BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy

Bipolar disorder is a chronic, recurrent condition with the usual onset during adolescence or early adulthood. In the Diagnostic and Statistical Manual of Mental Disorders 5th edition, it is conceptualized as a spectrum disorder usually associated with such comorbidities as anxiety disorders and substance use disorders. It is a relatively prevalent condition often complicated by mixed episodes, rapid cycling, subsyndromal symptoms, and treatment refractoriness. In spite of carrying substantial morbidity and mortality, effective treatments are few and far between and conventional mood stabilizers are often unsuccessful in controlling the various manifestations of the disorder. In this scenario, second generation antipsychotics are emerging as treatments with valid efficacy in all phases of bipolar disorder. Quetiapine is a versatile atypical antipsychotic which was first approved for the treatment of schizophrenia, but latter on the basis of controlled studies earned United States Food and Drug Administration's approval for acute as well as maintenance treatment of this difficult to treat condition. In this review, recently published studies in the last 10 years were examined to update the knowledge about the efficacy and safety of quetiapine in the treatment of bipolar disorder. The medication's clinical pharmacology was first considered followed by a literature review summarizing its uses in bipolar disorder. The conclusion was that quetiapine was efficacious in manic, mixed and depressive episodes and as a maintenance agent with a good tolerability profile.
Adolescent ; Antipsychotic Agents ; Anxiety Disorders ; Bipolar Disorder* ; Comorbidity ; Diagnostic and Statistical Manual of Mental Disorders ; Drug Therapy* ; Humans ; Mortality ; Pharmacology, Clinical ; Schizophrenia ; Substance-Related Disorders ; United States ; Quetiapine Fumarate

OBJECTIVETo investigate the effect of risperidone, an antipsychotic drug, on the Akt-GSK3β pathway and the role of PI3K in dopamine D2 receptor (DRD2) expression and Akt-GSK3β signal pathway.

METHODSHuman glioma cells (U251) were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt (Thr308 and Ser473) and GSK3β (Ser9) protein phosphorylation by risperidone and LY294002 in U251 cell, and real-time PCR was used for detecting the expression of DRD2 mRNA.

RESULTSRisperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β (P< 0.05), but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK3β (P< 0.01, P< 0.05), and also decrease the DRD2 mRNA (P<0 .05).

CONCLUSIONRisperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.

Antipsychotic Agents ; pharmacology ; Cell Line, Tumor ; Glioma ; drug therapy ; genetics ; metabolism ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Risperidone ; pharmacology ; Signal Transduction ; drug effects

Human-induced pluripotent stem cells (hiPSCs) derived from somatic cells of patients have opened possibilities for in vitro modeling of the physiology of neural (and other) cells in psychiatric disease states. Issues in early stages of technology development include (1) establishing a library of cells from adequately phenotyped patients, (2) streamlining laborious, costly hiPSC derivation and characterization, (3) assessing whether mutations or other alterations introduced by reprogramming confound interpretation, (4) developing efficient differentiation strategies to relevant cell types, (5) identifying discernible cellular phenotypes meaningful for cyclic, stress induced or relapsing-remitting diseases, (6) converting phenotypes to screening assays suitable for genome-wide mechanistic studies or large collection compound testing and (7) controlling for variability in relation to disease specificity amidst low sample numbers. Coordination of material for reprogramming from patients well-characterized clinically, genetically and with neuroimaging are beginning, and initial studies have begun to identify cellular phenotypes. Finally, several psychiatric drugs have been found to alter reprogramming efficiency in vitro, suggesting further complexity in applying hiPSCs to psychiatric diseases or that some drugs influence neural differentiation moreso than generally recognized. Despite these challenges, studies utilizing hiPSCs may eventually serve to fill essential niches in the translational pipeline for the discovery of new therapeutics.
Animals ; Antipsychotic Agents/pharmacology ; *Drug Discovery ; Humans ; Induced Pluripotent Stem Cells/cytology/*drug effects/metabolism ; Mental Disorders/*drug therapy/metabolism ; *Nuclear Reprogramming

