• Korean Journal of Acupuncture
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• 제24권1호
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• pp.13-25
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• 2007

목 적 : 흡연에 따른 건강적 피해가 많이 알려져 있음에도 불구하고 특히 여성 및 청소년 계층의 흡연이 증가하고 있으며 폐암 사망자수는 급격히 늘어나고 있는 상황이다. 완전한 금연이 실패하는 주요 이유는 담배의 중독성에서 비롯되며 금단현상을 극복하지 못해 일어나는 것으로 알려져 있다. 흡연의 중독성은 담배 주요성분 중의 하나인 니코틴(nicotine)에 의해 유발되며 따라서 모든 금연 요법 및 금연 치료보조제 들은 이 니코틴 작용을 어떻게 효과적으로 억제 또는 대체하느냐에 초점을 맞추고 있다. 최근 금연치료 요법으로 한방 침이 주목 받고 있으며 본 논문을 통해 한방 침의 금연효과에 대한 신경학적 기전을 고찰하고자 한다. 방 법 : 금연을 돕는 전형적인 보조 치료제 및 치료법이 몇 종류 개발되어 사용 중에 있으며 대표적으로 니코틴 대체 요법(nicotine replacement therapy, NRT)이나 항우울제로 사용되는 bupropion 등을 들 수 있다. 이 치료 방법들은 뇌의 도파민계 신경전달 체계에 영향을 미쳐 금연 효과를 발휘하게 되는데 실질적인 금연성공확률은 그리 높지 않은 것으로 알려져 있다 따라서 침의 자극에 대한 도파민계 신경전달 조절효과를 중심으로 고찰함으로써 침의 금연효과에 대한 의과학적 기전을 설명하고자 하였다. 결 과 : 침자극은 우수한 금연효과를 가져올 수 있는 치료법으로 기존의 금연 치료요법 및 치료제 들을 보완할 수 있는 보다 확실한 치료요법 중의 하나이며 특히 금연 후에 오는 금단현상을 효과적으로 완화시키는 작용을 한다. 그리고 이 같은 효과는 부분적으로 도파민계를 비롯한 신경전달계를 조절함으로써 가능한 것으로 판단된다. 결 론 : 본 논문을 통해 니코틴에 의한 금단현상의 신경학적 기전과 금연과 관련된 신경전달체계에 대한 침자극의 효능에 대해 고찰하였으며 기존의 금연보조치료법을 대체할 수 있는 우수한 의학적 치료법으로써의 침치료법을 제시하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.379-385
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• 2016

TWIK-related $K^+$ channel-2 (TREK-2) and TWIK-related spinal cord $K^+$ (TRESK) channel are members of two-pore domain $K^+$ channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specific activators of TREK-2 and TRESK may be beneficial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently.

• 약학회지
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• 제57권4호
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• pp.289-292
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• 2013

A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.84-88
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• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Journal of Korean Medical Science
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• 제33권46호
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• pp.290.1-290.11
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• 2018

Background: The role of antidepressants (ADs) in bipolar disorder is long-standing controversial issue in psychiatry. Many clinicians have used ADs as a treatment for bipolar depression, and the selection of therapeutic agents is very diverse and inconsistent. This study aimed to examine recent AD prescription patterns for patients with bipolar disorder in Korea, using the nationwide, population-based data. Methods: This study utilized the Korean nationwide, whole population-based registry data of the year 2010, 2011, and 2013. All prescription data of the ADs, antipsychotics, and mood stabilizers of the sampled patients diagnosed with bipolar disorder (n = 2,022 [in 2010]; 2,038 [in 2011]; 2,626 [in 2013]) were analyzed for each year. Results: Annual prescription rate of ADs was 27.3%-33.6% in bipolar disorder, which was gradually increasing over the 3-year period. The combination pattern of ADs and antipsychotic drugs tended to increase over 3 years. The proportion of females and the prevalence of comorbid anxiety disorder were significantly higher in AD user group in all three years. Among individual ADs, escitalopram was prescribed most frequently, and fluoxetine and bupropion were prescribed to the next many patients. The mean duration of bipolar depressive episodes was 135.90-152.53 days, of which ADs were prescribed for 115.60-121.98 days. Conclusion: Our results show prescription rate of ADs in bipolar disorder was maintained at substantial level and increased in recent 3 years. More empirical data and evidence are needed to establish practical treatment consensuses.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제13권1호
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• pp.129-138
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• 2002

