6-Hydroxydopamine hydrobromide
(Synonyms: 6-羟基多巴胺氢溴酸盐; 6-Hydroxydopamine hydrobromide; 6-OHDA hydrobromide) 目录号 : GC16267
A catecholaminergic neurotoxin
Cas No.:636-00-0
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
| Cell experiment [1]: | |
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Cell lines |
Primary nigral cells (PNCs) |
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Preparation Method |
The conditioned media were replaced with new media containing AS-IV at the final concentration indicated with or without 200 µM of 6-Hydroxydopamine hydrobromide. |
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Reaction Conditions |
200µM for 24 hours |
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Applications |
Compared with vehicle controls, exposure to 200 µM 6-Hydroxydopamine resulted in the loss of 75% of PNCs, as determined using the LDH assay. |
| Animal experiment [2]: | |
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Animal models |
Female Sprague-Dawley rats |
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Preparation Method |
The animals received a single, intrastriatal injection of 6-Hydroxydopamine hydrobromide. Twenty-five micrograms of 6-Hydroxydopamine hydrobromide, which was dissolved in 1.5 µl of normal saline with 0.2% ascorbic acid, was injected at a depth of 5.6 mm ventral to the skull at the same anterior/posterior and medial/lateral coordinates at which the cells had been injected. The injection site was chosen to be midway between the two implant sites. 6-Hydroxydopamine hydrobromide was injected over 5 min, and the needle was left in place for an additional 5 min before withdrawal of the needle. |
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Dosage form |
25 µg in 1.5 µl of normal saline with 0.2% ascorbic acid |
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Applications |
Induced neurodegeneration in the SNc by unilateral injection of 6-hydroxydopamine hydrobromide into mfb, act as 6-OHDA lesion model |
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References: [1]: Chan W S, Durairajan S S K, Lu J H, et al. Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture[J]. Neurochemistry International, 2009, 55(6): 414-422. |
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6-Hydroxydopamine hydrobromide (6-OHDA) is a structural analogue of catecholamines, dopamine and noradrenaline, and exerts its toxic effects on catecholaminergic neurons. The neurotoxin 6-hydroxydopamine continues to constitute a valuable topical tool used chiefly in modeling Parkinson's disease (PD) in the rat [1].
The classical method of intracerebral infusion of 6-Hydroxydopamine hydrobromide, involving a massive destruction of nigrostriatal dopaminergic neurons, is largely used to investigate motor and biochemical dysfunctions in Parkinson's disease [1]
6-Hydroxydopamine hydrobromide undergoes robust auto-oxidation generating cytotoxic H2O2, reactive oxygen species (ROS) and catecholamine quinones which attack endocellular nucleophilic groups [2].
Neurotoxic effects of 6-Hydroxydopamine hydrobromide occur through a two-step mechanism involving accumulation of the toxin into catecholaminergic neurons, followed by alteration of cellular homeostasis and neuronal damage. Intracellular storage of 6-Hydroxydopamine hydrobromide is mediated by the dopamine or noradrenaline membrane transporters (DAT and NAT respectively), which recognize and uptake 6-Hydroxydopamine hydrobromide due to its structural similarity with endogenous catecholamines [3]. 6-Hydroxydopamine hydrobromide is infused unilaterally in the MFB, producing a functional imbalance between the dopaminergic nigrostriatal systems and resulting in motor slowness, indicative of parkinsonian-like akinesia, and typical rotational behaviour in response to dopaminomimetic agents [4].
References:
[1]. Simola N, Morelli M, Carta A R. The 6-hydroxydopamine model of Parkinson's disease[J]. Neurotoxicity research, 2007, 11(3): 151-167.
[2]. Palumbo A, A Napolitano, P Barone and M d'Ischia (1999) Nitrite- and peroxide-dependent oxidation pathways of dopamine: 6-nitrodopamine and 6-hydroxydopamine formation as potential contributory mechanisms of oxidative stress- and nitric oxide-induced neurotoxicity in neuronal degeneration. Chem. Res. Toxicol. 12, 1213-1222.
[3]. Luthman J, A Fredriksson, E Sundstrom, G Jonsson and T.Archer (1989) Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: motor behavior and monoamine alterations at adult stage. Behav. Brain.Res. 33, 267-277.
[4]. Ungerstedt U and G Arbuthnott (1970) Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24, 485-493.