Schizophrenia, described as the worst disease affecting mankind, is a severe and disabling mental disorder. Schizophrenia is characterized by complicated symptoms and still lacks a diagnostic neuropathology, so developing schizophrenia animal models which have quantifiable measures tested in a similar fashion in both humans and animals will play a key role in new therapeutic approaches. According to the symptoms of cognitive impairment and emotional disorder, the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 was applied to induce schizophrenia-like behavior in mice. Locomotor activity and prepulse inhibition (PPI) were selected as indices and the effect of clozapine was also investigated in this model. The results showed that compared with the normal group, MK-801-treated mice exhibited significantly increased locomotor activity and impaired PPI, and pre-exposure to clozapine could ameliorate the abnormality and make it back to normal level. These findings suggest that the model we established could be a useful tool for antipsychotic drug screening.
Animals ; Antipsychotic Agents ; pharmacology ; Clozapine ; pharmacology ; Disease Models, Animal ; Dizocilpine Maleate ; Inhibition (Psychology) ; Male ; Mice ; Motor Activity ; drug effects ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; Schizophrenia ; chemically induced ; physiopathology

OBJECTIVETo observe the effect of traditional Chinese medicine storax on the concentration of combined western medicine sulpiride in brain and blood, discuss the effect of storax in inducing resuscitation and increasing the permeability of the gastrointestinal barrier (GB) and the blood-brain-barrier (BBB), and explore the interaction between storax and sulpiride.

METHODRats were orally administered with the drugs for one week, probes were implanted in their brains and necks by surgery. After balance for 60 min, brain microdialysis and blood microdialysis were adopted for collect dislysates from blood in right atrum and cerebral hippocampus at time periods of 30, 60, 90, 120, 150, 180 min. The concentration of sulpirde in the samples was detected by RP-HPLC. Statistical approaches were adopted to compare the contents of sulpirde in brain and blood of the two groups.

RESULTThe sulpiride combined with storax group showed a significant higher concentration of sulpiride than the pure sulpiride group. The pure sulpiride group showed a concentration ratio between sulpiride in brain and blood of 1:0.2; while the sulpiride combined with storax group increased the concentration ratio between sulpiride in brain and blood to 1:0.3. Compared with the pure sulpiride group, the sulpiride combined with storax group showed an increase of concentration by 39% in brain and 69% in blood.

CONCLUSIONStorax can notably increase the concentration of sulpiride in rat brain and blood, indicating that it can increase the permeation of sulpiride through gastrointestinal barrier and BBB. This study reveals the mechanism of storax in inducing resuscitation by promoting the permeation through gastrointestinal barrier and BBB.

Animals ; Antipsychotic Agents ; pharmacokinetics ; Blood-Brain Barrier ; drug effects ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Sulpiride ; pharmacokinetics

INTRODUCTIONThis study aimed to compare the effects of the two most commonly prescribed atypical antipsychotics, olanzapine and risperidone, on fasting blood sugar and serum lipid profile of the recipients.

METHODSA randomised, comparative, open clinical study was conducted on 60 schizophrenic patients. The patients were divided into two groups, one receiving olanzapine and the other receiving risperidone. The patients were assessed for changes in fasting blood sugar and serum lipid profile (triglycerides [TG], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL] and total cholesterol) eight weeks after starting treatment. The number of patients positive for fasting blood sugar and lipid profile criteria of metabolic syndrome was calculated by applying the modified National Cholesterol Education Programme Adult Treatment Panel III guidelines (NCEP ATP III) criteria at eight weeks.

RESULTSPatients treated with olanzapine showed a highly significant increase in the observed parameters, whereas those treated with risperidone showed a significant increase in fasting blood sugar, HDL and LDL levels, and a highly significant increase in other parameters. Intergroup comparison was insignificant except for TG, VLDL and total cholesterol levels. More men as compared to women fulfilled the NCEP ATP III criteria for metabolic syndrome in both groups.

CONCLUSIONOlanzapine has a higher propensity to cause derangement of some parameters of lipid profile than risperidone. These parameters include TG, VLDL and total cholesterol levels.

Adolescent ; Adult ; Antipsychotic Agents ; pharmacology ; Benzodiazepines ; pharmacology ; Blood Glucose ; drug effects ; Cholesterol ; blood ; Female ; Humans ; Lipids ; blood ; Lipoproteins, HDL ; drug effects ; Lipoproteins, LDL ; blood ; Lipoproteins, VLDL ; drug effects ; Male ; Metabolic Syndrome ; complications ; diagnosis ; Reproducibility of Results ; Risperidone ; pharmacology ; Schizophrenia ; blood ; drug therapy ; Triglycerides ; blood

OBJECTIVETo explore the effect of anti-psychotic treatment on the expression of Neuregulin-1 (NRG1) mRNA in the peripheral blood lymphocytes of schizophrenia patients.

