• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.392-398
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• 2021

In this study, we determined the effect of 24 different synthetic 4-benzylpiperidine carboxamides on the reuptake of serotonin, norepinephrine, and dopamine (DA), and characterized their structure-activity relationship. The compounds with a two-carbon linker inhibited DA reuptake with much higher potency than those with a three-carbon linker. Among the aromatic ring substituents, biphenyl and diphenyl groups played a critical role in determining the selectivity of the 4-benzylpiperidine carboxamides toward the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. Compounds with a 2-naphthyl ring were found to exhibit a higher degree of inhibition on the norepinephrine transporter (NET) and SERT than those with a 1-naphthyl ring. A docking simulation using a triple reuptake inhibitor 8k and a serotonin/norepinephrine reuptake inhibitor 7j showed that the regions spanning transmembrane domain (TM)1, TM3, and TM6 form the ligand binding pocket. The compound 8k bound tightly to the binding pocket of all three monoamine reuptake transporters; however, 7j showed poor docking with DAT. Co-expression of DAT with the dopamine D₂ receptor (D₂R) significantly inhibited DA-induced endocytosis of D₂R probably by reuptaking DA into the cells. Pretreatment of the cells with 8f, which is one of the compounds with good inhibitory activity on DAT, blocked DAT-induced inhibition of D₂R endocytosis. In summary, this study identified critical structural features contributing to the selectivity of a molecule for each of the monoamine transporters, critical residues on the compounds that bound to the transporters, and the functional role of a DA reuptake inhibitor in regulating D₂R function.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.229-234
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• 2010

섬유근통 증후군은 만성 전신 통증을 나타내며 피곤, 두통, 우울증, 수면장애 등을 동반하는 질환이다. 주로 30-50대의 여성에게서 많이 나타나며 미국에서 2-4%, 한국에서 2%의 발병률을 보이고 있다. 정확한 원인과 기전이 밝혀져 있지 않아서 진단과 치료에 많은 논란과 어려움이 있다. 현재는 증상치료에 목표를 두고 삼환계항우울약을 많이 사용하고 있으나 심각한 부작용의 문제가 있다. 이러한 문제 때문에 최근에는 selective serotonin reuptake inhibitor (SSRI) 또는 serotonin-norepinephrine reuptake inhibitor (SNRI)를 빈번히 사용하고 있다. 본 연구는 SNRI의 하나인 milnacipran의 섬유근통 증후군 치료에 대한 효능 및 안정성을 알아보기 위해, MEDLINE에 등재된 논문을 기한없이 milnacipran과 fibromyalgia로 검색하여 무작위 배정 및 이중맹검 임상연구자료들을 선별하였다. 선별된 6개의 임상연구 결과, milnacipran를 사용했을 때 일관된 효능성과 안정성이 관찰되었고 섬유근통증후군 치료와 그에 수반되는 여러증상에 효과적인 것으로 나타났다.

• Journal of Yeungnam Medical Science
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• v.36 no.3
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• pp.249-253
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• 2019

There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.509-517
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• 2019

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through $5-HT_3$ receptors. Using a wholecell voltage clamp method, we recorded currents of $5-HT_3$ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. $EC_{50}$ of 5-HT on $5-HT_3$ receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of $5-HT_3$ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated $5-HT_3$ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit $5-HT_3$ receptor currents in a non-competitive manner with the mechanism of open channel blocking.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.168-178
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• 1997

The serotonin has been known to play important roles in pathology of the mood disorders. We summerize the evidences of serotonin in pathology of the mood disroders in a view of neuroanatomical and neurochemical aspects. Nowaday, the selective serotonin reuptake inhibitors(SSRIs) may be practically the first line of antidepressants with traditional tricyclic antidepressants(TCAs). Authors review the role of serotonin in the treatment of the mood disorders, in a view of the general considerations in selecting antidepressants, pharmacology, therapeutic indications, side effects, doses of medication, drug-discontinuation syndrome, drug-to-drug interactions, and special therapeutic situations.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.415-421
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• 2017

We investigated the inhibitory effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent $K^+$ (Kv) channels in freshly separated from rabbit coronary arterial smooth muscle cells. The application of escitalopram rapidly inhibited vascular Kv channels. Kv currents were progressively inhibited by an increase in the concentrations of escitalopram, suggesting that escitalopram inhibited vascular Kv currents in a concentration-dependent manner. The $IC_{50}$ value and Hill coefficient for escitalopram-induced inhibition of Kv channels were $9.54{\pm}1.33{\mu}M$ and $0.75{\pm}0.10$, respectively. Addition of escitalopram did not alter the steady-state activation and inactivation curves, suggesting that the voltage sensors of the channels were not affected. Pretreatment with inhibitors of Kv1.5 and/or Kv2.1 did not affect the inhibitory action of escitalopram on vascular Kv channels. From these results, we concluded that escitalopram decreased the vascular Kv current in a concentration-dependent manner, independent of serotonin reuptake inhibition.

