Medroxalol
(Synonyms: RMI81968) 目录号 : GC65874
Medroxalol (RMI81968) 是一种具有口服活性的肾上腺素受体拮抗剂，可阻断 α- 和 β- 肾上腺素受体。Medroxalol 具有抗高血压和血管扩张的活性。
Cas No.:56290-94-9
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
Medroxalol (RMI81968) is an orally active adrenergic receptor antagonist, blocks α- and β-adrenergic receptors. Medroxalol shows antihypertensive and vasodilating effects[1].
Medroxalol (0.1-10 μM; 20 min) shows α- and β-adrenergic receptor antagonism in isolated rabbit aortic strip[1].
Cell Viability Assay[1]
| Cell Line: | Isolated rabbit aortic strip |
| Concentration: | 0.1-10 μM |
| Incubation Time: | 20 min |
| Result: | Showed pA2 values of 6.09 and 7.73 for α-adrenergic receptors and β-adrenergic receptors, respevtively. |
Medroxalol (oral gavage; 12.5-50 mg/kg; once daily; 12 d) treatment shows antihypertensive activity in spontaneously hypertensive rats[1].
| Animal Model: | Male spontaneously hypertensive rats (SHR)[1] |
| Dosage: | 12.5, 25, or 50 mg/kg |
| Administration: | Oral gavage; 12.5, 25, or 50 mg/kg; once daily; 12 days |
| Result: | Produced a dose-related fall in blood pressure. |
| Cas No. | 56290-94-9 | SDF | Download SDF |
| 别名 | RMI81968 | ||
| 分子式 | C20H24N2O5 | 分子量 | 372.41 |
| 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 | 2.6852 mL | 13.4261 mL | 26.8521 mL |
| 5 mM | 0.537 mL | 2.6852 mL | 5.3704 mL |
| 10 mM | 0.2685 mL | 1.3426 mL | 2.6852 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。
Induction of uterine leiomyomas in mice by Medroxalol and prevention by propranolol
Toxicol Pathol 1987;15(4):468-73.PMID:3432948DOI:10.1177/019262338701500412.
Medroxalol hydrochloride is an antihypertensive agent with beta 1 adrenergic cardiac blocking properties, and beta 2 and some alpha 1 vasodilating activity. In previous carcinogenicity studies Medroxalol was shown to induce leiomyomas of the uterus in CD-1 mice but not in Long Evans rats. In addition, there was a significant increase in endometrial stromal sarcomas in mice receiving the lowest dose of Medroxalol; however, the lack of a dose response made the relationship to treatment questionable. Because of these findings, additional 18-month drug diet studies were conducted in 3 parallel segments using female CD-1 mice to determine the effects of: 1) an expanded range of doses, 2) various durations of dosing, and 3) the effect of the beta-blocker, propranolol, on leiomyoma induction. These studies confirmed the fact that chronic dietary treatment with Medroxalol can lead to an increased incidence of leiomyomas in the mouse uterus, but failed to demonstrate any relationship between endometrial stromal sarcomas and Medroxalol administration. A linear trend occurred in the incidence of leiomyomas and of smooth muscle hypertrophy/hyperplasia, a possible precursor to leiomyoma. Both findings were notably increased at 250 mg/kg/day or more. Doses of 50 mg/kg/day or less were considered no effect levels. At 500 mg/kg/day a treatment period of 12 months or more was required before a noticeable increase in leiomyomas occurred in mice examined after 18 months. The beta-blocker, propranolol, prevented this increase in leiomyomas, and led to the conclusion that the beta 2 agonist activity of Medroxalol was involved in their induction. Propranolol did not block the spontaneous occurrence of these tumors.
Analysis of the hypotensive effects of Medroxalol and its enantiomers, MDL 17,330A and MDL 17,331A
Clin Exp Hypertens A 1984;6(3):659-84.PMID:6144408DOI:10.3109/10641968409044029.
Medroxalol and two of its enantiomers (MDL 17, 330A , MDL 17, 331A ) were tested for activity at adrenergic receptors to clarify the mechanism(s) of the antihypertensive action of Medroxalol . The potency order for blocking postsynaptic alpha 1-receptors in vivo in rats was similar to that reported in vitro. However, relatively high doses of these compounds were necessary to block alpha 1-receptors in vivo compared to their antihypertensive doses. Postsynaptic alpha 2-receptors were not blocked by Medroxalol in vitro. Propranolol pretreatment of rats to block vascular beta 2-receptors antagonized much of the hypotensive response to Medroxalol and its enantioners , most extensively with MDL 17, 330A , but much less with MDL 17, 331A . The potency rank order as beta 2-adrenergic agonists was the same as previously reported for these compounds as beta 1-adrenergic receptor antagonists. The stimulation of beta 2-adrenergic receptors in vascular smooth muscle appears to be an important factor in the hypotensive action of Medroxalol .
