• Archives of Pharmacal Research
• /
• 제27권1호
• /
• pp.94-98
• /
• 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.

• 생물정신의학
• /
• 제1권1호
• /
• pp.40-59
• /
• 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.

• 생물정신의학
• /
• 제26권1호
• /
• pp.14-21
• /
• 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.

• 대한약리학회지
• /
• 제30권3호
• /
• pp.343-349
• /
• 1994

정신병치료제들을 장기투여하여 치료를 시도하였을 때에 생기는 여러 부작용은 그 정도 또한 매우 심각하기 때문에 그들의 치료효과와 함께 야기되는 부작용들을 따로 생각할 수가 없게 되었다. 특히 정신병치료는 그 자체에 대한 병인적 원인을 정확히 알 수 없기에 증상에 따른 대중요법이 일괄적으로 사용되므로, 이러한 현재의 치료방법으로는 부작용들이 더 치명적이 될 수 있기 때문에 일차적으로 이들의 공통적약리작용기전들을 연구하는 것은 매우 필요하다. 최근 NO(Nitric oxide)에 대한 많은 연구들에 의하면, 이들이 중추신경계에서 중요한 second messenger 또는 mediator로 신경활동에 영향을 나타내는 것으로 보고되고 있다. 그러므로 저자들은 먼저 이들 약물들과 NO와의 관계를 연구하고자, 중요한 몇종의 정신병치료제들을 택하여 NO생성에 어떤 영향을 미치는 가를 검색하여 다음과 같은 일차 결과를 얻었다 1. 정신병치료제 수종(chlorpromazine, trifluoperazine promazine, pimozide, clozapine, chlorprothixene, haloperidol)을 택하여 쥐의 소내에서 $[^3H]L-arginine$으로부터 $[^3H]L-citrulline$의 생성양을 측정하여 calmodulin antagonist(calmidazolium)와 비교하였다. 2. 이들을 N1E-115 cell에 투여하여 $[^3H]cyclic$ GMP양을 측정하고 그 결과를 calmida-zolium 과 비교하였다. 3. 이들 약물들은 citrulline과 cyclic GMP 모두의 생성양을 의의있게 억제하였으며 그 기전은 calmidazolium과 매우 유사하였다. 위의 일차적 검색결과에 의하면, 정신병치료약물들의 약리작용 기전중에 일부는 중추신경계내의 NO생성 및 cyclic GMP생성에 영향을 나타내는 것으로 사료되며, 이에는 calcium ion이 상당히 중요한 역할을 하는데, 특히 소뇌에서의 NO생성의 감소는 이들 약물들의 치명적 부작용인 tardive dyskinesia와 매우 깊은 관련을 추측할 수 있다. 그러나, 더 많은 약물들의 검색으로 일관적인 기본 결과가 필요 되고 또 각개 약물의 특정적 기전이 연구되기 위하여 현재 실험중이다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• 제14권2호
• /
• pp.157-173
• /
• 2003

성인기에 비하여 소아의 정신약물학은 역사도 짧고 아직 체계도 잡혀 있지 않은 상태이다. 약물의 안정성, 효능, 장기 투여에 따르는 부작용에 대한 연구도 아직 초보적인 수준이다. 임상적인 측면에 있어서도 항우울제, 항정신병약물, 중추신경흥분제 등에 대한 반응이 성인기와는 일부 다른 반응을 보이기도 한다. 또한 연구분야에 있어서도 연구 윤리상 성인기에 비하여 많은 제한이 있다. 이에 본고에서는 발달학적 약역학에서는 약물의 흡수, 분포, 대사 및 배설과정에 있어서 어떠한 차이가 있는가를 살펴보았다. 아울러 특정 약물(항정신병약물, 항우울제, lithium, 중추신경흥분제, 항경련제 등)의 약역학에 대하여도 그 특성을 논하였다. 발달학적 약동학에서는 주요 수용체의 개체발생적인 과정과 그 과정이 갖는 임상적인 의미에 대하여 논하였다. 약물유전학적 측면에서는 약물유전학의 약역학적 측면, 약동학적 측면에 대하여 논하였다. Dopamine 관련 대립인자와 관련된 연관연구들에 있어서는 주의력결핍, 과잉운동장애, 뚜렛증후군에 대한 연구들에 대하여 살펴보았다. 대립인자와 관련된 약물유전연구에 있어서는 dopamine 수용체의 다형성과 clozapine, bromocriptine, haloperidol, methylphenidate에 대한 반응과의 관련성에 대하여 살펴보았다. 또한 serotonin 관련 수용체의 다형성과 약물반응과의 연관성에 대하여도 함께 논하였다. 이러한 연구들을 바탕으로 향후 소아 또는 청소년기의 약물투여에 있어서 발달학적인 특성과 함께 개인적인 특성이 고려된 투약이 시행되어야 할 것이다.

• 한국약용작물학회지
• /
• 제24권5호
• /
• pp.341-350
• /
• 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.