Guanabenz
(Synonyms: GBZ, GA, Wytensin, Wy-8678,BR-750) 目录号 : GC25484Guanabenz (GBZ, GA, Wytensin, Wy-8678,BR-750) is an orally active central alpha 2-adrenoceptor (α2 adrenergic receptor) agonist with antihypertensive action.
Cas No.:5051-62-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Guanabenz (GBZ, GA, Wytensin, Wy-8678,BR-750) is an orally active central alpha 2-adrenoceptor (α2 adrenergic receptor) agonist with antihypertensive action.
Interleukin-6 (IL6), colony stimulating factor 2 (Csf2), and cyclooxygenase-2 (Cox2) are downregulated by guanabenz-driven phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Although expression of IL1β and Tumor Necrosis Factor-α (TNFα) was suppressed by guanabenz, their downregulation was not directly mediated by eIF2α signaling.[2]
[1] B Holmes, et al. Drugs. 1983 Sep;26(3):212-29. [2] Takigawa S, et al. Int J Mol Sci. 2016 May 5;17(5):674.
| Cas No. | 5051-62-7 | SDF | Download SDF |
| 别名 | GBZ, GA, Wytensin, Wy-8678,BR-750 | ||
| 分子式 | C8H8Cl2N4 | 分子量 | 231.08 |
| 溶解度 | DMSO: 12 mg/mL (51.93 mM);Water: Insoluble;Ethanol: 15 mg/mL (64.91 mM) | 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 | 4.3275 mL | 21.6375 mL | 43.2751 mL |
| 5 mM | 0.8655 mL | 4.3275 mL | 8.655 mL |
| 10 mM | 0.4328 mL | 2.1638 mL | 4.3275 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。
Guanabenz-an old drug with a potential to decrease obesity
Naunyn Schmiedebergs Arch Pharmacol 2022 Aug;395(8):963-974.PMID:35511242DOI:10.1007/s00210-022-02251-1.
The aim of this study was to determine, in the diet-induced obesity model in rats, the potential of Guanabenz to reduce body weight and ameliorate some metabolic disturbances. Obesity was induced in rats by a high-fat diet. After 10 weeks, rats were treated intraperitoneally with Guanabenz at the two doses: 2 or 5 mg/kg b.w./day, once daily for 25 days. The spontaneous activity of rats was measured for 24 h on the 1st and 24th day of the Guanabenz treatment with a special radio-frequency identification system. Gastric emptying was measured in intragastric phenol red-treated mice by measuring the color of the stomach homogenate 30 min after phenol red administration. Intraperitoneal administration of Guanabenz for 25 days to obese rats resulted in a significant decrease in body weight compared to the baseline values (about 11% at a dose of 5 mg/kg). Both body weight and the amount of adipose tissue in the groups receiving Guanabenz decreased to the levels observed in the control rats fed only standard feed. The anorectic effect occurred in parallel with a reduction in plasma triglyceride levels. We also confirmed the beneficial effect of Guanabenz on plasma glucose level. The present study demonstrates that the administration of Guanabenz strongly inhibits gastric emptying (about 80% at a dose of 5 mg/kg). Guanabenz can successfully and simultaneously attenuate all the disorders and risk factors of metabolic syndrome: hypertension, hyperglycemia, obesity, and dyslipidemia. However, the exact cellular mechanisms of its action require further research.
Guanabenz. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension
Drugs 1983 Sep;26(3):212-29.PMID:6352237DOI:10.2165/00003495-198326030-00003.
Guanabenz is an orally active central alpha 2-adrenoceptor agonist. Its antihypertensive action is thought to result from a decrease in sympathetic outflow from the brain to the peripheral circulatory system as a result of stimulation of central alpha 2-adrenoceptors. In mild to moderate hypertension it is as effective as methyldopa and clonidine in lowering blood pressure when used as the sole treatment. As with these drugs, Guanabenz may be combined with a diuretic to increase its blood pressure-lowering effect. The overall incidence of side effects seen with Guanabenz was at least as high as with methyldopa or clonidine, and side effects such as drowsiness or dry mouth have been bothersome enough to lead to discontinuation of Guanabenz therapy in some patients. However, particularly troublesome effects such as sodium retention, depression or sexual dysfunction which may occur with methyldopa or clonidine have not been reported with Guanabenz.
Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1
Ann Clin Transl Neurol 2022 Aug;9(8):1147-1162.PMID:35778832DOI:10.1002/acn3.51611.