6-Hydroxydopamine hydrobromide (6-OHDA) 是儿茶酚胺、多巴胺和去甲肾上腺素的结构类似物，对儿茶酚胺能神经元发挥毒性作用。神经毒素 6-羟基多巴胺继续构成一种有价值的局部工具，主要用于模拟大鼠帕金森病 (PD) [1]。
大脑内输注 6-羟基多巴胺氢溴酸盐的经典方法涉及大量破坏黑质纹状体多巴胺能神经元，主要用于研究帕金森病的运动和生化功能障碍[1]
6-羟基多巴胺氢溴酸盐会发生强烈的自氧化，产生细胞毒性 H2O2、活性氧 (ROS) 和儿茶酚胺醌，这些物质会攻击细胞内的亲核基团 [2]。
6-羟基多巴胺氢溴酸盐的神经毒性作用通过两步机制发生，涉及毒素在儿茶酚胺能神经元中的积累，然后是细胞稳态的改变和神经元损伤。 6-羟基多巴胺氢溴酸盐的细胞内储存由多巴胺或去甲肾上腺素膜转运蛋白（分别为 DAT 和 NAT）介导，由于其与内源性儿茶酚胺的结构相似，它们识别和摄取 6-羟基多巴胺氢溴酸盐[3]。 6-羟基多巴胺氢溴酸盐被单侧注入 MFB，在多巴胺能黑质纹状体系统之间产生功能失衡，导致运动迟缓，表明帕金森样运动不能，以及对多巴胺模拟药物反应的典型旋转行为[4].
| Cas No. | 636-00-0 | SDF | |
| 别名 | 6-羟基多巴胺氢溴酸盐; 6-Hydroxydopamine hydrobromide; 6-OHDA hydrobromide | ||
| 化学名 | 5-(2-aminoethyl)benzene-1,2,4-triol hydrobromide | ||
| Canonical SMILES | OC(C(CCN)=C1)=CC(O)=C1O.Br | ||
| 分子式 | C8H11NO3.HBr | 分子量 | 250.09 |
| 溶解度 | ≥ 25mg/mL in DMSO with ultrasonic | 储存条件 | Store at 4°C,stored under nitrogen,unstable in solution, ready to use. |
| 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 | 3.9986 mL | 19.9928 mL | 39.9856 mL |
| 5 mM | 0.7997 mL | 3.9986 mL | 7.9971 mL |
| 10 mM | 0.3999 mL | 1.9993 mL | 3.9986 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。
Investigation of 6-Hydroxydopamine-induced plasma extravasation in rat skin
Eur J Pharmacol1996 Apr 22;301(1-3):151-7.PMID: 8773459DOI: 10.1016/0014-2999(96)00062-3
Perfusion of 6-Hydroxydopamine into the rat knee and trachea induces plasma extravasation, possibly by tissue-specific mechanisms involving sympathetic and sensory nerves respectively, and we aimed to identify the mediators which contribute to this response in skin. 6-Hydroxydopamine (both hydrobromide and hydrochloride salts), dose dependently increased plasma extravasation into rat dorsal skin, however, when compared to bradykinin or the tachykinin NK1 receptor agonist GR73632, high concentrations of 6-Hydroxydopamine (1-10 mumol/site) were required. The response to 6-Hydroxydopamine was not inhibited in chemically sympathectomised rats (6-Hydroxydopamine, 300 mg/kg i.p. over 7 days) but was significantly reduced by co-administration with the histamine (H1) and the 5-HT receptor antagonists mepyramine and methysergide and in skin sites pre-injected with compound 48/80 (4 micrograms, -18 h) to degranulate dermal mast cells. The response was not inhibited by co-injection of the tachykinin NK1 receptor antagonist SRI40333 or by the cyclo-oxygenase inhibitor indomethacin (5 mg kg-1 i.p., -30 min) except at the lowest dose of 6-Hydroxydopamine (1 mumol/site). We conclude that 6-Hydroxydopamine is not a potent or selective mediator of increased vascular permeability in rat skin but, at high concentrations, may induce oedema formation via release of vasoactive amines from mast cells, augmented by generation of prostaglandins.
The effect of chronic administration of buspirone on 6-Hydroxydopamine-induced catalepsy in rats
Adv Pharm Bull2012;2(1):127-31.PMID: 24312782DOI: 10.5681/apb.2012.019
Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-Hydroxydopamine (6-OHDA) and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p.) administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats.
Method: Catalepsy was induced by unilateral infusion of 6-OHDA (8 ¦̧/2 ¦̬/rat) into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days) was assessed in 6-OHDA-lesioned rats.