• Korean Journal of Psychosomatic Medicine
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• v.29 no.2
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• pp.153-161
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• 2021

Objectives : The purpose of this study is to compare bleeding tendency of selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) using platelet function analyzer (PFA-100) in patients with major depressive disorder. Methods : This study is a prospective open-label study conducted by a single institution. A total of 41 subjects diagnosed with major depressive disorder under the DSM-5 diagnostic criteria participated in this study. The subjects were classified into SSRI (escitalopram) groups and SNRI (duloxetine) groups, respectively, according to random assignments. The closure time (CT) was measured using a platelet function analyzer (PFA-100) before each antidepressant was administered and after 6 weeks. Paired-sample t-test was conducted within each group to determine whether a specific antidepressant had an effect on closure time. In order to confirm the relative change in platelet function between the two groups, an independent sample t-test was conducted to compare and analyze the change in closure time between the two groups. Results : There was no significant changes in closure time (CEPI-CT, CADP-CT) before and 6 weeks after drug administration in the SSRI and SNRI groups, and there was no difference in the amount of changes in closure time between the two groups. Conclusions : Our results showed no difference in bleeding tendency between SSRI and SNRI. This study suggests that further large-scale studies on bleeding tendency for various antidepressants are needed in the future.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.1
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• pp.72-80
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• 2020

Objectives : The aim of this study was to compare the effect of Selective Serotonin Reuptake Inhibitor (SSRI) and Serotonin Norepinephrine Reuptake Inhibitor (SNRI) for mood symptoms, pain, and somatic symptoms in elderly depression patients with pain and somatic symptoms. Methods : This study is a prospective open-label study conducted by a single institution. A total of 43 subjects diagnosed with major depressive disorder under the DSM-5 diagnostic criteria participated in this study (average age: 72.53, 58.1% women). The subjects were classified as SSRI and SNRI groups. Depressive symptoms, pain, and somatic symptoms were evaluated by Korean version of the Hamilton Depression Rating Scale (K-HDRS), visual analogue scale (VAS) and Patient Health Questionnare-15 (PHQ-15) respectively at baseline and six weeks later. Two-way repeated-measure ANOVA was performed to analyze changes in the KHDRS, VAS, and PHQ-15 scores. Results : In the SSRI and SNRI groups, K-HDRS, VAS, and PHQ-15 all showed significant improvement after 6 weeks compared to each baseline values. There were no differences in therapeutic effect between the two groups. Conclusions : We found that SSRI and SNRI both improved somatic symptoms and pain in elderly depression patients. The results of this study are thought to help select antidepressants when administering medication to elderly depression patients who complain pain and somatic symptoms. Further research is needed on the longterm effects of the SSRI and SNRI.

• Korean Journal of Psychosomatic Medicine
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• v.21 no.2
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• pp.81-92
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• 2013

Newer antidepressants are commonly used in clinical practice to treat psychiatric disorder and psychosomatic disorder including chronic pain syndrome, fibromyalgia, headache. However there are many unexpected adverse effects of these drugs such as nausea and vomiting, weight gain, sexual dysfunction. These are 3 most well-recognized common adverse effects of newer antidepressant and are most common causes of treatment failure. I reviewed mechanisms, epidemiology, and pharmacological management of these adverse effects of newer antidepressants. In this paper, newer antidepressants include selective serotonin reuptake inhibitor(fluoxetine, fluvoxamine, citalopram, escitalopram, sertraline, paroxetine), serotonin norepinephrine reuptake inhibitor(venlafaxine, duloxetine), norepinephrine and dopamine reuptake inhibitor(bupropion), noradrenergic and specific serotonergic antidepressant(mirtazapine), and reversible inhibitor of MAO-A(moclobemide). I suggest that psychiatrists and clinicians in the psychosomatic field should know mechanisms, epidemiology, and management of these common and well-recognized adverse effects of newer antidepressants. Therefore it will be helpful to recognize easily and treat well for patients with psychiatric disorder and psychosomatic disorder using newer antidepressants.

• CELLMED
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• v.9 no.2
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• pp.2.1-2.1
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• 2019

Depression is common psychiatric diseases characterized by diverse physical and emotional symptoms including low mood, loss of interest in pleasurable activities, and feelings of worthlessness. Depression causes of death and disability. The first antidepressant was created by the idea that central serotonin mechanism. Selective serotonin reuptake inhibitor, fluoxetine is the first-line drug in the treatment of depressive disorder and their few side effects as opposed to tricyclic antidepressants. Not all people with depression respond adequately to standard treatments. Korean music playing/listening actions appear to be a reliable approach to developing recovery from depression.