• YAKHAK HOEJI
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• v.55 no.2
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• pp.91-97
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• 2011

To search a new anti-depressant agents against para-chloroamphetamine-induced excitation, three dimensional quantitative-structure relationships (3D-QSAR) models between structure of 3a,4-dihydro-3H-[1]-benzopyronao[4,3]isoxazoles (1-30) and thieir inhibitory activity against para-chloroamphetamine-induced excitation were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. From these basis on the findings, the optimized CoMSIA-2F model ($q^2$=0.793 and $r^2$=0.952) showed the best statistical results. And also, it is found that the para-chloroamphetamine inhibitory activity from the optimized CoMSIA-2F model was dependent on steric field (35.2%) and electrostatic field (64.8%) of tricyclic isoxazoles. Particularly, it is predicted that the inhibitory activity against para-chloroamphetamine-induced excitation will be able to increase by the designed compounds from the CoMSIA-2F model.

• The Korean Journal of Pain
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• v.31 no.1
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• pp.3-9
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• 2018

Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation. Other substances, not used in the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics are also associated with long QT syndrome. When the possible benefits of therapy outweigh the associated risks, slow dose titration and electrocardiography monitoring are recommended.

• The Korean Journal of Pain
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• v.23 no.2
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• pp.99-108
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• 2010

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel ${\alpha}2-{\delta}$ ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.274-280
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• 1999

A variety of mechanism may generate pain resulting from injury to the central and peripheral nervous system. None of these mechanism is disease-specific, and several different pain mechanism may be simultaneously present in anyone patient, independent of diagnosis. Diagnosis of neuropathic pain is often easily made from information gathered on neurologic examination and from patient history. Although treatment of neuropathic pain may be difficult, optimum treatment can be achieved if the neurologist has a complete understanding of therapeutic options, the mainstay of which is pharmacotherapy. Selection of an appropriate rharmacologic agent is by trial and error since individual responses to different agents, doses, and serum levels are highly variable. An adequate trial for each agent tried is key to pharmacologic treatment of neuropathic pain. Tricyclic antidepressants are first-line agents, although other drugs, including anticonvulsants, local anesthetic antiarrhythmics, clonidine, opiates, and certain topical agents, also offer pain relief in some patient populations. The novel antidepressants venlafaxine and nefazodone are potentially useful new drugs that are better tolerated than tricyclic antidepressants. Also Gabapentine seems an interesting and promising drug for the treatment of neuropathic pain.

• Journal of Integrative Natural Science
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• v.9 no.2
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• pp.128-135
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• 2016

5-hydroxytryptamine (serotonin) receptor ($5-HT_7R$) 7 is one of G-Protein coupled receptors, which is activated by the neurotransmitter Serotonin. After activation by serotonin, $5-HT_7$ activates the production of the intracellular signaling molecule cyclic AMP. $5-HT_7$ receptor has been found to be involved in the pathophysiology of various disorders. It is reported that $5-HT_7$ receptor antagonists can be used as antidepressant agents. In this study, we report the important structural and chemical parameters for 2-methoxyphenylpiperazinylakanamides as $5-HT_7R$ inhibitors. A 3D QSAR study based on comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with $q^2$ of 0.594 with 6 components, $r^2$ of 0.986, Fisher value as 60.607, and an estimated standard error of 0.043. The predictive ability of the test set was 0.602. Results obtained the CoMFA models suggest that the data are well fitted and have high predictive ability. The contour maps are generated and studied. The contour analyses may serve as tool in the future for designing of novel and more potent $5-HT_7R$ derivatives.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.259-263
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• 1999

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes $5-HT_{2A}$ and ${\alpha}_1$ adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT2 antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.161-169
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• 1999

There are a number of approaches in developing experimental models for depression, but there is no such thing as a best model for depressive syndrome. Animal models are subject to the obvious limitations inherent in the assumption that human psychopathology can be represented accurately in lower animals. Recently, the concern increasingly is to develop a variety of experimental paradigms in animals to study selected aspects of human psychopathology, and animal models should be understood as basically experimental preparations that are developed to carry out these objects. Therefore, a battery of a variety of animal models should be applied to permit detailed pathophysiological studies and to develop new antidepressant treatments. Animal models of depression basically consider behavioral isomorphism with the human depression a plus, but not a req-uirement, and the model behavior should be defined operationally in order to be reproduced reliably by other researchers and be responsive to those agents possessing demonstrated clinical efficacy in human depression. In conclusion, animal models of depression have played a significant role in elucidating pathophysiology of depression and developing current treatments for depression, but there is no single comprehensive model for depression until now. Each of the proposed animal model has its advantages and limitations. In other words, certain paradigms are suitable for studying certain phenomena, whereas others are more suitable for studying other aspects. The best model for depression depends upon what the question is.

• The Korean Journal of Pain
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• v.27 no.2
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• pp.118-124
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• 2014

Background: The chronic pain can disturb physical, psychological, and social performances. Analgesic agents are widely used but some antidepressants (ADs) showed analgesia also. Bupropion is using for smoke cessation but it can change morphine withdrawal signs such as pain. This study tested the acute systemic effect of bupropion on formalin induced pain behavior in rats. Methods: Wistar male healthy rats were divided into 7 groups (control, sham, and 5 treated groups with 10, 30, 90, 120, and 200 mg/kg of bupropion, i.p.). The bupropion injected 3 hours prior to formalin induced pain behavior. Formalin (50 ${\mu}l$, 2.5%) was injected subcutaneously in dorsal region of right hindpaw in all animals. Nociceptive signs were observed continuously on-line and off-line each minute. Common pain scoring was used for pain assessment. Results: The analysis of data by one-way ANOVA showed that bupropion can reduce pain scores in the second phase but not in first phase. Bupropion decreased the licking/biting duration significantly in first and second phase of formalin test. Conclusions: The results showed that bupropion has analgesic effects at systemic application. The change of second phase of the pain behavior was significant and it revealed that central mechanisms involve in bupropion analgesia.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.40-47
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• 2020

Background: Duloxetine is an antidepressant that is also useful in chronic neuropathic and central origin pain. In this study, the role of duloxetine in decreasing acute postoperative pain after lumbar canal stenosis surgery is explored. Methods: In this single center, triple blinded, and placebo-controlled trial, 96 patients were randomized for statistical analysis. The intervention group received oral duloxetine 30 mg once a day (OD) for 2 days before surgery, 60 mg OD from the day of surgery to the postoperative second day and 30 mg OD for the next 2 days (a total duration of 7 days). A placebo capsule was given in the other group for a similar time and schedule. The same standard perioperative analgesia protocols were followed in both groups. Results: Total morphine consumption up to 24 hours was significantly decreased in the duloxetine group (P < 0.01). The time to the first analgesia requirement was similar in both groups but the time to the second and third dose of rescue analgesia increased significantly in the duloxetine group. The time to ambulation was decreased significantly (P < 0.01) in the duloxetine group as compared to the placebo group. Pain scores remained similar during most of the time interval. No significant difference was observed in the complication rate and patient satisfaction score recorded. Conclusions: Duloxetine reduces postoperative pain after lumbar canal stenosis surgery with no increase in adverse effects.

• Journal of Korean Medical Science
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• v.33 no.46
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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.