Result: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days) decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl)- 4-[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190), 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist.
Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD). We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.
Buspirone improves 6-Hydroxydopamine-induced catalepsy through stimulation of nigral 5-HT(1A) receptors in rats
Pharmacol Rep2010 Mar-Apr;62(2):258-64.PMID: 20508280DOI: 10.1016/s1734-1140(10)70264-4
Receptors for 5-HT(1A) are widely distributed throughout the basal ganglia, and their activation results in an inhibition of dopamine (DA) release. This study aimed to investigate the effect of buspirone, as a partial agonist of 5-HT(1A) receptors, on 6-Hydroxydopamine (6-OHDA)-induced catalepsy in male Wistar rats. Catalepsy was induced by unilateral infusion of 6-OH-DA (6 microg/2 microl/rat) into the central region of the substantia nigra pars compacta (SNc) and assayed by the bar-test method 60, 120 and 180 min after drug administration. The results demonstrated that intraperitoneal (ip) injection of buspirone at doses of 5, 7.5 and 10 mg/kg decreased catalepsy compared with the control group. In addition, intra-SNc injection of 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT; 10 microg/rat), a 5-HT(1A) receptor agonist, decreased 6-OHDA-induced catalepsy. The effects of buspirone (7.5 mg/kg, ip) and 8-OH-DPAT (10 microg/rat, intra-SNc) were abolished by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190; 10 microg/rat, intra-SNc), a 5-HT(1A) receptor antagonist. Our study indicates that buspirone improves catalepsy in a 6-OHDA-induced animal model of Parkinson's disease through activation of nigral 5-HT(1A) receptors. However, further investigations should be undertaken to clarify the exact mechanism of interaction between 5-HT(1A) and DA receptors.
Carnosic acid protects SH-SY5Y cells against 6-Hydroxydopamine-induced cell death through upregulation of parkin pathway
Neuropharmacology2016 Nov;110(Pt A):109-117.PMID: 27091487DOI: 10.1016/j.neuropharm.2016.04.017
Parkin is a Parkinson's disease (PD)-linked gene that plays an important role in the ubiquitin-proteasome system (UPS). This study explored whether carnosic acid (CA) from rosemary protects against 6-Hydroxydopamine (6-OHDA)-induced neurotoxicity via upregulation of parkin in vivo and in vitro. We found that the reduction in proteasomal activity by 6-OHDA was attenuated in SH-SY5Y cells pretreated with 1 ¦̍ CA. Immunoblots showed that CA reversed the induction of ubiquitinated protein and the reduction of PTEN-induced putative kinase 1 (PINK1) and parkin protein in 6-OHDA-treated SH-SY5Y cells and rats. Moreover, in a transgenic OW13 Caenorhabditis elegans model of PD that expresses human ¦Á-synuclein in muscle cells, CA reduced ¦Á-synuclein accumulation in a dose-dependent manner. In cells pretreated with the proteasome inhibitor MG132, CA no longer reversed the 6-OHDA-mediated induction of cleavage of caspase 3 and poly(ADP)-ribose polymerase and no longer reversed the suppression of proteasome activity. When parkin expression was silenced by use of small interfering RNA, the ability of CA to inhibit apoptosis and induce proteasomal activity was significantly reduced. The reduction in 6-OHDA-induced neurotoxicity by CA was associated with the induction of parkin, which in turn upregulated the UPS and then decreased cell death.
Intraventricular 6-Hydroxydopamine increases thyrotropin-releasing hormone (TRH) content in regions of rat brain
Regul Pept1985 Sep;12(1):51-7.PMID: 3934717DOI: 10.1016/0167-0115(85)90186-7
Rats were given intraventricular (ivt) injections of various doses (50-400 micrograms, hydrobromide salt) of 6-Hydroxydopamine (6-OHDA) and killed 1, 3 or 6 days later. Brains were removed, dissected into 11 regions, and the thyrotropin-releasing hormone (TRH) content of each region was measured by radioimmunoassay. 6-OHDA (400 micrograms) caused significant elevations in the TRH content of 6 regions: olfactory bulb, anterior cortex, brainstem, posterior cortex, hippocampus, and amygdala-piriform cortex. The magnitude of these increases ranged from 59% in olfactory bulb to 497% in hippocampus and was, in all cases, greatest at 3 days. These results suggest that the TRH content of certain brain regions may be regulated by catecholamine neurotransmitters.