Moclobemide (Ro 111163)
(Synonyms: 吗氯贝胺; Ro111163) 目录号 : GC11703
Moclobemide (Ro 111163)是一种可透过血脑屏障的可逆的单胺氧化酶A（MAO-A）抑制剂，对hMAO-A的IC50值为6.061μM。
Cas No.:71320-77-9
Sample solution is provided at 25 µL, 10mM.
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Moclobemide (Ro 111163) is a reversible monoamine oxidase A (MAO-A) inhibitor that can cross the blood-brain barrier, with an IC50 value of 6.061μM for hMAO-A[1]. Moclobemide is a classic antidepressant that increases the levels of brain monoamines (such as serotonin, norepinephrine, and dopamine)[2, 3]. Moclobemide can be used to treat mental illnesses such as social anxiety disorder[4].
In vitro, treatment of hypoxic or glutamate-stimulated neuron-astrocyte co-cultures with Moclobemide (10-100µM) significantly increased the number of surviving neurons[5]. Treatment of mixed glial cell cultures with Moclobemide (10-8-100µM) significantly inhibited the LPS-induced increase in TNF-α, IL-1β, and IL-10 mRNA levels in mixed glial cell cultures[6].
In vivo, treatment of chronically stressed mice with Moclobemide (40mg/kg) via intraperitoneal injection significantly increased the number of BrdU-positive cells in the subgranular zone of the hippocampus, upregulated hippocampal progenitor cell proliferation, and reversed the stress-induced decrease in brain-derived neurotrophic factor (BDNF) levels in the hippocampus of mice[7].
References:
[1] Can NÖ, Osmaniye D, Levent S, Sağlık BN, İnci B, Ilgın S, Özkay Y, Kaplancıklı ZA. Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity. Molecules. 2017 Aug 20;22(8):1381.
[2] Fitton, Andrew, Diana Faulds, and Karen L. Goa. Moclobemide: a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 43.4 (1992): 561-596.
[3] Haefely, W., et al. Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology 106.Suppl 1 (1992): S6-S14.
[4] Nutt, D., and S. A. Montgomery. Moclobemide in the treatment of social phobia. International clinical psychopharmacology 11 (1996): 77-82.
[5] Verleye M, Steinschneider R, Bernard F X, et al. Moclobemide attenuates anoxia and glutamate-induced neuronal damage in vitro independently of interaction with glutamate receptor subtypes[J]. Brain research, 2007, 1138: 30-38.
[6] Bielecka A M, Paul-Samojedny M, Obuchowicz E. Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated primary mixed glial cell culture[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2010, 382(5): 409-417.
[7] Li YF, Zhang YZ, Liu YQ, Wang HL, Yuan L, Luo ZP. Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice. Acta Pharmacol Sin. 2004 Nov;25(11):1408-12. PMID: 15525460.
Moclobemide (Ro 111163)是一种可透过血脑屏障的可逆的单胺氧化酶A（MAO-A）抑制剂，对hMAO-A的IC50值为6.061μM[1]。Moclobemide是经典的抗抑郁药，能提高脑单胺（如5-羟色胺受体、去甲肾上腺素、多巴胺）的水平[2, 3]。Moclobemide能够用于社交焦虑障碍等精神疾病的治疗[4]。
在体外，Moclobemide（10-100µM）处理缺氧或谷氨酸刺激的神经-星体胶质培养物，显著增加了存活神经元的数量[5]。Moclobemide（10-8-100µM）处理混合神经胶质细胞培养物，显著抑制了LPS诱导的混合神经胶质细胞培养物中TNF-α、IL-1β和IL-10 mRNA的水平升高[6]。
在体内，Moclobemide（40mg/kg）通过腹腔注射治疗慢性应激小鼠，显著增加了小鼠海马体颗粒下区的BrdU阳性细胞数量，上调了海马祖细胞的增殖，逆转了应激造成的小鼠海马体内脑源性神经营养因子（BDNF）水平的降低[7]。
| Cell experiment [1]: | |
Cell lines | Neuronal-astroglial cultures from rat cerebral cortex |
Preparation Method | At the time of the neuronal injury procedure, the medium was replaced by the growth medium containing Moclobemide at different concentrations (10, 30 and 100μM) or basic fibroblast growth factor (bFGF) at 10ng/ml chosen as a positive reference to assess the assay suitability. Moclobemide and bFGF were prepared in DMSO as 100mM or 50μg/ml stock solutions, respectively. Control cultures received the DMSO vehicle alone and the final concentration of DMSO never exceeded 0.1% (v/v). Two types of protocols were then used from the same cell culture: (i) At the 10th day in culture, for anoxia, Moclobemide (or bFGF) solution was added to medium consisting of Dulbecco's modified Eagle culture medium/Ham's nutrient mixture (DMEM–HamF12). Anoxia was induced by placing the cultured cells treated with Moclobemide (or bFGF) or vehicle in a humidified and O2-deprivedchamber at 37°C for 5 and 7h (100% N2). At the end of the anoxia period, the medium pH was 7.4 and cultures returned to normoxic conditions at 37°C without any renewal of the medium for 19 and 17h before fixing and neuronal immunolabelling. Concurrently, control cell cultures in the same growth medium, which were not exposed to anoxic conditions, were maintained in a humidified 5% CO2/95% air atmosphere at 37°C for 24h and then fixed in the same conditions as previously. (ii) After 12 days in culture, neuronal injury was induced by exposing cell cultures treated with Moclobemide (or bFGF) or vehicle to L-glutamate at a 2mM concentration for 6h in Eagle minimal essential medium (MEM) containing 2mM L-glutamine and 1% N2 supplement. Control cultures were exposed to the culture medium without L-glutamate over the same time before fixing and quantification of neuronal death. |
Reaction Conditions | 10, 30, 100μM; 10, 12 days |
Applications | Moclobemide (10-100μM) included in the culture medium during anoxia or with glutamate significantly increased in a concentration-dependent manner the amount of surviving neurons compared to controls. |
| Animal experiment [2]: | |
Animal models | Chronically stressed mice |
Preparation Method | Mice were randomly divided into three groups according to their body weights as normal control, chronic stress control, and stress+Moclobemide (40mg/kg, i.p.) group respectively. Moclobemide was injected daily 30min before each stressor and the control group received only water injections daily. Stressors were administered alternately one per day over a period 24d between 8:30 AM to 10:30 AM. The following seven stressors were used: cold swim (10ºC) for 6min; overhang for 30min; foot shock (1mA, 1-s duration, average 1 shock/min) for 30min; water deprivation for 24h; tail pinch (1cm apart from the end of the tail) for 1min; food deprivation for 24h; and high speed horizontal shaking for 45min. For BrdU labeling, mice were administered BrdU 4d after the last drug and stressor treatment. Twenty-four hours after the last BrdU injection, mice were killed and transcardially perfused (cold saline for 5min following by 4% cold paraform aldehyde for 15min). After perfusion, all brains were post-fixed overnight in paraformaldehyde at 4ºC and stored at 4ºC in 30% sucrose. Serial sections of the brains were cut (30µm sections) through the entire hippocampus on a freezing microtome, and sections were stored at -20ºC. The BrdU-positive cells in dentate gyrus were detected by immunohistochemistry. |
Dosage form | 40mg/kg; i.p. |
Applications | In chronically stressed mice, the BrdU-positive cells in subgranule zone of hippocampus were reduced, or even disappeared compared with the normal control. While chronic treatment with Moclobemide could reverse these changes and increase the number of BrdU-positive cells in subgranule zone significantly, indicating that Moclobemide up-regulated the proliferation of hippocampal progenitor cells. |
References: | |
| Cas No. | 71320-77-9 | SDF | |
| 别名 | 吗氯贝胺; Ro111163 | ||
| 化学名 | 4-chloro-N-(2-morpholin-4-ylethyl)benzamide | ||
| Canonical SMILES | C1COCCN1CCNC(=O)C2=CC=C(C=C2)Cl | ||
| 分子式 | C13H17ClN2O2 | 分子量 | 268.74 |
| 溶解度 | ≥ 9.85 mg/mL in DMSO, ≥ 48.3 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7211 mL | 18.6053 mL | 37.2107 mL |
| 5 mM | 744.2 μL | 3.7211 mL | 7.4421 mL |
| 10 mM | 372.1 μL | 1.8605 mL | 3.7211 mL |
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