Atypical antipsychotics have more beneficial effects than conventional antipsychotics, particularly with regard to negative symptoms, cognitive functions, and also have a superior side effect profile. Although with such advantages, the use of the atypical antipsychotics cause numerous complications such as hypertension, increase of insuline, diabetes mellitus due to gain in weight, hyperprolactinemia, sexual dysfunctions, cardiovascular symptoms as well as noncompliance due to the previously mentioned side effects and high medical expenses which burden individual and governments. Now is the time to consider both advantages and disadvantages to balance out gains and losses in using the atypical antipsychotics. Blind trust or exclusive decision in using the atypical antipsychotics are unsuitableness. The decision on the use of the medicine must be the one that balances out its general advantages and disadvantages and its appropriateness must be decided upon a full consideration of its pharmacology, efficacies and side effects.
Antipsychotic Agents* ; Diabetes Mellitus ; Hyperprolactinemia ; Hypertension ; Insulin ; Neurobehavioral Manifestations ; Pharmacology

OBJECTIVE: This study was performed to investigate the prescribing patterns of antimanic agents in the treatment of acute bipolar disorder inpatients in Korea from 1990 through 2000. The results will serve as the basic data for the practice guideline for the pharmacotherapy of bipolar disorder patients in Korea. METHOD: Retrospective chart review of bipolar disorder inpatients of Soonchunhyang Medical Center in Seoul and Chun-An was conducted for each of the year 1990, 1995, and 2000. The following data are collected ; 1) demographic data, 2) history of bipolar disorder, 3) length of hospital stay, 4) detailed drug titration records of antimanic agents and antipsychotic agents. RESULTS: During the last decade, the frequency of lithium monotherapy was decreased obviously. Instead, more than half of the patients in 2000 were on combination therapy of lithium and anticonvulsants. Lithiumvalproate combination was the preferred strategy and the use rate of carbamazepine has been decreased. In addition, most of the patients were given antipsychotic agents during the last 10 years. And recently, atypical antipsychotics were increasingly prescribed. These changes in the field of pharmacology of bipolar disorder have resulted neither in shorter hospital stays nor lower dosages of concurrent neuroleptics. CONCLUSIONS: The results indicate the trends in the prescribing of antimanic agents for the treatment of bipolar disorder in Korea across the past 10 years. Mostly, the change seems to correspond to the international practice guideline. More systematic research is needed to find out the clinical benefits of the anticonvulsants in the real practice of treatment of bipolar disorder.
Anticonvulsants ; Antimanic Agents* ; Antipsychotic Agents ; Bipolar Disorder ; Carbamazepine ; Drug Therapy ; Humans ; Inpatients* ; Korea ; Length of Stay ; Lithium ; Pharmacology ; Retrospective Studies ; Seoul

A series of nitrogen-containing benzoheterocyclic derivatives were synthesized and tested for their antipsychotic activities. Their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological trials showed that most of the target compounds have high affinity with D2 and 5-HT(2A) receptors. Among the tested compounds, 20 exhibited the highest affinity and D2 partial agonist activity. In vivo studies showed 20 has potent antipsychotic activities on apomorphine mice model, which is a chance to find a better precursor of D2 partial agonist for further optimization.
Animals ; Antipsychotic Agents ; chemical synthesis ; pharmacology ; Dopamine Agonists ; chemical synthesis ; pharmacology ; Drug Design ; Isoquinolines ; chemical synthesis ; pharmacology ; Mice ; Receptors, Dopamine D2 ; Structure-Activity Relationship

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

This paper reviews history of new drug development in Korea as well as researchs on development of new psychotherapeutic drug from traditional medicines or natural products in Korea. Korea has a long history of traditional medicine and accumulated knowledge of natural resources. However, only a few new drug have been developed from those natural products. Now many researchers in Korea are devoting themselves to test the possibility of natural products as antipsychotic drugs, antidepressants, anxiolytic drugs and cognitive enhancers. However, only a few graduates from traditional medical schools in Korea are engaging in research on developing new drug from natural products and they are not familiar to research methods of western medicine and pharmacology. For research and development of new drug from natural products or traditional medicines, many researchers should be trained for methodology of basic medicine, pharmacology, pharmacognosy, and oriential pharmacy. Government and pharmaceutical companies need to provide more investment for R & D for new drug from natural products including establishment of data base for component of traditional medicines and natural products, system development integrating information technology, bio-technology and nanotechnology, and international collaboration with advanced countries which have common interest in new drug development from natural products.
Antidepressive Agents ; Antipsychotic Agents ; Biological Products ; Natural Resources ; Cooperative Behavior ; Investments ; Korea ; Medicine, Korean Traditional ; Medicine, Traditional ; Nanotechnology ; Nootropic Agents ; Pharmacognosy ; Pharmacology ; Pharmacy ; Schools, Medical

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

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

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

Glycogen synthase kinase 3 (GSK3) was recently suggested to be a potential target of psychotropics used in psychiatric illnesses such as schizophrenia and bipolar disorder. Relevant studies have found that antipsychotic drugs regulate GSK3 activity via an increase in either inhibitory serine phosphorylation or amount of GSK3 after acute or subchronic treatment. Recent evidence shows that GSK3 is regulated by dopaminergic or serotonergic systems implicated in the pathophysiology and treatment mechanisms of schizophrenia and bipolar disorder. Therefore, antipsychotics may regulate GSK3 via antagonizing dopaminergic or serotonergic activity. However, the signaling pathway that is involved in GSK3 regulation by dopaminergic or serotonergic systems has not been well established. Haloperidol is a typical antipsychotic with potent dopamine D(2) receptor antagonism. Clozapine is an atypical antipsychotic with potent serotonin 5HT(2) receptor antagonism. We injected rats with haloperidol or clozapine and examined the phosphorylation and amount of GSK3alpha/beta and its well-known upstream regulators Akt and Dvl in the rat frontal cortex by Western blotting. Both haloperidol and clozapine induced Ser21/9 phosphorylation of GSK3GSK3alpha/beta. Haloperidol increased the Ser473 phosphorylation of Akt transiently, whereas clozapine maintained the increase for 1 h. Haloperidol did not affect the phosphorylation and amount of Dvl, whereas clozapine increased both phosphorylation and the amount of Dvl. Our results suggest that GSK3 activity may be regulated by both typical and atypical antipsychotics and that Akt or Dvl, depending on the D(2)- or 5HT(2)- receptor antagonism properties of typical and atypical antipsychotics, mediate the regulation differently.
Adaptor Proteins, Signal Transducing/metabolism/*physiology ; Animals ; Antipsychotic Agents/*pharmacology ; Clozapine/*pharmacology ; Dopamine Antagonists/pharmacology ; Frontal Lobe/*drug effects/enzymology ; Glycogen Synthase Kinase 3/*metabolism ; Haloperidol/*pharmacology ; Male ; Phosphoproteins/metabolism/*physiology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism/*physiology ; Rats ; Rats, Sprague-Dawley ; Serotonin Antagonists/pharmacology ; Signal Transduction

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