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

OBJECTIVE: We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. METHODS: With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine, asenapine, iloperidone, lurasidone, perospirone and blonanserin. We applied some bibliometric indicators of paper production and dispersion with Price's law and Bradford's law, respectively. We also calculated the participation index (PI) of the different countries, and correlated the bibliometric data with some social and health data from Korea (such as total per capita expenditure on health and gross domestic expenditure on research and development). RESULTS: We collected 326 original papers published between 1993 and 2011. Our results state fulfilment of fulfilled Price's law, with scientific production on SGAs showing exponential growth (correlation coefficient r=0.8978, as against an r=0.8149 after linear adjustment). The most widely studied drugs were risperidone (91 papers), aripiprazole (77), olanzapine (53), and clozapine (43). Division into Bradford zones yielded a nucleus occupied by the Progress in Neuro-Psychopharmacology and Biological Psychiatry (36 articles). A total of 86 different journals were published, with 4 of the first 10 used journals having an impact factor being greater than 4. CONCLUSION: The publications on SGAs in South Korea have undergone exponential growth over the studied period, without evidence of reaching a saturation point.
Antipsychotic Agents ; Benzodiazepines ; Biological Psychiatry ; Bipolar Disorder ; Clozapine ; Complement Factor B ; Dibenzothiazepines ; Dibenzothiepins ; Health Expenditures ; Heterocyclic Compounds with 4 or More Rings ; Imidazoles ; Indoles ; Isoindoles ; Isoxazoles ; Jurisprudence ; Korea ; Piperazines ; Piperidines ; Pyrimidines ; Quinolones ; Republic of Korea ; Risperidone ; Schizophrenia ; Subject Headings ; Sulpiride ; Thiazoles ; Quetiapine Fumarate ; Aripiprazole ; Lurasidone Hydrochloride

A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC50 values at micromolar range. Compounds I1 (IC50 value of 0.086 μmol · L(-1)) and I2 (IC50 value of 0.080 μmol · L(-1)) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC50 value of 0.094 μmol · L(-1)). Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.
Animals ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Dioxoles ; chemical synthesis ; chemistry ; Drug Design ; Indans ; Inhibitory Concentration 50 ; Isoindoles ; chemical synthesis ; chemistry ; Memory Disorders ; drug therapy ; Mice ; Piperidines ; Scopolamine Hydrobromide

OBJECTIVESTo establish a HPLC method for determination of N-methylcantharidimide in dogs' plasma and to study the pharmacokinetics of N-methylcantharidimide in dogs'.

METHODThe plasma samples were extracted by methanol. The acetonitrile and the purified water composed mobile phase. The flow rate was 0. 7 mL x min(-1), ultraviolet detection wavelength was at 212 nm.

RESULTThe calibration curve was linear over the range from 0.01-10.0 mg x L(-1) with a correlation coefficiency of 0.996 3. The lower limit of quantitation was 0.01 mg x L(-1). The mean recovery was 92.3%. the relative standard deviation (RSD) of intra-day and inter-day were all less than 10%. After intravenous administration of N-methylcantharidimide with 3 dosages of 10, 15, 20 mg x kg(-1) to dogs, the corresponding distribution half-livers (t1/2alpha) were 1.8, 2.1, 1.7 min, and the elimination half-lives (t1/2beta) were 144,139, 146 min, respectively.

CONCLUSIONThis method is convenient, accurate and reliable. It can be used for determination of N-methylcantharidimide in dogs' plasma and pharmacokinetic studies.

Animals ; Area Under Curve ; Cantharidin ; administration & dosage ; analogs & derivatives ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Female ; Isoindoles ; administration & dosage ; blood ; Male

