(R)-Lanicemine
(Synonyms: (R)-拉尼西明; (R)-AZD6765) 目录号 : GC61847
(R)-Lanicemine ((R)-AZD6765) 是 Lanicemine 的低活性的 R 型异构体。Lanicemine (AZD6765) 是一种低捕获的 NMDA 受体拮抗剂，Ki 为 0.56-2.1 µM。CHO 和爪蟾卵母细胞中，IC50 分别为 4-7 µM 和 6.4 µM。具有抗抑郁作用。
Cas No.:190581-71-6
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
(R)-Lanicemine ((R)-AZD6765) is the less active R-enantiomer of Lanicemine. Lanicemine (AZD6765) is a low-trapping NMDA channel blocker (Ki of 0.56-2.1 µM for NMDA receptor; IC50s of 4-7 µM and 6.4 µM in CHO and Xenopus oocyte cells, respectively). Antidepressant effects[1].
References:
[1]. Sanacora G, et al. Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacywith minimal psychotomimetic adverse effects. Mol Psychiatry. 2014 Sep;19(9):978-85.
| Cas No. | 190581-71-6 | SDF | |
| 别名 | (R)-拉尼西明; (R)-AZD6765 | ||
| Canonical SMILES | N[C@@H](C1=CC=CC=C1)CC2=CC=CC=N2 | ||
| 分子式 | C13H14N2 | 分子量 | 198.26 |
| 溶解度 | 储存条件 | Store at -20°C | |
| 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 | 5.0439 mL | 25.2194 mL | 50.4388 mL |
| 5 mM | 1.0088 mL | 5.0439 mL | 10.0878 mL |
| 10 mM | 0.5044 mL | 2.5219 mL | 5.0439 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。
Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status
CNS Drugs 2021 May;35(5):527-543.PMID:33904154DOI:10.1007/s40263-021-00816-x.
The efficacy of standard antidepressants is limited for many patients with mood disorders such as major depressive disorder (MDD) and bipolar depression, underscoring the urgent need to develop novel therapeutics. Both clinical and preclinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders. In particular, rapid reductions in depressive symptoms have been observed in response to subanesthetic doses of the glutamatergic modulator racemic (R,S)-ketamine in individuals with mood disorders. These results have prompted investigation into other glutamatergic modulators for depression, both as monotherapy and adjunctively. Several glutamate receptor-modulating agents have been tested in proof-of-concept studies for mood disorders. This manuscript gives a brief overview of the glutamate system and its relevance to rapid antidepressant response and discusses the existing clinical evidence for glutamate receptor-modulating agents, including (1) broad glutamatergic modulators ((R,S)-ketamine, esketamine, (R)-ketamine, (2R,6R)-hydroxynorketamine [HNK], dextromethorphan, Nuedexta [a combination of dextromethorphan and quinidine], deudextromethorphan [AVP-786], axsome [AXS-05], dextromethadone [REL-1017], nitrous oxide, AZD6765, CLE100, AGN-241751); (2) glycine site modulators (D-cycloserine [DCS], NRX-101, rapastinel [GLYX-13], apimostinel [NRX-1074], sarcosine, 4-chlorokynurenine [4-Cl-KYN/AV-101]); (3) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (eliprodil [EVT-101], traxoprodil [CP-101,606], rislenemdaz [MK-0657/CERC-301]); (4) metabotropic glutamate receptor (mGluR) modulators (basimglurant, AZD2066, RG1578, TS-161); and (5) mammalian target of rapamycin complex 1 (mTORC1) activators (NV-5138). Many of these agents are still in the preliminary stages of development. Furthermore, to date, most have demonstrated relatively modest effects compared with (R,S)-ketamine and esketamine, though some have shown more favorable characteristics. Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors.
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
Sci Rep 2017 Nov 16;7(1):15725.PMID:29147024DOI:10.1038/s41598-017-16060-7.
