not atypical antipsychotics, namely perospirone, quetiapine and ziprasidone, would have anti-inflammatory effects on the activated microglia which may potentiate neuroprotection. All three atypical antipsychotics significantly inhibited NO generation from activated microglia while perospirone and quetiapine significantly inhibited the TNF-alpha release from activated microglia. Antipsychotics, especially perospirone and quetiapine may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

Topics: Animals; Antipsychotic Agents; Cell Survival; Cells, Cultured; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Interferon-gamma; Isoindoles; Mice; Mice, Inbred C57BL; Microglia; Nitrites; Piperazines; Quetiapine Fumarate; Rats; Tetrazolium Salts; Thiazoles

The ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) method has been developed to perform the determination of quetiapine, perospirone, aripiprazole and quetiapine sulfoxide in in vitro samples in less than 3 min. The UPLC separation was carried out using an Acquity UPLC BEH C18 column (100 mm x 2.1mm i.d., 1.7 microm particle size) that provided high efficiency and resolution in combination with high linear velocities. The UPLC system was coupled to a Waters Micromass Quattro Premier XE tandem quadrupole mass spectrometer. This system permits high-speed data acquisition without peak intensity degradation, and produces sharp and narrow chromatographic peaks (w(h) about 2.5s) of compounds. The determination was performed in multiple reaction monitoring (MRM) mode. The quantification parameters of the developed method were established, obtaining instrumental LODs lower than 0.005 microg/l and a repeatability at a low concentration level lower than 10% CV (n=10). Finally, the method was successfully applied to the analysis of atypical antipsychotics and some metabolites in in vitro samples.

Topics: Antipsychotic Agents; Aripiprazole; Chromatography, High Pressure Liquid; Dibenzothiazepines; Indoles; Isoindoles; Piperazines; Quetiapine Fumarate; Quinolones; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Thiazoles

The neural cell adhesion molecule (N-CAM) plays important roles in neural migration, synaptogenesis and CNS development. Change of N-CAM fragments in CSF of schizophrenic patients was reported previously, and we aimed to detect difference in circulating N-CAM in the serum of schizophrenic patients and healthy controls.. Samples were from 14 chronic schizophrenic patients including 3 drug naïve patients and 11 healthy controls. After removal of albumin and globulin, N-CAM fragments were measured by Western blot technique with monoclonal antibody.. N-CAM immunoreactive bands were detected primarily at 180, 140, 120, 75, 68 and 52 kDa. Samples from patients and controls showed similar patterns of bands, but schizophrenic patients showed increases or decreases at some bands intensity compared to healthy controls. The 68 kDa/73-75 kDa bands intensity ratio was substantially elevated in schizophrenic patients (0.262+/-0.14 in patients, 0.065+/-0.04 in controls) especially, the three drug naïve patients had a higher value of this ratio compared to the medicated patients. One drug naïve patient showed a decrease in this ratio after one month of antipsychotic medication.. The results suggest elevated membrane turnover and/or abnormalities in the regulation of proteolysis of N-CAM in schizophrenia.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Blotting, Western; Chronic Disease; Dibenzothiazepines; Female; Humans; Indoles; Isoindoles; Male; Middle Aged; Molecular Weight; Neural Cell Adhesion Molecules; Olanzapine; Protein Isoforms; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles