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Beneficial effects of antidepressant mirtazapine in functional dyspepsia patients with weight loss

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World Journal of Gastroenterology 2016年第22期22卷 5260-5266页

作者： Shu-Man Jiang Lin Jia Jing Liu Man-Man Shi Ming-Zhi Xu Department of Gastroenterology Guangzhou First People’s Hospital Guangzhou Medical University Department of Gastroenterology Guangzhou Nansha Central Hospital Department of Psychology Guangdong General Hospital

AIM: To explore the effects and mechanism of action of antidepressant mirtazapine in functional dyspepsia(FD) patients with weight ***: Sixty depressive FD patients with weight loss were randomly divided into a mirtazapine group(MG), a paroxetine group(PG) or a conventional therapy group(CG) for an 8-wk clinical trial. Adverse effects and treatment response were recorded. The Nepean Dyspepsia Index-symptom(NDSI) checklist and the 17-item Hamilton Rating Scale of Depression(HAMD-17) were used to evaluate dyspepsia and depressive symptoms, respectively. The body composition analyzer was used to measure body weight and fat. Serum hormone levels were measured by ***:(1) After 2 wk of treatment, NDSI scores were significantly lower for the MG than for the PG and CG;(2) After 4 or 8 wk of treatment, HAMD-17 scores were significantly lower for the MG and PG than for the CG;(3) After 8 wk of treatment, patients in the MG experienced a weight gain of 3.58 ± 1.57 kg, which was significantly higher than that observed for patients in the PG and CG. Body fat increased by 2.77 ± 0.14kg, the body fat ratio rose by 4%, and the visceral fat area increased by 7.56 ± 2.25 cm2; and(4) For the MG, serum hormone levels of ghrelin, neuropeptide Y(NPY), motilin(MTL) and gastrin(GAS) were significantly upregulated; in contrast, those of leptin, 5-hydroxytryptamine(5-HT) and cholecystokinin(CCK) were significantly downregulated. CONCLUSION: mirtazapine not only alleviates symptoms associated with dyspepsia and depression linked to FD in patients with weight loss but also significantly increases body weight(mainly the visceral fat in body fat). The likely mechanism of mirtazapine action is regulation of brain-gut or gastrointestinal hormone levels.

关键词： mirtazapine Functional dyspepsia weight loss Depression

Determination of the antidepressant effect of mirtazapine augmented with caffeine using Swiss-albino mice

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 239-240页

作者： Alexis Danielle Y.Co Carlos Miguel Calderon ANDrea Tracy G.Cunanan Kristin Almira B.De Guzman Rosvielentine V.Rosales Melchin Edreen O.Tapan Deric S.Vengua Gavino Ivan Tanodra Faculty of Pharmacy University of Santo Tomas

Depression is a serious health condition affecting an estimate of 350 million people *** with antidepressants as first line treatment however is found to have limited benefits as compared to augmentation *** agents such as caffeine,when added to the antidepressants are found to have positive effects with depression by acting as an antagonist to adenosine *** Swiss albino mice were grouped into six,first three groups with arbitrary doses of the combination of mirtazapine and caffeine and last three control groups being the untreated,mirtazapine-treated and caffeine-treated groups.

关键词： mirtazapine Caffeine Tail Suspension Test Forced Swim Test Immobility time Depression

Development and Validation of an LC-MS/MS Method for Quantitative Analysis of mirtazapine in Human Plasma

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American Journal of Analytical Chemistry 2011年第6期2卷 650-657页

作者： Marlus Chorilli Rudy Bonfilio Caroline Rossim Louvandini Francine Andressa Rosa Madia Goncalves Herida Regina Nunes Salgado Departamento de Farmacos e Medicamentos Faculdade de Ciencias FarmaceuticasUniversidade Estadual Paulista Julio de Mesquita FilhoRodovia Araraquara-JauAraraquara-SPBrazil Universidade Metodista de Piracicaba Rodovia do AcucarPiracicaba-SPBrazil

mirtazapine (MTZ) is an antidepressant drug, which belongs to the chemical class of piperazinoazepines. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantifica- tion of MTZ in plasma at the concentrations associated with therapy. Diazepam (DZP) was used as internal standard, added to 200 μL of plasma sample prior to a liquid-liquid extraction using hexane. Chroma- tographic separation was achieved on an Agilent? Eclipse XDB C-18 column (100 × 2.1 mm, 3.5 μm) in iso- cratic mode at 40?C. Mobile phase was 10 mM ammonium acetate/acetonitrile/formic acid (60/40/0.1, v/v/v) at a constant flow rate of 0.5 mL?min–1. The injection volume was 10 ?L and the total run time was 3.2 min. The method shows selectivity and linearity. The detection and quantitation limits were established at 0.17 and 0.50 ng?mL–1, respectively. The extraction recoveries for MTZ and DZP were found to be between 84.9 and 93.9%. The intra-day and inter-day precision and accuracy fulfill at the international acceptance criteria. The method shows to be stable for the studied parameters. Therefore, a rapid, specific, and sensitive LC-MS/MS method for quantification of MTZ in human plasma was developed and can be used in therapeu- tic drug monitoring of this drug.

关键词： mirtazapine High-Performance Liquid Chromatography Mass Spectrometry Human Plasma

Aqueous Solubility Enhancement of mirtazapine: Effect of Cosolvent and Surfactant

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Pharmacology & Pharmacy 2015年第10期6卷 471-476页

作者： Kenneth E. Ezealisiji Chika J. Mbah Patience O. Osadebe Department of Pharmaceutical Chemistry Faculty of Pharmaceutical Sciences University of Port Harcourt Port Harcourt Nigeria Department of Pharmaceutical and Medicinal Chemistry Faculty of Pharmaceutical Sciences University of Nigeria Nsukka Nigeria

The poor aqueous solubility of drugs is a challenging problem faced by pharmaceutical scientists in drug formulation. Cosolvency and micellization techniques have been severally used to enhance the solubility of poorly aqueous soluble drugs. mirtazapine, a tetracyclic antidepressant used for the treatment of moderate to severe depression and anxiety, has very poor aqueous solubility. The objective of the study was to investigate the effect of solubilizing agents (cosolvents and surfactants) on the aqueous solubility of mirtazapine while envisaging that any significant improvement in its aqueous solubility could contribute towards alleviating the withdrawal symptoms often associated with the drug. The solubility of mirtazapine was determined at room temperature in aqueous mixtures of cosolvents (propylene glycol and polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80 and sodium lauryl sulfate). An exponential increase in mirtazapine solubility was observed when total drug solubility in water-cosolvent system was plotted against cosolvent fraction volume. Polyethylene glycol 400 gave larger solubilization capacity (σ) when compared to propylene glycol. With the surfactants, linear relationship between the total solubility of the drug in water-surfactant mixtures and surfactant concentration was noted. Sodium lauryl sulfate showed the largest solubilization power (k) when compared to the nonionic surfactants (polysorbate 20 and polysorbate 80 respectively). A linear relationship between standard free energy and partition coefficient was also observed. The result of the study shows that aqueous solubility of mirtazapine is significantly improved by cosolvency and micellization and therefore there exists the possibility of improving the withdrawal symptoms often experienced with the drug. It also suggests that large free energy is required for drugs with high partition coefficients to permeate the biological membrane.

关键词： mirtazapine Cosolvency Micellization Aqueous Solubility

Development and validation of HPLC methods for enantioseparation of mirtazapine enantiomers at analytical and semipreparative scale using polysaccharide chiral stationary phases

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Development and validation of HPLC methods for enantiosepara...

抗抑郁药—mirtazapine（米它扎平）

30th International Symposium on Capillary Chromatography、4th GC×GC Symposium、16th National Symposium and Exhibition on Chromatography,i.e. 1st Dalian International Symposium and Exhibition on Chromatography

作者： Zong-de Zhai~(1 2) Yan-Ping Shi~(1 *) 1.Key Laboratory for Natural Medicine of Gansu Province Lanzhou Institute of Chemical Physics Chinese Academy of Sciences Lanzhou 730000 China 2.Graduate University of Chinese Academy of Sciences Beijing 100039 China

＜正＞mirtazapine is a recent noradrenergic and specific serotonergic antidepressant（NaSSA）drug,and used to treat moderately and severely depressed hospitalized and *** HPLC methods were developed for the analytical and semipreparative resolution of new antidepressant drug mirtazapine *** analytical scale,the separation of the mirtazapine enantiomers was investigated using both cellulose and amylose tris（3,5- dimethylphenylcarbamate）（CDMPC and ADMPC）chiral stationary phases under normal-phases and polar organic *** good baseline enantioseparation was achieved in all ***,the elution order of mirtazapine enantiomic pairs was found reversed by changing the stationary phase from the amylose-based ADMPC-CSPs to its cellulose-based counterpart,*** validation of the analytical methods including linearity,limit of detection,limit of guantitation,recovery and precision,together with the semipreparative resolution of mirtazapine racemate were carried out using cellulose tris （3,5-dimethyiphenylcarbamate）chiral stationary phases and methanol as mobile phase without any basic additives under polar organic *** analytical scale,the elution times of both enantiomers were less than 6 min at room temperature and 1.0 ml/min,with the separation factor（α）1.99 and the resolution facotor（Rs）3.56. Then,the analytical methods were scaled up to semipreparative loading to obtain small amount of both mirtazapine *** semipreparative scale,about 16 mg/h enantiomers could be isolated and elution times of both enantiomers were less than 10 min at 2.0 ml/*** increase the throughput,the technique of boxcar injections was *** enantiomer（（-）-（R）-mirtazapine）was isolated with purity of ＞99.9% *** ＞98.0% yield and another（（+）-（S）-mirtazapine）was isolated with purity of ＞97.0% *** ＞99.0% *** addition,optical rotation and circular dichroism spectroscopy of both mirtazapine enantiomers isolated were also investi

关键词： Enantioseparation polysaccharide carbamate phase semipreparative HPLC optical rotation circular dichroism mirtazapine

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国外新药介绍 2001年第1期 16-18页

作者：朱晓红

Determination of mirtazapine in Human Plasma by HPLC-MS and Bioavailability of Newly Developed mirtazapine Tablets in Healthy Volunteers

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Journal of Chinese Pharmaceutical Sciences 2004年第3期13卷 171-175页

作者： LIRong-shan DINGLi JIANLong-hai XIAOHong DepartmentofPharmaceuticalAnalysis ChinaPharmaceuticalUniversityNanjing210009China NationalDrugClinicalResearchBase NanjingBrainHospitalNanjing210029China

Aim To establish a sensitive and specific liquid chromatography-mass spectrometry method for determination of mirtazapine in human plasma and evaluation of its relative bioavailability. Methods After being alkalized by 25% ammonia, mirtazapine in the plasma was extracted with n-hexane. Desloratadine was used as internal standard (IS). Solu-tes were separated on a C_(18) column with a mobile phase of methanol-ammonium acetate buffer (pH 3.5) (75∶25). The flow rate of the mobile phase was 1 mL·min^(-1). Detection was performed on an electrospray ionization (ESI) mass spectrometer and operated in selected ion monitoring (SIM) and positive-ionization mode using target ionsat m/z 266.2 for mirtazapine and m/z 311.2 for the IS. The fragmentor voltage was 90 V. A randomized cross-over study was performed in 20 healthy volunteers. In the two study periods, twenty healthy Chinese male subjects received a single oral dose of mirtazapine 30 mg. Results The calibration curve was linear over the range of 0.3-200 ng·mL^(-1). The limit of quantitation was 0.1 ng·mL^(-1). The parameters for mirtazapine test tablet and reference tablet were as follows: T_(1/2)(24.7±4.1) and (23.6±4.3) h, T_(max)(1.6±0.8) and (1.5±0.8) h, C_(max)(95.9±29.8) and (91.9±26.7) ng·mL^(-1), respectively. Conclusion The established HPLC-MS method is rapid, sensitive and specific for the determination of mirtazapine in human plasma. The relative bioavailability was 100.0%±10.8%.

关键词： mirtazapine pharmacokinetics bioavailability HPLC-MS

mirtazapine对呼吸暂停治疗有潜力

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国外药讯 2003年第9期 17-17页

作者：李燕燕

Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

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World Journal of Gastroenterology 2008年第27期14卷 4377-4382页

作者： Lin Jia Yuan-Yuan Shang Yu-Yuan Li Department of Digestive Diseases Guangzhou Municipal First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was n

关键词： Pancreatic carcinoma mirtazapine Fluoxetine Body weight Nude mice Locomotor activity Ethology