Midaglizole
(Synonyms: (±)-DG5128 free base; DG5128 free base) 目录号 : GC67691Midaglizole ((±)-DG5128 free base, DG5128 free base) 是一种有效的 α2-adrenoceptor 拮抗剂。Midaglizole 是一种降血糖药。Midaglizole 在具有升高血压并降低血糖水平的作用。
Cas No.:66529-17-7
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
Midaglizole ((±)-DG5128 free base, DG5128 free base) is a potent α2-adrenoceptor antagonist. Midaglizole is a hypoglycemic agent. Midaglizole increases blood pressure and reduces blood glucose levels in vivo[1][2][3].
Midaglizole stimulates insulin release with the EC50 values of 200 nM, 24 µM for rat islets and MIN6 β-cell line, respectively[3].
Midaglizole (3, 30 mg/kg; i.v.) increases blood pressure in rats[1].
Midaglizole (0.2, 1, 2 mg/kg; infusion) reduces blood glucose levels in dags[2].
| Animal Model: | 290-450 g, Male Wistar rats[1] |
| Dosage: | 3, 30 mg/kg |
| Administration: | I.v. |
| Result: | Increased the blood pressure by 27 and 64 mmHg at 3, 30 mg/kg, respectively. |
| Animal Model: | Dogs[2] |
| Dosage: | 0.2, 1, 2 mg/kg |
| Administration: | Superior pancreaticoduodeneal artery infusion |
| Result: | Reduced blood glucose levels by stimulating insulin release from the pancreatic islets. |
[1]. Hirohashi M, et al. Intrinsic pressor activity of midaglizole, an alpha-2 adrenoceptor antagonist, in pithed rats. Jpn J Pharmacol. 1990 Aug;53(4):519-20.
[2]. Ohneda K, et al. Mechanism of insulin secretion by midaglizole. Diabetes Res Clin Pract. 1993 Feb;19(2):127-32.
[3]. Proks P, et al. Inhibition of recombinant K(ATP) channels by the antidiabetic agents midaglizole, LY397364 and LY389382. Eur J Pharmacol. 2002 Sep 27;452(1):11-9.
| Cas No. | 66529-17-7 | SDF | Download SDF |
| 别名 | (±)-DG5128 free base; DG5128 free base | ||
| 分子式 | C16H17N3 | 分子量 | 251.33 |
| 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 | 3.9788 mL | 19.8942 mL | 39.7883 mL |
| 5 mM | 0.7958 mL | 3.9788 mL | 7.9577 mL |
| 10 mM | 0.3979 mL | 1.9894 mL | 3.9788 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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.
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Pharmacokinetics of Midaglizole, a new hypoglycaemic agent, in healthy subjects
Biopharm Drug Dispos 1990 Nov;11(8):701-13.PMID:2271746DOI:10.1002/bdd.2510110806.
The objective of this study was to evaluate the pharmacokinetics of Midaglizole, a new orally effective hypoglycaemic agent, in healthy male subjects. In Study I, volunteers were given single oral doses of 150, 200, 300, and 500 mg of Midaglizole 20 min before breakfast. In Study II, 200 mg of Midaglizole was given 30 min after breakfast. In Study III, multiple oral administration study was carried out at a dose of 200 mg t.i.d. 20 min before meals for 7 days. The disposition of Midaglizole was adequately described by a one-compartment open model with first order absorption. It was essentially dose-dependent up to 500 mg given orally. The pharmacokinetic parameters calculated by employing this model indicated that the disposition of this drug was characterized by good absorption from the intestine, a wide distribution in the body, and a rapid excretion via the kidneys. The absorption rate of Midaglizole from the intestine was definitely slowed by the presence of food, probably due to a decrease in the rate of gastric emptying. No clinical significant accumulation of Midaglizole in the body was observed during or after multiple doses. A linear correlation was found between the area under the curve of plasma concentration of Midaglizole versus time and the area calculated from the curve of change in blood glucose level versus time after oral administration of Midaglizole.
Studies of Midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects
Diabetes 1987 Feb;36(2):216-20.PMID:3542646DOI:10.2337/diab.36.2.216.
Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a novel alpha 2-adrenoceptor antagonist. Its effects on plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) in healthy male volunteers were investigated. Volunteers received single oral administrations of Midaglizole (150-500 mg), multiple increasing oral administration on 3 separate days (150-300 mg 3 times daily), or successive daily oral administration for 1 wk (200 mg 3 times daily). The hypoglycemic action of Midaglizole was observed within 0.5-1.0 h after its administration and thereafter for 5 h. The maximum hypoglycemic effect was found 1.0-1.5 h after administration. Midaglizole decreased postprandial hyperglycemia in a dose-dependent manner. In the fasting state, Midaglizole significantly increased IRI secretion and suppressed IRG secretion. Midaglizole inhibited epinephrine-induced platelet aggregation after successive administration for 1 wk (200 mg 3 times daily). The plasma half-life of Midaglizole was only 3 h, and the drug was rapidly excreted into the urine and feces, with greater than 80% in its unchanged form, within 24 h. Midaglizole did not affect the results of any clinical or laboratory tests performed. Our data indicate that Midaglizole is a possible hypoglycemic agent. Further clinical investigations are required to confirm its effects on diabetes mellitus.
Mechanism of insulin secretion by Midaglizole
Diabetes Res Clin Pract 1993 Feb;19(2):127-32.PMID:8472627DOI:10.1016/0168-8227(93)90105-e.
Midaglizole was introduced as a hypoglycemic agent, but its insulin releasing mechanism remains unknown. In the present study, the effect of Midaglizole upon the B cell function of the pancreas was investigated, using an in situ local circulation of the canine pancreas. The graded doses of Midaglizole (0.2, 1.0 and 2.0 mg/kg) revealed a dose-related response of plasma insulin. The administration of yohimbine, a classical alpha 2-antagonist (1.11 mg/kg) revealed a similar increase in plasma insulin to that with Midaglizole of equimolar amount. During the clonidine infusion Midaglizole did not elicit any significant rise in plasma insulin, whereas yohimbine increased plasma insulin significantly. During glucagon infusion plasma insulin increased following Midaglizole infusion but not by yohimbine. The simultaneous administration of diazoxide (K-channel opener) suppressed the midaglizole-induced insulin secretion. These results obtained in the present experiments revealed a different mechanism of insulin releasing action of Midaglizole from that of yohimbine. Furthermore, the finding with diazoxide administration suggests that Midaglizole stimulates insulin release through an interaction of K(+)-channel of the pancreatic B-cell.
Initial phase II clinical studies on Midaglizole (DG-5128). A new hypoglycemic agent
Diabetes 1987 Feb;36(2):221-6.PMID:3803733DOI:10.2337/diab.36.2.221.
Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a new type of oral antidiabetic agent that has an alpha 2-adrenoceptor-antagonizing effect. As previously reported, Midaglizole reduces plasma glucose, mainly by stimulation of insulin secretion, and inhibits epinephrine-induced platelet aggregation in normal human subjects. In this study, the clinical safety and efficacy of short-term administration of Midaglizole were evaluated in 47 patients with non-insulin-dependent diabetes mellitus (NIDDM). After an observation period on diet or sulfonylurea treatment (1 patient was on insulin), patients received 150-250 mg 3 times a day of Midaglizole for 2-4 wk, (some patients continued treatment for greater than 4 wk). In 20 of the patients first treated with diet and then switched to Midaglizole treatment, fasting plasma glucose (FPG) decreased significantly from 187 +/- 10 mg/dl (mean +/- SE) to 147 +/- 13 mg/dl (P less than .05) and 120 +/- 6 mg/dl (P less than .01) 2 and 4 wk, respectively, after administration of Midaglizole. Glycosylated hemoglobin (HbA1) also decreased from 12.0 +/- 0.7 to 11.3 +/- 1.1 and 10.7 +/- 0.6% after 2 and 4 wk, respectively. In 23 of the patients whose treatment was changed from sulfonylureas to Midaglizole, FPG, and HbA1 levels were maintained at the same values obtained before administration of Midaglizole. In patients treated with Midaglizole for greater than 12 wk, FPG and HbA1 were kept at the lowered levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Midaglizole, a new hypoglycaemic drug on the electrophysiological properties of guinea-pig papillary muscle
Br J Pharmacol 1991 Jun;103(2):1556-60.PMID:1884109DOI:10.1111/j.1476-5381.1991.tb09826.x.
1. The electrophysiological effects of Midaglizole, a new oral hypoglycaemic agent which is an alpha 2-adrenoceptor antagonist, were assessed in the reserpinized ventricular myocardium of the guinea-pig. 2. Midaglizole suppressed the maximal rate of rise (Vmax) and the amplitude of action potentials (APA) of the fast and the slow responses in a concentration-dependent manner without influencing the resting potentials. 3. Voltage-dependency of the Vmax block of the action potentials by Midaglizole (10 microM) did not appear in solutions containing various concentrations of KCl. 4. It is concluded that Midaglizole has inhibitory effects on the fast Na+ and slow Ca2+ currents of the membrane independent of the blockade of myocardial alpha-adrenoceptors, and that these effects may be significant in some clinical uses of the drug.