Intravenous Medroxalol stimulates prolactin secretion in normal and hypertensive subjects
Clin Pharmacol Ther 1987 Jul;42(1):76-81.PMID:3595069DOI:10.1038/clpt.1987.111.
This study evaluated the effects of Medroxalol on prolactin secretion. Twelve normal subjects received Medroxalol, 1 mg/kg, intravenously and on a separate occasion, 5% dextrose in water. Integrated prolactin secretion during the 3 hours after Medroxalol injection was significantly increased as compared with dextrose (P less than 0.001). Intravenous administration of Medroxalol, 2 mg/kg, to 10 hypertensive subjects resulted in significant elevation of mean prolactin levels above basal levels at all time intervals measured from 30 to 240 minutes after injection. Oral Medroxalol administration to 11 hypertensive subjects for up to 15 months did not alter mean prolactin levels. Medroxalol neither stimulated prolactin release nor decreased dopamine suppression of prolactin release from pituitary cell cultures. In conclusion, intravenous Medroxalol stimulates prolactin secretion in both normal and hypertensive subjects. This effect is not likely mediated by a direct action of the drug on the pituitary but rather by an effect either within the central nervous system or of a drug metabolite.
Comparison of the clinical pharmacokinetics and concentration-effect relationships for Medroxalol and labetalol
Br J Clin Pharmacol 1984 May;17(5):573-8.PMID:6145441DOI:10.1111/j.1365-2125.1984.tb02392.x.
The pharmacokinetics of Medroxalol are described in normal subjects and compared with those of labetalol. Both drugs were administered in doses of 400 mg orally and 1 mg/kg intravenously. The data for both drugs was most appropriately described by a two compartment model. For oral Medroxalol the clinical pharmacokinetic parameters were a terminal elimination half-life (t 1/2,Z) of 15.6 h, a peak level of 450 ng/ml and a time to peak of 2-3 h. Following intravenous Medroxalol the bioavailability was calculated as 64%, the plasma clearance was 948 ml/min and the t 1/2,Z was 7.3 h. The t 1/2,Z following intravenous administration was significantly shorter than that following oral administration. The significant differences between Medroxalol and labetalol were in time to peak, respectively 2.3 and 1.1 h; oral t 1/2,Z, 15.6 and 5.5 h; clearance 948 and 1560 ml/min; and bioavailability, 64 and 20%. Despite the pharmacokinetic differences a similar plasma concentration-hypotensive effect relationship was described for each drug.
Medroxalol combined with hydrochlorothiazide in the treatment of hypertension
J Clin Pharmacol 1983 Oct;23(10):419-27.PMID:6139390DOI:10.1002/j.1552-4604.1983.tb01785.x.
The antihypertensive effect and safety of hydrochlorothiazide administration as a single drug and together with Medroxalol were determined in 20 patients with primary hypertension. Following two biweekly intervals on placebo and hydrochlorothiazide, Medroxalol was started at 100 mg three times a day and titrated against blood pressure response up to a maximum of 300 mg three times a day. In nine patients the effect of the single and the combined drug therapy on blood pressure during isometric handgrip exercise, on plasma renin activity, and on plasma catecholamines and their deaminated metabolites was investigated. The administration of hydrochlorothiazide was associated with a significant decrease in blood pressure, but heart rate did not change. The addition of Medroxalol produced a substantial decrease in blood pressure and heart rate in both the recumbent and upright positions (P less than 0.001). Due to careful titration of Medroxalol, orthostatic hypotension was observed only in one patient. Neither hydrochlorothiazide alone nor the combined drug regimen prevented or diminished the rise in blood pressure with exercise. Although plasma renin activity decreased during the combined drug therapy, there was no correlation between the initial levels or the change in plasma renin activity and the extent of decrease in blood pressure. The concentration of plasma epinephrine increased during the combined drug period, whereas catecholamine metabolites increased significantly during both periods of the study. It is concluded that Medroxalol combined with hydrochlorothiazide constituted a potent and safe antihypertensive therapy for the duration of the present study.