• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• 동의생리병리학회지
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• 제20권4호
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• pp.830-843
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• 2006

Clinical evidence suggests that Nelumbinis Semen extracts have antidepressive properties and may offer an interesting alternative for the treatment of mood disorders. It was the aim of the present study to compare the effects of Nelumbinis Semen extracts with those of fluoxetine and hypericum perforatum extract in the rat forced swimming test (FST) and chronic mild stress (CMS), a model of depression. In the FST, p.o. administration of Nelumbinis Semen extracts (1 mg) induced a statistically significant reduction of immobility. The active behaviors in that test did not reflect decreased general activity because Nelumbinis Semen extracts failed to alter the locomotor activity of rats, measured in the open field test. Moreover Nelumbinis Semen extracts was superior to fluoxetine and hypericum perforatum extract in the incidence of sexual side-effects. These effects of Nelumbinis Semen extracts on the rat behavior is to be ascribed to increased Cytochrome c oxidase polypeptide Vla-liver, Mitogen-activated protein kinase 1 , Adenylosuccinate synthetase, and Aldehyde dehydrogenase in rat hippocampus.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.189-195
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• 2021

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 μM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 μM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.

• 대한한방내과학회지
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• 제35권2호
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• pp.145-156
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• 2014

Objectives : The aim of this study was to compare Tianwangbuxin-dan to Fluoxetine for antidepressive efficacy and safety in poststroke depression (PSD). Methods : A randomized, double blinded, non-inferiority trial was conducted. 113 PSD patients were recruited from a stroke center. Except for the 25 excluded patients, 88 PSD patients were randomly given either Tianwangbuxin-dan 1100 mg or Fluoxetine 20 mg per a day for 16 weeks. PSD was evaluated using Beck's depression inventory (BDI) and Hamilton depression rating scale (HDRS) and followed every fourth week. Repeated measure analysis of variance (ANOVA) was used to compare and contrast the depression scores of the two groups and to compare them among the evaluation times, at the beginning, $4^{th}$, $8^{th}$, $12^{th}$ and $16^{th}$ weeks. In addition, independent t-tests were used to find the difference between two groups at every evaluation time. Results : Finally, 88 PSD patients were included in the study, 63 PSD patients completed the procedure and 25 PSD patients were dropped out by the incompliance or withdrawal of consent. Tianwangbuxin-dan (or Fluoxetine) improved the depression of stroke patients and the efficacy of Tianwangbuxin-dan was not inferior to that of Fluoxetine. In addition, there was no significant side effect in two groups. Conclusions : This study showed that antidepressive efficacy and safety of Tianwangbuxin-dan in PSD patients.

• Journal of Pharmaceutical Investigation
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• 제29권2호
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• pp.151-156
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• 1999

Bioequivalence of two fluoxetine capsules, the $Prozac^{\circledR}$ (Daewoong Lilly Pharmaceutical Co., Ltd.) and the $Lucetin^{\circledR}$ (Kyungdong Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Twenty normal male volunteers $(21{\sim}30\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three capsules containing 20 mg of fluoxetine per capsule were orally administered, blood was taken at predetermined time intervals, and the concentrations of fluoxetine in serum were determined using HPLC method with UV detector. The pharmacokinetic parameters ($AUC_t$, $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for the statistical analysis of parameters. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two capsules based on $Lucetin^{\circledR}$ capsules were -8.01 %, -7.02% and 1.49%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 84.72%, 96.68% and 83.06%, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$. All the parameters above met the criteria of KFDA for bioequivalence, indicating that $Lucetin^{\circledR}$ capsule is bioequivalent to $Prozac^{\circledR}$ capsule.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제8권1호
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• pp.133-138
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• 1997

