Centhaquin
(Synonyms: Centhaquine; PMZ-2010) 目录号 : GC39357
Centhaquin (Centhaquine, PMZ-2010), a potential agent for treatment of haemorrhagic shock, can augment cardiac output, reduce systemic vascular resistance in haemorrhagic models.
Cas No.:57961-90-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Centhaquin (Centhaquine, PMZ-2010), a potential agent for treatment of haemorrhagic shock, can augment cardiac output, reduce systemic vascular resistance in haemorrhagic models.
[1] Srimal RC, et al. Pharmacol Res. 1990 May-Jun;22(3):319-29. [2] Papalexopoulou K, et al. Heart Lung Circ. 2017 Aug;26(8):856-863.
| Cas No. | 57961-90-7 | SDF | |
| 别名 | Centhaquine; PMZ-2010 | ||
| Canonical SMILES | CC1=CC=CC(N(CC2)CCN2CCC3=NC4=C(C=CC=C4)C=C3)=C1 | ||
| 分子式 | C22H25N3 | 分子量 | 331.45 |
| 溶解度 | DMSO: 62.5 mg/mL (188.57 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 | 3.017 mL | 15.0852 mL | 30.1705 mL |
| 5 mM | 0.6034 mL | 3.017 mL | 6.0341 mL |
| 10 mM | 0.3017 mL | 1.5085 mL | 3.017 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。
Centhaquin improves survival in a swine model of hemorrhagic shock
J Surg Res 2016 Jan;200(1):227-35.PMID:26216751DOI:10.1016/j.jss.2015.06.056.
Background: Hemorrhage is a frequent event in hospital and prehospital settings. The aim of the present study was to investigate whether Centhaquin improves 24-h survival and reduces the total volume of required fluids in an established model of swine hemorrhagic shock. Material and methods: Twenty-five pigs were instrumented and subjected to hemorrhagic shock. The animals were randomly allocated in two experimental groups, the control (vehicle) (n = 10) and the Centhaquin groups (0.015 mg/kg, n = 10); all animals received lactated Ringer solution in the resuscitation phase until their mean arterial pressure reached 90% of the baseline. A sham group (n = 5) was added a posteriori to mimic the hemodynamic profile of the Centhaquin group. Results: A statistically significant difference was observed in the time required for the three groups to reach their target mean aortic pressure, 36.88 ± 3.26 min for the control group versus 9.40 ± 1.01 min for the sham group and 7.10 ± 0.97 min for the Centhaquin group (P < 0.001). The total amount of fluids in the control and the sham groups was significantly higher when compared with that of the centhaquin-treated animals (P < 0.001). All 10 animals in the Centhaquin group survived for 24 h, whereas only three animals survived in the control group and one animal in the sham group (P = 0.002). Conclusions: Centhaquin 0.015 mg/kg administered in the fluid resuscitation phase resulted in lower volume of fluids and better survival compared with control and sham-operated animals.
Centhaquin antinociception in mice is mediated by α2A- and α2B- but not α2C-adrenoceptors
Eur J Pharmacol 2013 Sep 5;715(1-3):328-36.PMID:23712005DOI:10.1016/j.ejphar.2013.05.004.
The use of clonidine as a primary and adjuvant analgesic is well-documented. It is known that imidazoline and α2-adrenoceptors are involved in clonidine antinociception. Clonidine also produces antihypertensive actions mediated through the central nervous system. We have reported that Centhaquin, a centrally-acting anti-hypertensive drug produces its hypotensive effect through a mechanism of action similar to clonidine. Centhaquin has also been shown to possess significant antinociceptive activity. Centhaquin antinociception is partially blocked by yohimbine, idazoxan, and naloxone; however, the involvement of specific adrenoceptor subtypes (α2A, α2B, or α2C) in Centhaquin antinociception is unknown. The present study was conducted to determine antinociceptive properties of Centhaquin citrate, a water soluble salt of Centhaquin, and involvement of α2A-, α2B-, or α2C-adrenoceptors in Centhaquin citrate antinociception in mice. BRL-44408 (α2A-adrenoceptor antagonist), imiloxan (α2B-adrenoceptor antagonist) and JP-1302 (α2C-adrenoceptor antagonist) were used to determine the involvement of α2A-, α2B-, or α2C-adrenoceptors, respectively. Antinociceptive (tail-flick and hot-plate) latencies were determined in male Swiss-Webster mice treated with Centhaquin citrate alone and in combination with BRL-44408, imiloxan, or JP-1302. Centhaquin citrate produced significant antinociception in mice (P<0.05) which was unaffected by JP-1302 (P>0.05) but blocked by BRL-44408 (tail-flick test: 49.75% decrease, P<0.05; hot-plate test: 49.12% decrease, P<0.05) and imiloxan (tail-flick test: 46.98% decrease, P<0.05; hot-plate test: 46.42% decrease, P<0.05). This is the first report demonstrating Centhaquin citrate antinociception and its blockade by BRL-44408 and imiloxan. We conclude that α2A and α2B but not α2C adrenoceptors are involved in Centhaquin antinociception in mice.
Pharmacokinetics of Centhaquin citrate in a rat model
J Pharm Pharmacol 2016 Jan;68(1):56-62.PMID:26725913DOI:10.1111/jphp.12498.
Objective: Centhaquin citrate is a novel agent being developed for use in the treatment of haemorrhagic shock. It has decreased mortality in rat, rabbit and pig models of hypovolaemic shock compared to hypertonic saline and lactated Ringer's resuscitation. The pharmacokinetics of Centhaquin citrate have not been described to date. Methods: Sixteen male Sprague Dawley rats were given an intravenous bolus of 0.45 mg/kg Centhaquin citrate. Rats were divided into two groups; plasma concentrations were measured at five time points for each group within 24 h after administration. Competing compartmental pharmacokinetic models were assessed. The nonparametric adaptive grid function within the Pmetrics package for R was used for parameter estimation. Predicted concentrations were calculated using population median and individual Bayesian posterior parameters. Key findings: A two-compartment model of Centhaquin citrate best fit the data. Median (IQR) values for elimination coefficient (Ke), volume of distribution (V) and intercompartmental transfer rates (Kcp, Kpc) were 8.8 (5.2-12.8) h(-1), 6.4 (2.8-10.4) l, 11.9 (4.6-15.0) h(-1) and 3.7 (2.3-9.1) h(-1), respectively. Conclusion: This is the first report of the pharmacokinetic parameters of Centhaquin citrate in a rat model. Centhaquin citrate was found to have a short half-life with a large volume of distribution.
Centhaquin attenuates hyperalgesia and non-evoked guarding in a rat model of postoperative pain primarily through α2B-adrenoceptors
Eur J Pharmacol 2016 Oct 15;789:81-87.PMID:27397429DOI:10.1016/j.ejphar.2016.07.016.
Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the α2A and α2B adrenoceptors. Present study was conducted to determine the effects of Centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), α2-(atipamezole) or α2B-(imiloxan) adrenergic receptors. Postoperative pain was induced by hind paw plantar incision in male Sprague Dawley rats. Antihyperalgesic effects were determined by measurement of paw withdrawal latencies and withdrawal force, using dynamic von Frey filaments; attenuation of non-evoked guarding was measured by assigning pain scores to spontaneous behaviors. Rotarod test was used to determine motor impairment. Animals received saline, Centhaquin or antagonist plus Centhaquin. Centhaquin produced dose-dependent antihyperalgesic effect and attenuation of non-evoked guarding behavior, versus saline treated rats (P<0.05). Naloxone partially blocked while atipamezole and imiloxan significantly reversed Centhaquin's antihyperalgesic effects (P<0.05). Attenuation of non-evoked guarding behavior was also blocked, but was not statistically significant. Imiloxan produced a greater block compared to atipamezole while naloxone had no significant effect. Rotarod testing indicated that Centhaquin did not cause motor impairment. This is the first report demonstrating Centhaquin antinociception in the rat postoperative pain model. Opioid, α2 adrenergic, and particularly α2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of nonevoked guarding is mediated by α2B/α2 adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries.
Pharmacokinetics of Centhaquin citrate in a dog model
J Pharm Pharmacol 2016 Jun;68(6):803-9.PMID:27109141DOI:10.1111/jphp.12554.
Objectives: Centhaquin citrate is a novel agent that is being developed for use in the resuscitation of patients with haemorrhagic shock. While pharmacokinetics have been described in small animal models, the pharmacokinetic parameters of Centhaquin citrate in large mammals have yet to be described. Methods: Four healthy Beagle dogs (two males and two females) were given an intravenous bolus of 1.0 mg/kg Centhaquin citrate. Plasma concentrations were measured at baseline and at ten time points within 24 h after administration. Multiple compartmental models were built and compared. The nonparametric adaptive grid function within the Pmetrics package for R was used for parameter estimation. Predicted concentrations were calculated using population mean and individual Bayesian posterior parameters. Key findings: Centhaquin citrate pharmacokinetic parameters were best described using a two-compartment model. Median (IQR) values for Ke , Vc , Vp , Kcp and Kpc were 4.9 (4.4-5.2) h(-1) , 328.4 (304.0-331.9) l, 1000.6 (912.3-1042.4) l, 10.6 (10.3-11.1) h(-1) and 3.2 (2.9-3.7) h(-1) , respectively. Conclusions: Pharmacokinetic parameters of Centhaquin citrate in a large mammal have been described. A large volume of distribution and rapid elimination were observed, consistent with previous work in rats.