• The Korean Journal of Pain
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• 제28권3호
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• pp.185-192
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• 2015

Background: Neuropathic pain is a global clinical problem; nevertheless, nerve injury treatment methods remain limited. Olanzapine has antinociceptive and anti-nueropathic properties; however, its preventive effects have not been assessed in nerve injury models. Methods: We prepared a partial sciatic nerve ligation (Seltzer model) or sham-operated model in male Sprague-Dawley rats under isoflurane anesthesia. In a pre-treatment study, we administered olanzapine (10 mg/kg) intraperitoneally 1 h before nerve ligation. In post-treatment and dose-dependent studies, we injected 3 different doses of olanzapine intraperitoneally 1 h after nerve ligation. Mechanical allodynia was measured before and 7 days after surgery. Immunohistochemical analysis using anti-Iba-1 antibody was used to assess the effect of olanzapine at the spinal level. Results: In the pre-treatment study, median withdrawal thresholds of the normal saline groups were significantly lower than those of the sham-operated groups; however, those of the olanzapine (10 mg/kg) and sham-operated groups were not different. In the post-treatment and dose-dependent studies, the median withdrawal thresholds of the olanzapine (2.5 mg/kg) and normal saline groups were not different; however, those of the olanzapine (10 and 50 mg/kg) groups were significantly higher than those of the normal saline groups. Olanzapine did not have a significant effect on the density of Iba-1 staining. Conclusions: Olanzapine attenuated mechanical allodynia dose-dependently in the Seltzer model. This anti-allodynic effect of olanzapine was observed even when injected 1 h after nerve ligation. This effect of olanzapine appeared to be unrelated to microglia activation in the ipsilateral dorsal horn of the lumbar spinal cord.

• 생물정신의학
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• 제7권1호
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• pp.74-79
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• 2000

본 연구의 목적은 치료 용량의 비정형적 항정신병 약물(risperidone, olanzapine)의 성 호르몬(prolactin과 testosterone)에 대한 효과를 알아보기 위해 총 91명의 정신분열병 환자들의 혈청에서 prolactin과 testosterone의 농도를 측정하였다(haloperidol 28명, 4~20mg/day ; risperidone 31명, 2~6mg/day ; olanzapine 32명, 5~20mg/day). 그 결과 남자 환자에서 olanzapine 복용자의 혈청 prolactin 농도가 risperidone이나 haloperidol 복용자의 혈청 농도보다 낮았으나 risperidone 복용자와 haloperidol 복용자의 혈청 prolactin 농도는 상호 유의한 차이가 없었다. 여자 환자에서는 olanzapine 복용자의 혈청 prolactin 농도가 risperidone이나 haloperidol 복용자의 혈청 농도보다 낮았으며 risperidone 복용자의 prolactin 농도는 haloperidol 복용자보다 낮았다. 또한 남자, 여자 환자 모두에서 haloperidol, risperidone, olanzapine을 각각 복용한 사람들의 혈청 testosterone 농도는 유의한 차이가 없었다. 위의 결과로 저자는 치료 용량에서 risperidone은 혈청 prolactin 농도를 haloperidol 만큼이나 증가시키지만 olanzapine의 경우 혈청 prolactin 농도에는 영향을 끼치지 않으며 비정형적 항정신병 약물은 testosteron의 농도에는 영향을 끼치지 않는다는 것을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8107-8113
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• 2014

The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy in glioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay, was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cells was significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst 33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy with increased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growth inhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagy inhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 glioma cells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level of Bcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cells was shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mouse xenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by induction of autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells.

• BMB Reports
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• 제55권6호
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• pp.293-298
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• 2022

Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

• 생물정신의학
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• 제8권1호
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• pp.140-146
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• 2001

In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

• Bulletin of the Korean Chemical Society
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• 제34권9호
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• pp.2567-2568
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• 2013

• 생명과학회지
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• 제29권9호
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• pp.1010-1015
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• 2019

