GRANESETRON
Granisetron
CAS: 109889-09-0
Molecular Formula: C18H24N4O
GRANESETRON - Names and Identifiers
| Name | Granisetron |
| Synonyms | BRL 43694 BRL 43964 GRANESETRON GRANISETRON Granisetron Granisetron free base GRANISETRON(FREE BASE) 1H-Indazole-3-carboxamide, 1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-, endo- 1H-Indazole-3-carboxamide, 1-methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]- |
| CAS | 109889-09-0 |
| EINECS | 686-533-5 |
| InChI | InChI=1/C18H24N4O/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23) |
GRANESETRON - Physico-chemical Properties
| Molecular Formula | C18H24N4O |
| Molar Mass | 312.41 |
| Density | 1.33±0.1 g/cm3(Predicted) |
| Boling Point | 532.0±40.0 °C(Predicted) |
| pKa | 12.34±0.20(Predicted) |
| Storage Condition | Inert atmosphere,Room Temperature |
| Physical and Chemical Properties | White to yellowish white crystalline powder, odorless, soluble in water, difficult to dissolve in methanol, very difficult to dissolve in ethanol, almost insoluble in ether. Melting Point: 290-292 °c. |
GRANESETRON - Risk and Safety
| HS Code | 2933399090 |
GRANESETRON - Nature
Open Data Verified Data
white or yellowish white crystalline powder, odorless. Soluble in water, more difficult to dissolve in methanol, very difficult to dissolve in ethanol, almost insoluble in ether. The melting point was 290-292 °c.
Last Update：2024-01-02 23:10:35
GRANESETRON - Preparation Method
Open Data Verified Data
granisetron was obtained by reacting 1-methyl -1H-indazole -3-formyl chloride with 3-amino -9-methyl -9-azabicyclo [3.3.1] Nonane. Acidification with hydrogen chloride-glycolic acid gave granisetron hydrochloride.
Last Update：2022-01-01 09:23:23
GRANESETRON - Use
Open Data Verified Data
developed by Smith Kline Beecham, USA, launched in 1991. Granisetron is a potent and highly selective 5-HT3 receptor antagonist of peripheral and central nervous system, and is one of the main anti Vomit drugs. It has a good preventive and therapeutic effect on Nausea and Vomit caused by radiotherapy, chemotherapy and surgery. Rapid onset, control of acute Vomit is better than ondansetron. For cytotoxic drugs or radiation induced Nausea and Vomit.
Last Update：2022-01-01 09:23:24
GRANESETRON - Reference Information
| antiemetic drug | granisetron is an antiemetic drug, which was introduced in the early 1990 s by the predecessor of GlaxoSmithKline, the British SmithKline Pharmaceutical Company. It is used to prevent and treat nausea and vomiting caused by chemotherapy and radiotherapy. Its antiemetic effect is 6-11 times that of ondansetron. The mechanism of action is through the blocking of 5-HT3 receptors in the upper intestinal abdominal centripetal nerve fibers and the nucleus tractus solitarius or vomiting chemoreceptor area, so as to achieve the effect of inhibiting nausea and vomiting caused by anti-tumor drugs and radiotherapy. Fig. 1 is the structural formula of granisetron |
| nausea and vomiting drugs caused by chemotherapy | chemotherapy is one of the important methods of cancer treatment. its effect is positive, but there are many adverse reactions, of which vomiting is one of the most serious adverse reactions. The purpose of antiemetic therapy is to prevent or reduce the frequency and intensity of nausea and vomiting related to chemotherapy. Early antiemetic drugs used in clinic have severe nerve center inhibition or extrapyramidal adverse reactions. Therefore, since the 1980s, a variety of highly selective 5-HT3 receptor blockers have been developed and gradually developed into mainstream drugs for the treatment of nausea and vomiting caused by chemotherapy. At present, antiemetic drugs can be divided into dopamine blockers, vomiting central inhibitors, antihistamines, corticosteroids, 5-HT3 receptor blockers, NK-1 receptor blockers, etc. Since the advent of the first generation of highly selective 5-HT3 receptor blocker ondansetron (ondansetron, Zofran), a series of 5-HT3 receptor blocker derivatives with definite curative effect and few adverse reactions have been developed and put into clinical practice, such as granisetron, tropisetron, azasetron, etc. Mechanism of action: The mechanism of chemotherapy drugs inducing nausea and vomiting is very complex, and its mechanism mainly includes the following aspects: Most cytotoxic drugs can stimulate the gastrointestinal mucosa, cause mucosal damage, and cause the mucosa, especially from the stomach to the ileal mucosa. The chromaffin cells release 5-HT, bind to 5-HT3 receptors to produce nerve impulses and pass into the vomiting center to cause vomiting; chemotherapy drugs and their metabolites stimulate and excite the vomiting center to produce vomiting; since the vomiting center is not protected by the blood-brain barrier, a variety of toxic substances in the blood can act here, and then transmit the signal to the vomiting center to cause vomiting; the vomiting center reacts to a variety of stimuli, which pass through a series of receptors (Dopamine receptors, histamine receptors, muscarinic receptors, 5-HT3 receptors) work. Most antiemetic drugs mainly act on one or more receptors. 