Objective: Vanishing white matter (VWM) is a leukodystrophy, characterized by stress-sensitive neurological deterioration and premature death. It is currently without curative treatment. It is caused by bi-allelic pathogenic variants in the genes encoding eukaryotic initiation factor 2B (eIF2B). eIF2B is essential for the regulation of the integrated stress response (ISR), a physiological response to cellular stress. Preclinical studies on VWM mouse models revealed that deregulated ISR is key in the pathophysiology of VWM and an effective treatment target. Guanabenz, an α2-adrenergic agonist, attenuates the ISR and has beneficial effects on VWM neuropathology. The current study aimed at elucidating Guanabenz's disease-modifying potential and mechanism of action in VWM mice. Sephin1, an ISR-modulating Guanabenz analog without α2-adrenergic agonistic properties, was included to separate effects on the ISR from α2-adrenergic effects. Methods: Wild-type and VWM mice were subjected to placebo, Guanabenz or sephin1 treatments. Effects on clinical signs, neuropathology, and ISR deregulation were determined. Guanabenz's and sephin1's ISR-modifying effects were tested in cultured cells that expressed or lacked the α2-adrenergic receptor. Results: Guanabenz improved clinical signs, neuropathological hallmarks, and ISR regulation in VWM mice, but sephin1 did not. Guanabenz's effects on the ISR in VWM mice were not replicated in cell cultures and the contribution of α2-adrenergic effects on the deregulated ISR could therefore not be assessed. Interpretation: Guanabenz proved itself as a viable treatment option for VWM. The exact mechanism through which Guanabenz exerts its ameliorating impact on VWM requires further studies. Sephin1 is not simply a Guanabenz replacement without α2-adrenergic effects.
Guanabenz and Clonidine, α2-Adrenergic Receptor Agonists, Inhibit Choroidal Neovascularization
Curr Neurovasc Res 2021;18(1):85-92.PMID:34011258DOI:10.2174/1567202618666210518133634.
Background: Neovascular age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of blindness in elderly people. Anti-vascular endothelial growth factor (anti-VEGF)-drugs are used to treat AMD patients; however, some patients are resistant to these therapies. Objective: The purpose of this study was to investigate the anti-angiogenic effects of α2-adrenergic agonists, including Guanabenz and clonidine. Methods: We evaluated the anti-angiogenic effects of α2-adrenergic agonists in human retinal microvascular endothelial cells (HRMECs). A proliferation assay was conducted, and the migration ratio was evaluated. In a laser-induced CNV model, Guanabenz and clonidine were delivered via intraperitoneal injection or implantation of an osmotic pump device. Fourteen days following CNV induction, CNV lesion size and fundus fluorescein angiography (FFA) were evaluated. Results: Guanabenz and clonidine inhibited VEGF-induced retinal endothelial cell growth and migration. In the CNV model mice, CNV lesion sizes were reduced by intraperitoneal administration of Guanabenz or clonidine. Data, including body weight, systolic blood pressure, and heart rate showed that Guanabenz (0.5 and 2.0 mg/kg/day) had little effect on these parameters; conversely, a high dose of clonidine (1.0 mg/kg/day) did affect these parameters. Additionally, clonidine did not affect CNV size, but continuous administration of Guanabenz attenuated both CNV size and leakage from neovessels. Conclusion: Our study suggests a key role for α2-adrenergic receptors during CNV formation. Therefore, we suggest that α2-adrenergic receptor agonists may represent novel therapeutic drugs for patients with neovascular AMD.
Guanabenz mitigates the neuropathological alterations and cell death in Alzheimer's disease
Cell Tissue Res 2022 May;388(2):239-258.PMID:35195784DOI:10.1007/s00441-021-03570-0.
Alzheimer's disease (AD) pathology is characterized by cognitive impairment, increased acetylcholinesterase (AChE) activity, and impaired neuronal communication. Clinically, AChE inhibitors are being used to treat AD patients; however, these remain unable to prevent the disease progression. Therefore, further development of new therapeutic molecules is required having broad spectrum effects on AD-related various neurodegenerative events. Since repurposing is a quick mode to search the therapeutic molecules; henceforth, this study was conducted to evaluate the anti-Alzheimer activity of drug Guanabenz which is already in use for the management of high blood pressure in clinics. The study was performed employing both cellular and rat models of AD along with donepezil as reference drug. Guanabenz treatment in both the experimental models showed significant protection against AD-specific behavioral and pathological indicators like AChE activity, tau phosphorylation, amyloid precursor protein, and memory retention. In conjunction, Guanabenz also attenuated the AD-related oxidative stress, impaired mitochondrial functionality (MMP, cytochrome-c translocation, ATP level, and mitochondrial complex I activity), endoplasmic reticulum stress (GRP78, GADD153, cleaved caspase-12), neuronal apoptosis (Bcl-2, Bax, cleaved caspase-3), and DNA fragmentation. In conclusion, findings suggested the panoptic protective effect of Guanabenz on disease-related multiple degenerative markers and signaling. Furthermore, clinical trial may shed light and expedite the availability of new therapeutic anti-Alzheimer's molecule for the wellbeing of AD patients.