카할세포는 위장관에서 향도잡이 역할을 한다. 본연구에서는 생쥐 소장 카할세포에서 발생되는 향도잡이 기능에서 올란자핀의 역할을 연구하였다. 패치클램프 방법을 사용하여 향도잡이 전압을 측정하였다. 올란자핀에 의해서 카할세포 향도잡이 전압이 탈분극 되었으며, 이 탈분극은 무스카린성 3번 수용체 억제제에 의해서 억제 되었다. 세포내 $GDP{\beta}S$을 넣어주니 올란자핀에 의해 향도잡이 전압 탈분극이 억제되었다. 또한, 세포밖 $Na^+$ 농도 감소와 비선택성 양이온 통로 억제제에 의해서 올란자핀에 의한 향도잡이 전압 탈분극이 억제 되었다. 세포내 PLC기전의 억제제인 U-73122에 의해서 올란자핀에 의한 향도잡이 전압 탈분극이 억제 되었다. 이러한 결과로 올란자핀은 무스카린성 3번 수용체를 통해서 세포내 G 단백질과 PLC기전 및 세포밖 $Na^+$이 관여함을 알 수 있었다. 따라서 올란자핀은 카할세포를 통해서 장운동성을 조절 할 수 있을 것으로 생각된다.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.282-291
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• 2007

Although the etiology of schizophrenia is known to be linked with the disturbance of glutamatergic and dopaminergic neurotransmission, little is known about the relationship between gene expression and the disease process. To identify genes related to abnormalities in glutamatergic and dopaminergic function, we investigated the effects of olanzapine in the changes of mRNA levels in the animal model of schizophrenia, using a high-density DNA microarray. Olanzapine (3.0 mg/kg, i.p.) significantly reduced hyperlocomotive activities, which was induced by MK-801 (1.0 mg/kg, i.p.). We identified that the expression of 719 genes were significantly altered more than two folds in the prefrontal cortex of the rats treated with MK-801. We selected 15 genes out of them by the changes of the expression pattern in the treatment of Olanzapine and/or MK801 for the further confirmation in RT-PCR. The administration of MK-801 increased the expression of 7 genes (NOS3, Hspb1, Hspa1a, CRH, Serpine1, Igfbp6, Snf1lk) and decreased the expression of 1 gene (Aldh1a2), which was attenuated by olanzapine. One gene (Prss12) was up-regulated after olanzapine treatment although it did not show the significant changes after MK-801 treatment. These results showed that antipsychotic drug, such as olanzapine, may alter the gene expression patterns, which were accompanied by MK-801-induced psychosis. Our results also provide us high-density DNA microarray technology could be potential approaches to find the candidate molecules for the therapeutics and also for the early diagnosis of psychiatric diseases.

• 생물정신의학
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• 제24권3호
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• pp.162-166
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• 2017

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, medication-induced hypersensitivity reaction with long latency. It is characterized by fever, rash, leukocytosis with eosinophilia, atypical lymphocytosis, and internal organ involvement. The most common causes of DRESS syndrome are sulfonamides and anticonvulsants such as carbamazepine and lamotrigine. However, valproic acid and olanzapine could develop DRESS syndrome. We report a case of DRESS syndrome associated with valproic acid and olanzapine in a 41 years old male patient with bipolar disorder.

• 약학회지
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• 제52권4호
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• pp.288-292
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• 2008

Olanzapine, an atypical antipsychotic, has been widely used for the treatment of schizophrenia and bipolar disease. Although olanzapine is less associated with extrapyramidal symptoms and neuroleptic malignant syndrome compared to existing typical antipsychotics, the use of this drug has a problematic side effect of weight gain, which may cause metabolic syndrome such as type 2 diabetes. However, there are few hospitals practicing body weight monitoring of the patients on olanzapine or other atypical antipsychotics. The goal of this study was to identify the incidence and severity of weight gain associated with the use of the drug in Korea. We performed body weight monitoring of the patients who were on the drug in a hospital setting. Mean of the weight gain (as of one-month-transformation) was 4.33 and 3.39 kg for the male and female patients, respectively. The incidence in the young patients was higher than that observed in the old patients, and the severity was the highest in patients in their thirties followed by twenties or younger. This result suggests that the pattern of the weight gain associated with the use of olanzapine in Korea is similar to the reports performed and documented in US and European countries. Therefore, it appears that healthcare professionals in Korea should also watch on the weight gain issue in patients who are on olanzapine or other atypical antipsychotics.