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

Ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate is a potential intermediate for the synthesis of HMG-CoA reductase inhibitor (atorvastatin) that can lower the cholesterol level in human blood. In this study, in order to synthesize ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate by bioreduction, the yeast strains in our lab were screened. Ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate was found to be produced efficiently from ethyl 5-(1,3-dioxoisoindolin-2-yl)-3-oxopentanoate by Pichia pastoris X-33. The effects of initial substrate concentration, reaction time, co-substrate, amount of yeast cells, pH, as well as the temperature on the yield and enantiomeric excesses (e.e. value) of product were examined in mono-phase system. The optimal reaction conditions are as fallows: substrate concentration 7 g/L, cell concentration 120 g/L, glucose concentration 120 g/L, pH 6.5, temperature 35 degrees C, reaction time 12 h, and the yield 93.12% with the high e.e. value of 98.55%.
Anticholesteremic Agents ; metabolism ; Atorvastatin Calcium ; Catalysis ; Enzymes ; metabolism ; Fermentation ; Heptanoic Acids ; metabolism ; Isoindoles ; metabolism ; Oxidation-Reduction ; Pentanoic Acids ; metabolism ; Pichia ; genetics ; metabolism ; Pyrroles ; metabolism ; Stereoisomerism

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.
Aspirin/therapeutic use* ; Clopidogrel/therapeutic use* ; Coronary Artery Bypass/adverse effects* ; Drug Therapy, Combination ; Humans ; Isoindoles ; Male ; Phenylbutyrates ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Treatment Outcome

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.
Genotype ; Hand ; Humans ; Isoindoles ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Risperidone ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins ; Tandem Repeat Sequences ; Thiazoles

AIMTo design and synthesize new compounds of prandial glucose regulator with more simple structure.

METHODSThe target compounds were synthesized from diethyl succinate and benzaldehyde or 4-fluorobenzaldehyde by four-step reactions. Thus 18 compounds were synthesized. Their structures were comfirmed by NMR, MS and IR.

RESULTSSeventeen compounds had different hypoglycemic activity in mice, among them, 9 compounds had higher hypoglycemic activity and 6 compounds had character of prandial glucose regulator.

CONCLUSIONPart of the compounds have higher hypoglycemic activity deserve to be further investigated.

Animals ; Benzylidene Compounds ; chemical synthesis ; chemistry ; pharmacology ; Blood Glucose ; metabolism ; Carbamates ; chemical synthesis ; chemistry ; Cyclohexanes ; chemical synthesis ; chemistry ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; Isoindoles ; Mice ; Molecular Structure ; Phenylalanine ; analogs & derivatives ; chemical synthesis ; chemistry ; Piperidines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Succinates ; chemical synthesis ; chemistry ; pharmacology

Until now, we do not have specific Korean data on the age related prostatic volume and voiding symptoms associated with prostatic volume among randomized aged population. Due to this problem, we studied the correlations on the age, prostatic volume and voiding symptom among random sampled 255 people over the age 60 from the 11 Myun in Chinyang Gun, Kyungsangnam-do from the July 12th to July 26th, 1993. The mean age of the examined people was 71.5 years. 244 people answered on questionaire for voiding symptom scoring and 224 people agreed on the transrectal ultrasonic measurement of the prostatic volume. The prolate spheroid method and elliptical method were used for the measurement of the prostatic volume with the major transverse diameter, major anteroposterior diameter and cephalocaudal diameter of each prostates as Terris. The volume of the prostate ranged from 6.2cc to 54.5cc ( Prolate spheroid method ) and 4.7cc to 44.1cc(Elliptical method ). The prostate volumes measured by the elliptical method were smaller than that measured by prolate spheroid method in each age group. The average prostatic volume measured by the elliptical volume and prolate spheroid method were 17.7/22.5cc(E/P) in age 61 to 65 group(n=17), 19.9/22.8cc in age 66 to 70 group(n= 88), 21.6/ 26.0cc in age 71 to 75 group(n=71), 24.4/27.7cc in age 76 to 80 group(n=34) and 18.1/23.7cc in age over 80 group(n =14) and the pattern of the changes in the prostatic volume related with aging was significant(p <0.05 ). The voiding symptom scores were measured and divided according to the prostate volume into 3 groups, below 20cc, 20.1 to 30 and over 30cc groups. The voiding symptom scores ranged from 0 to 35 and the mean symptom scores were 10.9, 11.7 and 14.1 in each group and these changes were not statistically significant(p>0.05).
Aging ; Humans ; Phosmet ; Prostate ; Ultrasonics