OBJECTIVETo study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized (OBX) rats. Out of various derivatives tested for acute tail suspension test, the two derivatives showing prominent action were selected for bilateral olfactory bulbectomy model of chronic depression in rats.

METHODSThe sub acute effects of 14-day oral pretreatment of two derivatives labeled as 3a (70 mg/kg) and 3r (70 mg/kg), imipramine (20 mg/kg), fluoxetine (30 mg/kg) and moclobemide (15 mg/kg) were evaluated on bilateral bulbectomy induced rise in body weight, hyperphagia, hyperactivity, and on sexual dysfunction. The serum sodium concentration, body temperature, and heart rate were also recorded.

RESULTSThe derivatives 3a and 3r showed reversal of drop in body weight, reversed OBX induced hyperactivity, normalized body temperature, heart rate, and serum sodium concentration. In elevated maze test, moclobemide, 3a, 3r treatment significantly reduced time spent in open arm as compared to OBX rats. 3a and 3r also improved sexual behavior parameters.

CONCLUSIONSThe present study shows promising antidepressant action and provides a proof of concept for the chronic treatment of 3a, 3r to treat depression.

Acetamides ; pharmacology ; Acetanilides ; pharmacology ; Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; drug therapy ; etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Fluoxetine ; pharmacology ; Imipramine ; pharmacology ; Male ; Moclobemide ; pharmacology ; Olfaction Disorders ; complications ; pathology ; Olfactory Bulb ; surgery ; Rats ; Rats, Sprague-Dawley ; Triazines ; pharmacology

OBJECTIVE: With respect to the pharmacotherapy of social anxiety disorder (SAD), it has been suggested that treatment duration is an important factor that can significantly predict responses. The present study aimed to compare the treatment adherence of SAD patients who were taking either SSRIs or reversible inhibitors of MAO-A (moclobemide) by measuring treatment duration and all-cause discontinuation rates of pharmacotherapy in a natural clinical setting. METHODS: We retrospectively analysed the data of 172 patients diagnosed with SAD. Depending on their medication, we divided the patients into two groups, SSRI (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation every 2 weeks after starting treatment was calculated by life table survival methods. A multi-variable Cox proportional hazard regression was used to analyze the potential influence of explanatory variables. RESULTS: Treatment duration was significantly longer in the SSRI group [46.41+/-56.96, median=12.0 (weeks)] than in the moclobemide group [25.53+/-34.74, median=12.0 (weeks), Z=2.352, p=0.019]. Overall, all-cause discontinuation rates were significantly lower with SSRIs (81%) than moclobemide (96%, chi2=4.532, p=0.033). CONCLUSION: The SSRI group had a longer treatment duration and lower all-cause discontinuation rate than moclobemide. Further, only the type of medication had a significant effect on all-cause discontinuation rates and therefore, we could predict better treatment adherence with the SSRIs in the treatment of SAD.
Anxiety ; Anxiety Disorders ; Humans ; Life Tables ; Moclobemide ; Monoamine Oxidase ; Retrospective Studies ; Serotonin Uptake Inhibitors

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.
Acetylcholine ; Alzheimer Disease ; Antidepressive Agents ; Depression ; Freezing ; Handling (Psychology) ; Head ; Indans ; Iron ; Levodopa ; Moclobemide ; Monoamine Oxidase ; Monoamine Oxidase Inhibitors ; Parkinson Disease ; Phenelzine ; Selegiline ; Tranylcypromine

