• Archives of Pharmacal Research
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• v.27 no.1
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• pp.94-98
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• 2004

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells ($IC_{50}$ values, 10-20$\mu$M). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.40-59
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• 1994

The introduction of lithium salts for the treatment of mood disorder by Code in 1949 was a major therapeutic breakthrough. Yet it is far from the universal therpeutic agent in the treatment of mood disorders. Indeed, some acutely manic patients do not respond adeqately to lithium and some individuals experience breakthrough affective episodes during lithium maintenance. In the last decode, it has become c1ear that a significant number of patients with more highly recurrent disorders may require alternative or enhanced forms of prophylactic treatment. For these reasons, a variety of other drugs hove been employed for the treatment and prophylaxis of mood disorders. Efforts to develop new pharmacologic strategies for mood disorder hove included a diverse array of medications, ranging from potent benzodiazepines to novel neuroleptics and from anticonvulsants to calcium channel blockers. The anticonvulsants appear particularly useful in cases of dysphoric mania and rapid cycling state, subforms of bipolar disorder that respond quite poorly to conventional treatments. Among all of these new pharmacologic strategy, carbamazepine and sodium valproate have received the broadest clinical applications as maintenance therapies. The data documenting the short-term antimanic effectiveness of the calcium channel blocker verapamil and benzodiazepins such as clonazepam and lorazepam appear also promising. A number of other theoretically interesting, as well as clinically relevant therapies, which are not presently employed routinly, hove also been studied, including 2 blocker clonidine, atypical antipsychotic clozapine, cholinomimetics, 5-HT enhancers, thyroid and magnesium preparations. Now prophylaxis in mood disorder remains a considerable therapeutic challenge. Controlled testing of the prophylactic efficacy of compounds such as carbamazepine, valproic acid, and the calcium channel blockers represent important next step in the clinical trials for mood disorder.

• Korean Journal of Biological Psychiatry
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• v.26 no.1
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• pp.14-21
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• 2019

Objectives Thyroid hormone deficiency during the neurodevelopmental period can impair brain development and induce psychiatric symptoms. This study examined the association between thyroid dysfunction and the severity of symptoms in schizophrenia patients, and the treatment response of patients with schizophrenia. Methods Three hundred thirty-eight schizophrenia patients, with no prior history of thyroid disease or taking medication associated with it, were studied. We assessed the blood thyroid hormone level, the Brief Psychiatric Rating Scale (BPRS) scores on the day of admission and discharge, admission period, dose of administered antipsychotics, and the number of antipsychotic combinations. The collected data were subsequently analyzed using the Kruskal-Wallis test and Pearson's chi-square test. Results The percentage of schizophrenia patients who presented with abnormal thyroid hormone level was 24.6%. High total triiodothyronine (TT3) (p = 0.003), low TT3 (p = 0.001), and high free thyroxine (fT4) (p < 0.001) groups showed a higher BPRS score on admission than did the normal thyroid hormone group, while thyroid stimulating hormone (TSH) levels were not significantly correlated with the severity of symptoms. Furthermore, thyroid hormone was not associated with the treatment response assessed by the rate of BPRS score reduction, admission days, use of clozapine, and dose of antipsychotics. Conclusions The TT3 and fT4 hormone levels were significantly associated with the severity of symptoms in schizophrenia patients. These relations suggested that thyroid dysfunction may be associated with the severity of schizophrenia. And hence, further analysis of the results of the thyroid function test, which is commonly used in cases of psychiatric admission, is required.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.343-349
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• 1994

A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.14 no.2
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• pp.157-173
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• 2003

The history of pediatric psychopharmacology is very short and the research on safety, efficacy and side effects is preliminary and long-term effect on growth and maturation is not well known yet. Clinical findings have shown that the responses to antidepressants, antipsychotics, CNS stimulants and steroids in children and adolescents might be different from adult populations. Based on these findings, this paper reviewed three issues, Firstly, in developmental pharmacokinetics. the author discussed the developmental factors affecting drug absorption, distribution, protein-binding, metabolism and excretion. Secondly, in developmental pharmacodynamics, developmental characteristics of dopamine, serotonin, norepinephrine receptors and their clinical implications were reviewed. Lastly, in pharamcogenetic part, the clinical utility of pharmacogenetics, pharmacokinetic aspects of pharmacogenetics, the pharmacodynamic aspects of pharmacogenetics, the association studies of dopamine-related alleles in neuropsychiatric disorders such as attention-deficit hyperactivity disorders or Tourette’s disorders, pharmacogenetic studies dopamine-related alleles and the pharmacogenetic studies of serotonin-related alleles. Based on these preliminary research, future pharmacogenetic applications in childhood and adolescent psychiatry were also discussed.

• Korean Journal of Medicinal Crop Science
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• v.24 no.5
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• pp.341-350
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• 2016

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5 mg/kg, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100 mg/kg) and injections of clozapine (5 mg/kg) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIA-induced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.