5-HT is an important central transmitter in the human body. Its receptors are divided into 4 types and several subtypes, including 5-HT1,5-HT2, 5-HT3, 5-HT4, etc. 5-HT3 receptor blockers may inhibit the excitement of the afferent fibers of the vagus nerve by acting on the 5-HT3 receptors on the vagus nerve, and by acting on the 5-HT3 receptors on the AP and NTS, It inhibits the excitement of the two, blocks the afferent impulse to the vomiting center, and inhibits vomiting. Mechanism of NK-1 receptor blockers: Substance P and its receptor are new targets for studying chemotherapy-induced nausea and vomiting. Substance P is a polypeptide containing 11 amino acids, which belongs to tachykinin (tachykinin) family together with neurokinin A(NKA) and neurokinin B(NKB). There are 3 subtypes of receptors in this family (I. e. NK-1 receptor, NK-2 receptor and NK-3 receptor). Substance P mainly exists in the central nervous system and gastrointestinal tract, and has the strongest binding force with NK-1 receptors. Some experiments have proved that intravenous injection of substance P can cause vomiting, and the application of selective NK-1 receptor blockers can block vomiting caused by cytotoxic chemotherapy drugs. Arepitant (aprepitant): Arepitant is often used in combination with other antiemetic drugs. It can only be used to prevent nausea and vomiting caused by anticancer drugs, but it is not effective for existing nausea and vomiting symptoms. Clinical studies have found that the combined application of NK-1 receptor blocker aprepitant and 5-HT3 receptor blocker and dexamethasone increases the control rate of acute vomiting by 20% and the control rate of delayed vomiting by 30% ~ 40%. There is no drug resistance in aprepitant in the later course of treatment. Phase III clinical trials of aprepitant have shown that high-dose cisplatin-based chemotherapy, oral aprepitant (125mg on day 1 and 80mg on days 2-3) plus endanisetron and dexamethasone are more effective than endanisetron and dexamethasone for acute and delayed vomiting, and are well tolerated. Casopitant: The latest clinical data of the NK-1 receptor blocker casopitant( GW679769) developed by GlaxoSmithKline for indications of nausea and vomiting show that the efficacy of casopitant is better than that of ondansetron, and when combined with ondansetron, the efficacy is equivalent to that of aprepitant. A total of 1200 patients in the United States participated in 2 dose-range phase II clinical trials showing that casopitant can be effectively used for moderate and severe emetic chemotherapy. In the moderate emetic chemotherapy test, patients with 150mg casopitant plus dexamethasone and ondansetron 85% produce complete response, while patients with only dexamethasone and ondansetron 70% effective (P corticosteroid mechanism of action: glucocorticoids have multiple physiological effects. Animal experiments have found that glucocorticoids can enhance the activity of 5-HT3 receptor blockers. A large number of studies have shown that corticosteroids can increase the effective rate of preventing nausea and vomiting caused by chemotherapy. It may be through anti-inflammatory and antitoxin effects, Reduce the damage of peripheral nerves and maintain normal gastrointestinal motility, thereby reducing slow vomiting; some researchers believe that dexamethasone inhibits the production and release of 5-HT through both peripheral and central pathways; it may also be that dexamethasone improves the permeability of the blood-brain barrier to serum proteins, reduces the concentration of 5-HT in the blood on the chemoreceptor trigger area in the posterior region of the brain pole, and reduces brain tissue edema. Dexamethasone: Dexamethasone is often used as the first choice for the treatment of nausea and vomiting. Studies have shown that the combination of dexamethasone and granisetron can significantly enhance the anti-vomiting effect with few adverse reactions. |
| pharmacokinetics | this product is widely distributed in vivo, and the serum protein binding rate is about 65%. Its metabolic pathway is mainly conjugated after N-alkylation and aromatic epoxidation. Mainly excreted through urine and feces. |
| adverse reactions | human studies show that this product is well tolerated. As with other similar drugs, the common adverse reactions are only headache and constipation, but most of them are mild to moderate. There are occasional allergic reactions, and some are severe (such as anaphylactic shock). Other allergic reactions include a slight rash. In clinical trials, liver transaminases were also found to be transient, but still within the normal range. |
| taboo | 1. those who are allergic to this product. 2. Patients with gastrointestinal obstruction. |
| precautions | 1. the injection preparation of this product can be diluted with normal saline and 5% glucose injection, and should be prepared and used now. the diluted injection shall be stored in dark and room temperature for no more than 24 hours. 2. This product injection should not be mixed with other drugs after administration. 3. The daily dose of this product for patients with uncontrolled hypertension should not exceed 10mg, so as not to cause further increase of blood pressure. (2016-01-13) |
| drug interaction | 1. dexamethasone can enhance the efficacy of this product. 2. In vitro studies have shown that ketoconazole may inhibit the metabolism of this product by acting on CYP 3A isoenzyme system, but its clinical significance is still unclear. |
| Production method | 1-methyl-1H-indazole-3-formyl chloride and 3-amino-9-methyl-9-azabicyclo [3.3.1] nonane, that is, Deglasetron. Acidizing with hydrogen chloride-glycolic acid to obtain granisetron hydrochloride. |
Last Update：2024-04-09 21:32:03
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Product Name: Granisetron Visit Supplier Webpage Request for quotationCAS: 109889-09-0
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: Granisetron Visit Supplier Webpage Request for quotationCAS: 109889-09-0
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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