Accumulating evidence suggests a key role of the gut-microbiota-brain axis in the antidepressant actions of certain compounds. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, showed rapid and sustained antidepressant effects in treatment-resistant depressed patients. In contrast, another NMDAR antagonist, lanicemine, did not exhibit antidepressant effects in such patients. (R)-ketamine, the (R)-enantiomer of ketamine, has rapid-acting and long-lasting antidepressant effects in rodent models of depression. Here we compared the effects of (R)-ketamine and lanicemine on depression-like phenotype and the composition of the gut microbiota in susceptible mice after chronic social defeat stress (CSDS). In behavioral tests, (R)-ketamine showed antidepressant effects in the susceptible mice, whereas lanicemine did not. The 16S ribosomal RNA gene sequencing of feces demonstrated that (R)-ketamine, but not lanicemine, significantly attenuated the altered levels of Bacteroidales, Clostridiales and Ruminococcaceae in the susceptible mice after CSDS. At the genus level, (R)-ketamine significantly attenuated the marked increase of Clostridium in the susceptible mice. In contrast, the effects of lanicemine were less potent than those of (R)-ketamine. This study suggests that the antidepressant effects of (R)-ketamine might be partly mediated by the restoration of altered compositions of the gut microbiota in a CSDS model.
Ketamine, but Not the NMDAR Antagonist Lanicemine, Increases Prefrontal Global Connectivity in Depressed Patients
Chronic Stress (Thousand Oaks) 2018 Jan-Dec;2:2470547018796102.PMID:30263977DOI:10.1177/2470547018796102.
Background: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment. Methods: Fifty-six unmedicated participants with MDD were randomized to intravenous placebo (normal saline; n = 18), ketamine (0.5mg/kg; n = 19) or lanicemine (100mg; n = 19). PFC GBCr was computed using time series from functional magnetic resonance imaging (fMRI) scans that were completed at baseline, during infusion, and 24h post-treatment. Results: Compared to placebo, ketamine significantly increased average PFC GBCr during infusion (p = 0.01) and 24h post-treatment (p = 0.02). Lanicemine had no significant effects on GBCr during infusion (p = 0.45) and 24h post-treatment (p = 0.23), compared to placebo. Average delta PFC GBCr (during minus baseline) showed a pattern of positively predicting depression improvement in participants receiving ketamine (R = 0.44; p = 0.06; d = 1.0) or lanicemine (R = 0.55; p = 0.01; d = 1.3), but not those receiving placebo (R = -0.1; p = 0.69; d = 0.02). Follow-up vertex-wise analyses showed ketamine-induced GBCr increases in the dorsolateral, dorsomedial, and frontomedial PFC during infusion, and in the dorsolateral and dorsomedial PFC 24h post-treatment (corrected p < 0.05). Exploratory vertex-wise analyses examining the relationship with depression improvement showed positive correlation with GBCr in the dorsal PFC during infusion and 24h post-treatment, but negative correlation with GBCr in the ventral PFC during infusion (uncorrected p < 0.01). Conclusions: In a randomized placebo-controlled approach, the results provide the first evidence in MDD of ketamine-induced increases in PFC GBCr during infusion, and suggests that ketamine's rapid-acting antidepressant properties are related to its acute effects on prefrontal connectivity. Overall, the study findings underscore the similarity and differences between ketamine and another N-methyl-D-aspartate receptor (NMDAR) antagonist, while proposing a pharmacoimaging paradigm for optimization of novel rapid-acting antidepressants prior to testing in costly clinical trials.
Highly efficient asymmetric bioreduction of 1-aryl-2-(azaaryl)ethanones. Chemoenzymatic synthesis of lanicemine
Org Biomol Chem 2019 Sep 21;17(35):8214-8220.PMID:31451824DOI:10.1039/c9ob01616c.
Different ketoreductases (KREDs) have been used to promote a highly selective reduction of several 1-aryl-2-(azaaryl)ethanones (azaaryl = pyridinyl, quinolin-2-yl), the corresponding secondary alcohols being obtained with very high yields and enantiomeric excesses (ee > 99%). The absolute configuration of each optically active alcohol has been assigned by means of modified Mosher and Kelly methods, two shielding effects being evaluated: (1) the Mosher phenyl ring effect on the azaaryl protons and (2) the one of the azaaryl ring on the Mosher methoxy group. In addition, the biologically active amine lanicemine has been synthesized from (R)-1-phenyl-2-(pyridin-2-yl)ethanol, thus proving the utility of the secondary alcohols here prepared.