Prader-Willi 증후군(Prader-Willi Syndrome, PWS)은 $50{\sim}-70%$ 정도의 환자에서 염색체 15번에 이상이 있음이 보고된 유전적인 질환으로서, 그 특징적인 임상양상은 심한 근긴장의 저하(hypotonia), 반사소실(areflexia), 섭식의 곤란(feeding difficulty), 저체온증(hypothermia), 성기왜소증(microgenitalia), 음낭저형성증(hypoplastic scrotum), 대식증(polyphagia), 포만감의 감소와 비만, 정신운동발달의 지연, 저성선기능증(hypogonadism) 및 안면과 척추의 기형 등이다. 또한 행동상의 여러 문제들이 동반되는데 분노발작, 피부를 심하게 뜯거나 발모광, 과도한 식욕과 관련된 음식 도벽증이 나타나므로 정신과적 치료가 필요하다. 본 증례는 14세된 PWS환자로서 비만과 대식증, 도벽증, 학업부진 및 생활부적응 문제 등으로 2주간의 입원과 약 1년간의 추적기간 동안 약물요법(fluoxetine 투여)과 행동요법, 그리고 가족요법을 받아 왔다. 장기간의 Fluoxetine투여를 통하여 비만과 식욕의 조절에는 효과가 만족스럽지 않았으나 우울감과 감정문제, 자살사고 및 행동문제들은 호전되었다.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.69-85
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• 2023

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.

• 생물정신의학
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• 제16권1호
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• pp.5-14
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• 2009

Objectives : Most of the mechanisms reported for antidepressant drugs are the enhancement of neurite outgrowth and neuronal survival in the rat hippocampus. Neural cell adhesion molecule 140(NCAM140) has been implicated as having a role in cell-cell adhesion, neurite outgrowth, and synaptic plasticity. In this report, we have performed to elucidate a correlation among chronic antidepressant treatments, NCAM140 expression, and activation of phosphorylated cyclicAMP responsive element binding protein(pCREB) which is a downstream molecule of NCAM140-mediated intracellular signaling pathway in the rat hippocampus. Methods : Fluoxetine(10mg/kg) was injected acutely(daily injection for 5days) or chronically(daily injection for 14days) in adult rats. RNA and protein were extracted from the rat hippocampus, respectively. Real-time RT-PCR was performed to analyze the expression pattern of NCAM140 gene and western blot analyses for the activation of the phosphorylation ratio of CREB. Results : Chronic fluoxetine treatments increased NCAM140 expression 1.3 times higher than control in rat hippocampus. pCREB immunoreactivity in the rat hippocampus with chronic fluoxetine treatment was increased 4.0 times higher than that of control. Conclusion : Chronic fluoxetine treatment increased NCAM140 expression and pCREB activity in the rat hippocampus. Our data suggest that NCAM140 and pCREB may play a role in the clinical efficacy of antidepressants promoting the neurite outgrowth and neuronal survival.

• 한국산학기술학회논문지
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• 제13권5호
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• pp.2125-2132
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• 2012

Fluoxetine과 tianeptine은 보편적으로 사용되는 항우울제 (AD)이며, haloperidol과 risperidone도 많이 사용되는 항정신성 (APD) 약물로 다양한 이온채널을 조절한다. TREK2 채널은 우울증과 정신분열증 같은 정신질환에 대한 병태생리학적으로 중요한 역할을 하는 TREK1 채널과 생리학적 성질이 매우 비슷하여, 정신성 및 우울증 약물의 TREK2 채널에 대한 효과가 TREK1과 유사하게 나타날 가능성이 있다. Excised inside-out 팻취 방법을 사용하여, 클론된 TREK2 채널이 발현된 CHO 세포에서 항정신성 약물과 항우울제의 효과를 조사했다. Fluoxetine (선택적 세로토닌 방출 억제제, SSRI)은 TREK2 채널을 농도 의존적으로 억제하였으나 ($IC_{50}=13{\mu}M$), tianeptine (선택적 세로토닌 재흡수 증가제, SSRE)은 TREK2 채널 활성을 감소시키지 않고 증가시켰다. Haloperidol은 TREK2 채널을 농도 의존적으로 억제하였으나 ($IC_{50}=44{\mu}M$), risperidone은 고농도 ($100{\mu}M$)에서도 TREK2 채널 활성을 완전히 억제 시키지 못했다. 본 연구는 tianeptine 보다 fluoxetine이 TREK2 채널을 더 잘 억제하고 risperidone 보다 haloperidol에 더 잘 억제됨을 보여 주었고, TREK2 채널에 대한 항정신성 약물과 항우울제의 차별적 작용이 약물 부작용의 어떤 기전에 기여 할 수 있음을 제시한다.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1996년도 정기총회 및 추계학술대회
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• pp.37-37
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• 1996