Dazopride (AHR-5531)
(Synonyms: 达佐必利; AHR-5531) 目录号 : GC33555
Dazopride (AHR-5531) 是一种止吐剂。
Cas No.:70181-03-2
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
Dazopride is an antiemetic agent.
Dazopride (0.3 mg/kg) produces significant enhancement of gastric evacuation and is approximately six times more potent than metoclopramide in gastric evacuation assay. Dazopride (0.3-10.0 mg/kg, i.v.) produces a dose-related increase in antral motility primarily by increasing the amplitude of antral contractions in three conscious dogs. Dazopride significantly reduces the emetic frequency from that of the control group[1]. Dazopride (5 mg/kg, i.p.) antagonises the tetralin-induced emesis in all animals, but fails to antagonise the response at 0.25-2.5 mg/kg. Dazopride fails to modify cisplatin-induced emesis at 0.1 mg/kg (i.v,) although a larger dose of 1.0 mg/kg abolishes or attenuates the response and 5.0 mg/kg of dazopride antagonises the development ofemesis in all animals[2].
[1]. Alphin RS, et al. Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility. Dig Dis Sci. 1986 May;31(5):524-9. [2]. Costall B, et al. The action of dazopride to enhance gastric emptying and block emesis. Neuropharmacology. 1987 Jul;26(7A):669-77.
| Cas No. | 70181-03-2 | SDF | |
| 别名 | 达佐必利; AHR-5531 | ||
| Canonical SMILES | O=C(NC1CN(CC)N(CC)C1)C2=CC(Cl)=C(N)C=C2OC | ||
| 分子式 | C15H23ClN4O2 | 分子量 | 326.82 |
| 溶解度 | Soluble in DMSO | 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 | 3.0598 mL | 15.2989 mL | 30.5979 mL |
| 5 mM | 0.612 mL | 3.0598 mL | 6.1196 mL |
| 10 mM | 0.306 mL | 1.5299 mL | 3.0598 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。
The action of Dazopride to enhance gastric emptying and block emesis
Neuropharmacology 1987 Jul;26(7A):669-77.PMID:3114664DOI:10.1016/0028-3908(87)90227-9.
The substituted benzamide derivatives, Dazopride and metoclopramide, enhanced field stimulation-induced contractions of guinea-pig stomach strips and gastric emptying in the guinea-pig after peripheral, intracerebroventricular and intrahypothalamic injection. In the isolated vagal nerve preparation from the rabbit, both compounds were shown to be 5-hydroxytryptamine M-receptor antagonists. Dazopride and metoclopramide were equipotent in antagonising cisplatin-induced emesis in the ferret, whereas metoclopramide was approximately 200 times more potent than Dazopride in antagonising the emesis caused by the dopamine agonist 2-di-n-propylamino-5,6-dihydroxytetralin in the marmoset. In behavioural tests which indicate dopamine receptor antagonism in the rat, metoclopramide induced catalepsy, antagonised amphetamine-induced stereotypy and the hyperactivity induced by the intrastriatal injection of dopamine, caused body asymmetry on unilateral injection into the striatum and also antagonised apomorphine-induced climbing and circling behaviour in the mouse. In contrast, Dazopride had little or no action in these tests and failed to displace [3H]spiperone in radioligand binding assays. The use of Dazopride provides evidence to dissociate a dopamine receptor blockade from an ability to facilitate gastric emptying and to antagonise cisplatin-emesis, and indicates that antagonism of 5-hydroxytryptamine M-receptors is the essential basis of action for Dazopride and plays an important role in the actions of metoclopramide.
Emesis induced by cisplatin in the ferret as a model for the detection of anti-emetic drugs
Neuropharmacology 1987 Sep;26(9):1321-6.PMID:2890117DOI:10.1016/0028-3908(87)90094-3.
The intravenous injection of cisplatin in the ferret caused a consistent emetic (vomiting/retching) response. Emesis induced by cisplatin was abolished by the 5-hydroxytryptamine (5-HT) M-receptor antagonists ICS205-930, zacopride, Dazopride and metoclopramide. The neuroleptic agents haloperidol, fluphenazine, domperidone, sulpiride and tiapride also antagonized emesis induced by cisplatin but only a proportion of the animals were completely protected and diazepam and prednisolone only reduced the intensity of the response. It is concluded that compounds used in the clinic to antagonise emesis induced by chemotherapy are effective in the ferret model. Antagonism of emesis induced by cisplatin in the ferret was most potently achieved by the use of the 5-HT M-receptor antagonists ICS205-930 and zacopride. However, an antagonism of dopamine receptors would appear relevant to the anti-emetic effects of the neuroleptic agents and may contribute to the anti-emetic effects of metoclopramide. Diazepam and prednisolone exert their modest antagonism by unknown mechanisms. The use of the 5-HT M-receptor antagonists is revealed as a novel approach to the treatment of emesis induced by cisplatin.
Dose-ranging evaluation of the substituted benzamide Dazopride when used as an antiemetic in patients receiving anticancer chemotherapy
Cancer Chemother Pharmacol 1993;31(6):442-4.PMID:8453682DOI:10.1007/BF00685032.