목 적：소아청소년 정신과 질환의 가장 대표적이라 할 수 있는 주의력결핍-과잉행동장애(ADHD)의 최적치료모델 개발을 위한 연구의 일환으로, 우선 실제 ADHD로 의심되는 환자가 병원을 방문했을 때 임상의들이 현재 (1) 어떠한 진단 평가적 도구를 사용하여 진단적 접근을 하며, (2) 어떠한 치료적 접근을 시행하고 있는지, (3) 현재 시행하고 있지는 않지만, 어떤 모델을 추구하는지에 대해 구조화된 설문도구를 이용하여 파악하고자 하였다. 방 법：대학병원 및 종합병원 소아정신과 담당 전문가 32명을 대상으로 구조화된 설문조사를 하였고, 여기에 포함되는 조사내용으로는 진단검사도구, 약물치료, 비약물치료 현황파악이었다. 이 자료를 Texas Algorithm Project(TAP)와 비교 검토하였다. 결 과：(1) 모든 ADHD 환아에게 실시해야 할 기본적인 검사는 지능검사, 문장완성검사, 지속적 집중력검사, 코너씨 설문지였고, (2) 전반적 ADHD 투여 약물은 TAP 지침과 차이가 없었고, 다만 약효가 인정된 aderall, bupropion, guanfacin의 국내이용이 요구된다고 하였으며, (3) 틱 장애가 동반된 경우는 임상의들이 정신자극제 사용을 자제하는 경향을 보여 TAP 지침과 분명한 차이를 보였고, (4) 파탄적 행동장애가 동반된경우 임상의들은 다른 약물로 교체하기보다는 MPH 투여에 다른 약물을 추가하는 경향을 보였으며, (5) 과반수 이상의 임상의가 꼭 실시하여야 한다고 보고한 치료로는, 개별적 부모상담, 부모교실, 개인별 행동인지 치료였다. 결 론：본 연구 결과를 통해 알 수 있었던 여러 제한점들을 보완하고 또한 본 연구에서 제기된 논쟁점을 위주로 하여서, 한국적 실정에 맞는 ADHD 최적치료모델 개발을 위한 연구와 더불어 전문가들의 합의가 이루어져야 하겠다.

• Journal of Microbiology and Biotechnology
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• 제22권12호
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• pp.1659-1664
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• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

• 생명과학회지
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• 제17권3호통권83호
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• pp.334-339
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• 2007

본 연구는 우황청심원을 비롯한 상용되는 20종의 한약제제를 대상으로 9종의 시토크롬 동종효소에 대한 대사능의 저해정도를 고속 스크리닝 기법을 이용하여 탐색함으로써, 한약제제와 약물의 병용으로 인한 약물 상호작용 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 9종의 주요 시토크롬 약물대사효소의 지표약물과NADPH-generating system및 한약제제(500 ${\mu}g/ml$)를 첨가한 후 $37^{\circ}C$에서 15분간 반응시켜 생성된 각각의 대사물을 LC/MS/MS를 이용하여 정량하여 시토크롬 동종효소 활성의 변화를 평가하였다. 그 결과 우황청심원 현탁액 및 황련해독탕 물 추출물이 각각 CYP2B6 및 CYP2D6 효소 활성을 선택적으로 강력하게 저해하였다. 이러한 결과는 약국에서 쉽게 구입할 수 있는 한약제제들 중 일부는 인체 간 시토크롬 활성 저해능을 가지고 있고, 이들 효소에 의해 대사되는 약물과의 병용 복용시 약물상호작용 발생 가능성이 있음을 의미한다. 향후 한약제제에서 저해능을 나타내는 주된 성분을 규명하여 이 성분의 저해능과 저해 기전을 살피는 노력이 필요할 것이다.

• 대한조현병학회지
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• 제22권2호
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• pp.21-33
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• 2019

Objectives: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. Methods: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. Results: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. Conclusion: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.