PURPOSE: We aimed to develop and validate a prediction model for the number of patients visiting emergency departments. METHODS: Enrolled patients were from eleven regional emergency departments (EDs) (level-1) that inputted information on emergency patients into the National Emergency Department Information System since 2004. We developed the automated regressive integrated moving average (ARIMA)-based prediction model using a dataset covering 2005 to 2007. To validate the prediction model, we performed Bland-Altman plot analysis for a new dataset, that of 2008, calculating the agreement rate. RESULTS: The total number of enrolled patients was 1,532,294. Of these, 844,802 (55.1%) were male and mean age was 36.5. The ARIMA (1, 1, 1) (1, 1, 1) 7 was selected as the best-fit prediction model. When we tested the validity using Bland-Altman plots, the agreement rate was 96.4% (95% CI, 94.0%~98.1%). Non-agreement dates were national holidays (n=9), and the other weekdays (n=4), respectively. CONCLUSION: We developed the ARIMA-based prediction model for emergency patients at regional EDs. The model showed a very high validity.
Chronology as Topic ; Emergencies ; Emergency Medical Services ; Holidays ; Humans ; Information Systems ; Male ; Moclobemide ; Models, Statistical ; Reproducibility of Results

OBJECTIVES: The diagnosis of depression is based on a highly variable set of symptoms. Therefore, depression should not be viewed as a single disease, but a heterogenous syndrome comprised of different pathophysiologies. There are several subtypes of depression which were already incorporated in DSM-IV. This article provides a systematic review of pharmacological treatments of two recognized subtypes of depression-dysthymic disorder and atypical depression. METHODS: Systematic search of relevant literatures on dysthymic disorder and atypical depression was performed by proposed search strategy of the Clinical Research Center for Depression of Korean Health 21 R&D Project. All identified literatures were carefully reviewed and classified according to SIGN grading system and summarized in a narrative manner. RESULT: For the treatment of dysthymic disorder and atypical depression, selective serotonin reuptake inhibitors(SSRIs) and moclobemide have more evidence than the other antidepressants. SSRIs and moclobemide showed superior tolerability than tricyclic antidepressants. CONCLUSION: The authors proposed treatment recommendations for dysthymic disorder and atypical depression by the methods of evidence-based medicine(EBM). However, guideline developing methods of EBM also have several inevitable limitations. Therefore, in the absence of clear and significant differences in efficacy, the choice of medication must be individualized for a particular patient based on psychiatrist's own clinical decision.
Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Depression* ; Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Dysthymic Disorder* ; Evidence-Based Medicine ; Humans ; Moclobemide ; Serotonin

OBJECTIVE: Although there are a few studies reporting the efficacy of moclobemide in the treatment of social phobia, it has been poorly studied in Korea. The purpose of this study was to investigate the short term efficacy of moclobemide in Korean patients with social phobia. METHOD: Sixty six patients with social phobia based on DSM-IV criteria were enrolled to 4-week trial with a flexible-dose regime of moclobemide. Treatment responses were assessed at baseline and week 4 with Liebowits Social Anxiety Scale (LSAS), Brief Fear of Negative Evaluation (BFNE), Mattick's Social Phobia Scale, Beck Depression Inventory (BDI), and Sheehan's Disability Scale (SDS). RESULT: Thirty eight of 66 patients completed the 4-week trial. Scores of LSAS, BFNE, and Mattick's Social Phobia Scale at baseline were not significantly reduced after 4-week trial (p=0.084, p=0.537, p=0.283, p=0.111, respectively). But scores of BDI and 3 of 4 Sheehan's Disability Subscale at baseline were significantly reduced (p=0.026, p=0.000, p=0.005, p=0.002, respectively). CONCLUSION: Overall results of preliminary study showed that moclobemide could be used for the treatment of depression and functional impairment, but that it was not effective for treatment of anxiety and phobic avoidance of social phobic patients. More controlled, long-term studies are needed to evaluate the efficacy of moclobemide for treatment of social phobia.
Anxiety ; Depression ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Korea ; Moclobemide* ; Phobic Disorders*