Dazopride, a substituted benzamide structurally related to metoclopramide, is a potent gastric prokinetic agent that prevents cisplatin-induced emesis in animals. Unlike metoclopramide, Dazopride has no effect on dopamine receptors and therefore should not produce extrapyramidal side effects. In this dose-ranging trial, 23 patients with cancer receiving chemotherapy known to produce nausea and vomiting received three i.v. infusions of Dazopride every 2 h beginning 30 min before the chemotherapy. Seven dose levels were explored ranging from 0.5 to 4.0 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, visual disturbances, and headaches. All side effects were transient and were not dose-related. Antiemetic effects were observed. Dazopride can be safely given on this schedule at doses of up to 4.0 mg/kg to patients receiving chemotherapy. On the basis of the results of this trial, further studies of this agent are warranted.
Antagonism of cisplatin-induced emesis by metoclopramide and Dazopride through enhancement of gastric motility
Dig Dis Sci 1986 May;31(5):524-9.PMID:3698769DOI:10.1007/BF01320319.
The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, Dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and Dazopride. The antiemetic actions of metoclopramide and Dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.
Further characterization, by use of tryptamine and benzamide derivatives, of the putative 5-HT4 receptor mediating tachycardia in the pig
Br J Pharmacol 1991 Jan;102(1):107-12.PMID:2043916DOI:10.1111/j.1476-5381.1991.tb12140.x.
1. It has recently been shown that the tachycardic response to 5-hydroxytryptamine (5-HT) in the anaesthetized pig, being mimicked by 5-methoxytryptamine and renzapride and blocked by high doses of ICS 205-930, is mediated by the putative 5-HT4 receptor. In the present investigation we have further characterized this receptor. 2. Intravenous bolus injections of the tryptamine derivatives, 5-HT (3, 10 and 30 micrograms kg-1), 5-methoxytryptamine (3, 10 and 30 micrograms kg-1) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT; 3, 10, 30 and 100 micrograms kg-1), resulted in dose-dependent increases in heart rate of, respectively, 25 +/- 2, 48 +/- 3 and 68 +/- 3 beats min-1 (5-HT; n = 35); 15 +/- 1, 32 +/- 2 and 57 +/- 3 beats min-1 (5-methoxytryptamine; n = 30); 6 +/- 4, 18 +/- 6, 34 +/- 6 and 64 +/- 11 beats min-1 (alpha-methyl-5-HT; n = 3). 3. The increases in heart rate following i.v. administration of certain substituted benzamide derivatives were genereally less marked and not dose-dependent: 1 + 5, 11 + 3 and 10 + 5 beats min1- after 300, 1000 and 3000,jgkg' of metoclopramide, respectively, (n = 8); 21 + 4, 19 + 2 and 2 + 2 beats min'- after 100, 300 and lOOOIpgkg1- of cisapride, respectively, (n = 5); 6 + 2, 14 + 2, 37 + 6, 43 + 8 and 34 + 10 beats min- after 10, 30, 100, 300 and lOOOjigkg' of zacopride, respectively, (n = 6); and 1 + 1, 2 + 1 and 5 + 2 beats min- 1 after 300, 1000 and 3000 pg kg' of Dazopride, respectively, (n = 4). These drugs behaved as partial agonists, antagonizing the responses to 5-HT and 5-methoxytryptamine dosedependently. 4. The 5-HT3 receptor agonist 1-phenyl-biguanide (100, 300 and lOOOpgkg-1) induced only slight increases in heart rate of 1 + 1, 6 + 2 and 11 + 1 beats min 1, respectively, (n = 3). These effects were not antagonized by the selective 5-HT3 receptor antagonist granisetron (3mgkg-1). In addition, 1-phenylbiguanide (1000,pg kg- 1) did not modify the tachycardia induced by either 5-HT- or 5- methoxytryptamine. 5. High doses (3mg kg- 1) of ICS 205-930, a 5-HT3 receptor antagonist with an indole group and devoid of effects on porcine heart rate per se, antagonized the stimulatory effects of 5-HT, 5-methoxytryptamine, alpha-Me-5-HT, metoclopramide, cisapride, zacopride, Dazopride and 1-phenyl-biguanide. However, the 5-HT2 receptor antagonist ketanserin (0.5 mg kg- 1), the 5-HT3 receptor antagonists granisetron (3mg kg- 1) and MDL 72222 (3mg kg- ') and the dopamine D2 receptor antagonist domperidone (3 mg kg- 1) had no antagonist activity. 6. The above results support our contention that 5-HT, 5-methoxytryptamine, alpha-Me-5-HT and the substituted benzamide derivatives increase porcine heart rate by a direct action on the cardiac pacemaker, via the activation of a putative 5-HT4 receptor. The pharmacological profile of this novel 5-HT receptor is similar (neurones from mouse brain colliculi and human heart) or, perhaps, even identical (guinea-pig cholinergic neurones) to other putative 5-HT4 receptors.