Asenapine maleate
(Synonyms: 阿塞那平马来酸盐; Org 5222 maleate) 目录号 : GC63819
Asenapine maleate (Org 5222) is a high-affinity antagonist of serotonin, norepinephrine, dopamine and histamine receptors, used for the treatment of schizophrenia and acute mania associated with bipolar disorder.
Cas No.:85650-56-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rats: Asenapine maleate is suspended in 10% hydroxypropyl-β-cyclodextrin and administered in a volume of 1 mL/kg body weight . Rats are individually fear conditioned using electrical foot shock in a Skinner box. Animals are injected intraperitoneally (i.p.) with asenapine, clozapine, olanzapine, buspirone, or SB242084 at 30 min before freezing behaviour assessment[3]. Mice: Male ICR mice are repeatedly treated with 0.1 or 0.3mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests[4].
[1]. Stoner SC, et al. Asenapine: a clinical review of a second-generation antipsychotic. Clin Ther. 2012 May;34(5):1023-40.
[2]. Shahid M, et al. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73.
[3]. Ohyama M,et al. Asenapine reduces anxiety-related behaviours in rat conditioned fear stress model. Acta Neuropsychiatr. 2016 Dec;28(6):327-336.
[4]. Ene HM, et al. Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice. Acta Neuropsychiatr. 2016 Apr;28(2):85-91.
Asenapine maleate (Org 5222) is a high-affinity antagonist of serotonin, norepinephrine, dopamine and histamine receptors, used for the treatment of schizophrenia and acute mania associated with bipolar disorder.
Asenapine shows high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (alpha1 [8.9], alpha2A [8.9], alpha2B [9.5] and alpha2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). Asenapine has a higher affinity for 5-HT2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT6, alpha2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaves as a potent antagonist (pKB) at 5-HT1A (7.4), 5-HT1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), alpha2A (7.3), alpha2B (8.3), alpha2C (6.8) and H1 (8.4) receptors.[1]
Asenapine shows high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (alpha1 [8.9], alpha2A [8.9], alpha2B [9.5] and alpha2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). Asenapine has a higher affinity for 5-HT2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT6, alpha2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaves as a potent antagonist (pKB) at 5-HT1A (7.4), 5-HT1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), alpha2A (7.3), alpha2B (8.3), alpha2C (6.8) and H1 (8.4) receptors.[1]
[1] Shahid M, et al. J Psychopharmacol,?009, 23(1), 65-73. [2] Fr錸berg O, et al. Psychopharmacology (Berl),?008, 196(3), 417-429.
| Cas No. | 85650-56-2 | SDF | Download SDF |
| 别名 | 阿塞那平马来酸盐; Org 5222 maleate | ||
| 分子式 | C21H20ClNO5 | 分子量 | 401.84 |
| 溶解度 | DMSO : 25 mg/mL (62.21 mM; Need ultrasonic)|Water : 6.25 mg/mL (15.55 mM; Need ultrasonic and warming) | 储存条件 | 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4886 mL | 12.4428 mL | 24.8855 mL |
| 5 mM | 0.4977 mL | 2.4886 mL | 4.9771 mL |
| 10 mM | 0.2489 mL | 1.2443 mL | 2.4886 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Determination of Asenapine maleate in Pharmaceutical and Biological Matrices: A Critical Review of Analytical Techniques over the Past Decade
Crit Rev Anal Chem 2022;52(8):1755-1771.PMID:34061690DOI:10.1080/10408347.2021.1919858.
Asenapine maleate is a second-generation atypical antipsychotic agent used in the treatment of schizophrenia, a neuropsychiatric disorder. It is available as a fast-dissolving sublingual tablet to avoid extensive first-pass metabolism with higher bioavailability as compared to oral formulations. Although, the established therapeutic solutions do not sufficiently satisfy the patient's safety and efficacy needs. Thus, the core research emphasis is to investigate strategies to produce novel formulations with enhanced safety and efficacy. This necessitates the development of robust, precise, and accurate methods for quantification of Asenapine maleate in different sample matrices. Given the foregoing information, the current analysis concentrates on the different analytical techniques used to assess Asenapine maleate in bulk, pharmaceutical formulations, and biological specimens. Reverse-phase HPLC coupled with UV detection is a majorly (nearly 50% of papers investigated) used technique for the estimation of Asenapine maleate in formulations. On the other hand, for its quantification in the biological matrix, hyphenated techniques using mass spectrometry are widely used. This critical review reveals different analytical methodologies, including spectrophotometric, chromatographic, capillary electrophoresis techniques reported from 2011 to 2020, for the measurement of Asenapine maleate in various sample matrices. The information presented in this review would be useful in future research for robust analytical method development for Asenapine maleate utilizing a more scientific and risk-based approach. Also, it would aid to minimize analytical failure as well as method fine-tuning throughout the product life cycle. Further, this review may also direct scientists toward the development of methodologies for green research.
Asenapine maleate: a new drug for the treatment of schizophrenia and bipolar mania
Drugs Today (Barc) 2009 Dec;45(12):865-76.PMID:20135021DOI:10.1358/dot.2009.45.12.1421561.
Schizophrenia and bipolar disorder are serious neuropsychiatric disorders with substantial health risks for patients that result in major socioeconomic burdens on society. Current therapeutic agents fail to adequately address patient needs in terms of efficacy, tolerability and treatment-related adverse events. Consequently there is an urgent need to develop more effective and better tolerated pharmacotherapies for improved treatment of these illnesses. Asenapine maleate is a novel drug recently approved by the Food and Drug Administration for treatment of acute schizophrenia and for manic or mixed episodes of bipolar I disorder with or without psychotic features in adults. It has a unique pharmacologic profile as it targets multiple dopamine, serotonin and adrenergic receptor subtypes with variable affinities. Such drug/receptor interactions contribute to the antipsychotic and antimanic efficacy of asenapine. Asenapine was effective in animal models predictive of antipsychotic activity and clinical trials indicate that it improves the symptoms of acute schizophrenia and bipolar mania, is well tolerated and has a favorable safety profile. This monograph provides an up to date review of the preclinical and clinical profiles of asenapine, including new clinical data in patients with schizophrenia and bipolar mania.
Enhancement of the Solubility of Asenapine maleate Through the Preparation of Co-Crystals
Curr Drug Deliv 2022;19(7):788-800.PMID:34353260DOI:10.2174/1567201818666210805154345.
Background: Asenapine maleate, an anti-schizophrenic drug, is a class II drug with low solubility and high permeability. This exerts a rate-limiting effect on drug bioavailability. Objective: To improve the solubility/dissolution rate of Asenapine maleate and hence the bioavailability using the co-crystal approach. Methods: Co-crystals were prepared using the solvent evaporation method. Since the drug has Hbond acceptor count of 6, and H-bond donor count of 2, several co-formers (nicotinamide, urea, succinic, benzoic, and citric acid) were investigated in different ratios. The optimized co-crystals (drug-nicotinamide in a ratio of 1:3) were evaluated using PXRD, DSC, FTIR spectroscopy, and SEM. Additionally, in vitro dissolution and stability studies were conducted. Results: Preparation of the co-crystals was successful except when citric and benzoic acids were used. PXRD patterns showed that the co-crystals were crystalline. FTIR spectroscopy confirmed the formation of H-bond between the drug and the co-former. DSC indicated a lower melting point than that of the components followed immediately by an exothermic peak, which confirmed the formation of co-crystals. SEM showed the formation of crystals with different size and habit. The dissolution of the drug from all the prepared co-crystals was almost similar and much enhanced compared to that of the unprocessed drug. The initial dissolution of the drug from the optimized batch was much faster than that from the other co-crystals and the physical mixture with the same ratio. The optimized batch exhibited long term stability. Conclusion: Co-crystals with improved solubility/dissolution rate of Asenapine maleate were prepared successfully and were expected to enhance the bioavailability of the drug.
Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway
Biochem Biophys Res Commun 2021 May 14;553:172-179.PMID:33773140DOI:10.1016/j.bbrc.2021.03.042.
Background: Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis. Methods: Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFβ1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected. Results: After Ang II stimulation, TGFβ1, TGFβ1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFβ1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFβ1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFβ1/MAPK signaling pathway. Conclusions: This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFβ1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.
Asenapine maleate normalizes low frequency oscillatory deficits in a neurodevelopmental model of schizophrenia
Neurosci Lett 2019 Oct 15;711:134404.PMID:31356843DOI:10.1016/j.neulet.2019.134404.
Asenapine maleate (AM) is an atypical antipsychotic that, unlike many other antipsychotics, shows some efficacy in treating cognitive dysfunction in schizophrenia. Normal cognitive function has long since been associated with high frequency neuronal oscillations. However, recent research has highlighted the potential importance of low frequency oscillations. Here, the impact of AM on low frequency neural oscillatory activity was evaluated in the methylazoxymethanol acetate (MAM) rat model system used for the study schizophrenia, and the oscillatory signatures compared to those of haloperidol (HAL) and clozapine (CLZ). AM and CLZ normalized low frequency spectral power deficits in the prefrontal cortex, while HAL and AM reversed corticostriatal and corticocortical delta coherence deficits. However, only chronic AM administration normalized corticostriatal and corticocortical delta coherence deficits between 3-4 Hz. These findings support the idea that antipsychotic-induced amelioration of both delta coherence and power may be important for therapeutic efficacy in treating the cognitive deficits inherent in schizophrenia.