No abstract available.
Depression* ; Moclobemide*

OBJECTIVE: Amyloid beta protein(Abeta) has been regarded to be toxic to neurons in vitro. However, the mechanism of action leading to neuronal death remains unknown. In this study, we report the effects of psychotropic drugs, that are often prescribed for the improvement of psychotic and depressive symptoms in dementia of the Alzheimer's type, on the beta-amyloid-induced cytotoxicity in rat pheochromocytoma(PC12) cells. METHODS: We treated antipsychotics(chlorpromazine, haloperidol, and risperidone) and antidepressants(amitriptyline, fluoxetine, and moclobemide) at 0.1-10 microM concentrations before application of Abeta(10 microM), and compared with control in the absence of psychotropic drugs in cultured PC12 cells. RESULTS: 1) Chlorpromazine, haloperidol and risperidone significantly reduced Abeta-induced cytotoxicity in PC12 cells. 2) Amitriptyline, fluoxetine, and moclobemide significantly reduced Abeta-induced cytotoxicity in PC12 cells. CONCLUSION: Our results suggest that psychotropic drugs in the treatment of dementia of Alzheimer's type may protect the neural cells as well as control neurotransmitter activities.
Amitriptyline ; Amyloid ; Amyloid beta-Peptides ; Animals ; Chlorpromazine ; Dementia ; Depression ; Fluoxetine ; Haloperidol ; Moclobemide ; Neurons ; Neurotransmitter Agents ; PC12 Cells* ; Psychotropic Drugs* ; Rats ; Risperidone

A 53 year-old male patient with major depressive disorder visited due to various depressive symptoms. According to his past medical history, he had no definite medical problems including hypertension, diabetes mellitus or arteriosclerosis, which affect on sexual function. When his first visit to our outpatient clinic, we administered imipramine and moclobemide and subsequently tried various antidepressants including fluoxetine, paroxetine, and venlafaxine. During the treatment the patient was continuously suffered from erectile dysfunction but he had not notified his erectile dysfunction. Incidentally, after his discontinuation of prescribed antidepressant, he was recovered from his erectile dysfunction and so, he thought his erectile dysfunction was due to antidepressants. After 3 year treatment of antidepressant, the patient and doctor realized his erectile dysfunction was caused by antidepressants. Although the prescribed antidepressant was change to venlafaxine which was known to have less sexual side effects, the patient's erectile dysfunction was continued. But venlafaxine was substituted with mianserin which is 5-HT 2 receptor antagonist, the patient's erectile dysfunction was improved dramatically in 20 days after mianserin administration. It is necessary to assess various side effects of antidepressant regularly and intensively. We recommend that antidepressant should be changed instantly when serious sexual side effects occur or should be considered with administration of 5-HT 2 antagonist which is known to have less sexual dysfunction like as mianserin or some other new antidepressants considered to have little sexual dysfunction.
Ambulatory Care Facilities ; Antidepressive Agents ; Arteriosclerosis ; Depression ; Depressive Disorder, Major ; Diabetes Mellitus ; Erectile Dysfunction* ; Fluoxetine ; Humans ; Hypertension ; Imipramine ; Male ; Mianserin* ; Middle Aged ; Moclobemide ; Paroxetine ; Serotonin ; Venlafaxine Hydrochloride

PURPOSES: The authors derived two forecasting models which can be used as objective tools for detecting epidemics and predicting the future frequencies of communicable diseases. METHODS: In this study, regression analysis using trigonometric functions, Box and Jenkins's seasonal ARIMA model were applied to the monthly accumulated data of five nationally notifiable communicable diseases from January 1987 to December 1998 in Korea. RESULTS: Between two forecasting models, seasonal ARIMA model gives more precise predicted frequencies than regression model in the neighborhood of the current time points and future time, but the regression model is better in overall agreement between the predicted and observed frequencies during 7 years(1992-1998). CONCLUSIONS: These forecasting models can be usefully applied in deciding and carrying out a national policy in preventing epidemics in the future, and graphic program is much helpful to understand the present status of disease occurrence.
Communicable Diseases* ; Forecasting* ; Korea* ; Moclobemide ; Residence Characteristics ; Seasons