METHODSThe NRG1 mRNA in peripheral blood lymphocytes was measured using semi-quantitative reverse transcription (RT)-PCR in 80 first-onset schizophrenia patients, 37 sibling controls and 83 non-related controls. The patients were treated with risperdone and quetiapine for 4 weeks. Positive and negative symptom scale (PANSS) was used to evaluate the severity and clinical efficacy.

RESULTSPrior to the treatment, the expression of NRG1 mRNA expression was significantly lower in patients than other two groups (F=73.004, P=0.000). From the second week on, the level of NRG1 mRNA expression in patients became significantly higher than before and gradually increased, whilst no significant difference between sib and non-sib controls. Prior to the treatment, there was significant correlation (r=-0.232, P=0.038) between the level of NRG1 mRNA and PANSS scores. Four weeks after the treatment, a significant correlation between the reduction rate of PANSS and the change of NRG1 mRNA (r=0.27, P=0.016).

CONCLUSIONThe expression of NRG1 gene mRNA is associated with schizophrenia. Decreased expression of NRG1 may play a role in the development of schizophrenia, which can be improved by anti-psychotic drugs.

Adolescent ; Adult ; Antipsychotic Agents ; pharmacology ; therapeutic use ; Female ; Gene Expression ; drug effects ; Gene Expression Regulation ; drug effects ; Humans ; Male ; Neuregulin-1 ; genetics ; RNA, Messenger ; metabolism ; Schizophrenia ; drug therapy ; genetics ; Time Factors ; Young Adult

Psychopharmacology has developed over approximately the past five decades. The remarkable proliferation of information in this area has made it difficult for clinicians to understand the characteristics of various psychotropic agents. Atypical antipsychotics including amisulpride, asenapine, aripiprazole, blonanserin, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and zotepine cause fewer extrapyramidal problems and have many clinical applications, but they can cause metabolic disturbances. Mood stabilizers and lamotrigine are widely used for bipolar disorder. Other novel anticonvulsants such as topiramate, oxcarbazepine, gabapentin, tiagabine, pregabalin, vigabatrin, levetiracetam, and riulzole have also been tested with diverging or inconclusive results. Antidepressants are commonly used in the clinical treatment of depression and anxiety disorder. However, the mechanism of action of medications used in the treatment of psychiatric disorders remains unclear. Understanding the mechanisms of action and clarifying the diagnosis may enhance the treatment outcome in psychiatry. In this review, we analyzed clinical pharmacology data for each drug within a class and discussed clinical strategies for administering currently available antipsychotics, mood stabilizer/anticonvulsants, and antidepressants widely used for various psychiatric indications.
Aripiprazole ; Amines ; Anticonvulsants ; Antidepressive Agents ; Antipsychotic Agents ; Anxiety Disorders ; Benzodiazepines ; Bipolar Disorder ; Carbamazepine ; Clozapine ; Cyclohexanecarboxylic Acids ; Depression ; Dibenzothiazepines ; Dibenzothiepins ; Fructose ; gamma-Aminobutyric Acid ; Heterocyclic Compounds with 4 or More Rings ; Lurasidone Hydrochloride ; Isoindoles ; Isoxazoles ; Nipecotic Acids ; Quetiapine Fumarate ; Pharmacology, Clinical ; Pregabalin ; Piperazines ; Piperidines ; Piracetam ; Psychopharmacology ; Pyrimidines ; Quinolones ; Risperidone ; Sulpiride ; Thiazoles ; Treatment Outcome ; Triazines ; Vigabatrin

This study aimed to investigate the transport characteristics of aripiprazole. A human intestinal epithelial cell model Caco-2 cell in vitro cultured had been applied to study the transport of aripiprazole. The effects of time, concentration of donor solutions, pH, temperature and P-glycoprotein inhibitor on the transport of aripiprazole were investigated. The determination of aripiprazole was performed by HPLC. It is concluded that aripiprazole is transported through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport. The transport of aripiprazole is positively correlated to transport time, pH, and temperature. Papp increased with donor concentrations up to 10 microg x mL(-1), and then decreased for higher concentrations. The P-glycoprotein inhibitor cyclosporine A significantly enhanced the transport amount of aripiprazole.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Antipsychotic Agents ; administration & dosage ; pharmacokinetics ; Aripiprazole ; Biological Transport ; drug effects ; Caco-2 Cells ; Cyclosporine ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Hydrogen-Ion Concentration ; Piperazines ; administration & dosage ; pharmacokinetics ; Quinolones ; administration & dosage ; pharmacokinetics ; Temperature ; Time Factors