WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100421
CAS#: 107007-99-8 (HCl)
Description: Granisetron hydrochloride is the hydrochloride salt of an indazole derivative with antiemetic properties. As a selective serotonin receptor antagonist, granisetron competitively blocks the action of serotonin at 5-hydroxytryptamine3 (5-HT3) receptors, resulting in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
Hodoodo Cat#: H100421
Name: Granisetron HCl
CAS#: 107007-99-8 (HCl)
Chemical Formula: C18H25ClN4O
Exact Mass: 312.20
Molecular Weight: 348.870
Elemental Analysis: C, 61.97; H, 7.22; Cl, 10.16; N, 16.06; O, 4.59
Related CAS #: 107007-99-8 (HCl) 109889-09-0 (free base)
Synonym: BRL43694; BRL-43694; BRL 43694; BRL43694A; BRL 43694A; BRL-43694A; Granisetron Hydrochloride; Granisetron HCl; GRAN; US brand: Kytril.
IUPAC/Chemical Name: 1-methyl-N-((1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-indazole-3-carboxamide hydrochloride
InChi Key: QYZRTBKYBJRGJB-WQTKJZBYSA-N
InChi Code: InChI=1S/C18H24N4O.ClH/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);1H/t12-,13+,14-;
SMILES Code: O=C(C1=NN(C)C2=C1C=CC=C2)N[C@H]3C[C@@](N4C)([H])CCC[C@@]4([H])C3.[H]Cl
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: According to http://en.wikipedia.org/wiki/Granisetron, Granisetron was developed by chemists working at the British drug company Beecham around 1988 and is available as a generic. It is produced by Roche Laboratories under the trade name Kytril. The drug was approved in the United Kingdom in 1991 and in United States in 1994 by the FDA. A granisetron transdermal patch with the trade name Sancuso was approved by the US FDA on September 12, 2008. Sancuso is manufactured by ProStrakan, Inc., a pharmaceutical company headquartered in Bedminster, NJ, with global headquarters in Scotland. Granisetron breaks down slowly, staying in the body for a long time. One dose usually lasts 4 to 9 hours and is usually administered once or twice daily. This drug is removed from the body by the liver and kidneys. DRUG DESCRIPTION KYTRIL Tablets and KYTRIL Oral Solution contain granisetron hydrochloride, an antinauseant and antiemetic agent. Chemically it is endo-N-(9-methyl-9-azabicyclo [3.3.1] non-3-yl)-1-methyl-1H-indazole-3-carboxamide hydrochloride with a molecular weight of 348.9 (312.4 free base). Its empirical formula is C18H24N4O•HCl. Granisetron hydrochloride is a white to off-white solid that is readily soluble in water and normal saline at 20°C. Tablets for Oral Administration: Each white, triangular, biconvex, film-coated KYTRIL Tablet contains 1.12 mg granisetron hydrochloride equivalent to granisetron, 1 mg. Inactive ingredients are: hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide. Oral Solution: Each 10 mL of clear, orange-colored, orange-flavored KYTRIL Oral Solution contains 2.24 mg of granisetron hydrochloride equivalent to 2 mg granisetron. Inactive ingredients: citric acid anhydrous, FD&C Yellow No. 6, orange flavor, purified water, sodium benzoate, and sorbitol. CLINICAL PHARMACOLOGY Granisetron is a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist with little or no affinity for other serotonin receptors, including 5-HT1; 5-HT1A; 5-HT1B/C; 5-HT2; for alpha1-, alpha2-, or beta-adrenoreceptors; for dopamine-D2; or for histamine-H1; benzodiazepine; picrotoxin or opioid receptors. Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy that induces vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. This evokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to 5-HT3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferret animal model, a single granisetron injection prevented vomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds. In most human studies, granisetron has had little effect on blood pressure, heart rate or ECG. No evidence of an effect on plasma prolactin or aldosterone concentrations has been found in other studies. Following single and multiple oral doses, KYTRIL Tablets slowed colonic transit in normal volunteers. However, KYTRIL had no effect on oro-cecal transit time in normal volunteers when given as a single intravenous (IV) infusion of 50 mcg/kg or 200 mcg/kg.
| Biological target: | Granisetron (Hydrochloride) (BRL 43694A) is a serotonin 5-HT3 receptor antagonist. |
| In vitro activity: | The in vitro protoscolicidal effects of tropisetron and granisetron were evalutated in E. granulosus sensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes. Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. More than 90% of the PSC exposed to granisetron exhibited evagination after 72 h. The protoscolicidal effect of granisetron was 92% after 168 h of exposure (Fig.1a). At concentrations of 150 and 50 μM, the time taken to trigger 90% evagination of the PSC was 48 and 96 h for tropisetron, 96 and 144 h for granisetron and 72 and 72 h for CsA, respectively. Exposure to granisetron and ABZSO led to 75 and 30% mortality, respectively, after 240 h (Fig.1b). In those PSC exposed to granisetron, the tegument of the scolex and soma region remained unchanged (Fig.3Bb), with regularity of the microtriches (Fig.3Bc) and smoothness of the soma region (Fig.3Bd). Parasit Vectors. 2021; 14: 197. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042905/ |
| In vivo activity: | Effect of granisetron on BBB leakiness was evaluated by immunostaining. As shown in Fig. 1, the extravasation of 10 KDa Texas-red dextran and 40 KDa FITC-dextran was significantly increased with aging (Fig. 1B). In young mice, however, dextran extravasation was very low for the low molecular weight dextran (10 KDa) and was not observed with 40 KDa dextran (Fig. 1A,F). In aged mice, compared to vehicle treatment, granisetron significantly reduced extravasation of the florescence-tagged 10 and 40 KDa dextran by 40 and 60%, respectively (Fig. 1B, ,GG and.K). On the other hand, granisetron has no significant effect on dextran extravasation in young mice (Fig. 1A, ,FF andK). To evaluate granisetron effect on an endogenous and higher molecular weight BBB permeability marker, IgG extravasation was tested (Fig. 1C–E, ,HH–J ,L). Similarly, IgG extravasation significantly increased with aging (Fig. 1D), which was significantly reduced by granisetron (Fig. 1I andL), and such effect was not observed in the young mice (Fig. 1C,HH and L) Next, the effect of granisetron on BBB integrity was evaluated in TgSwDI mouse model for AD, and consistent with the wild-type aged mice results, granisetron significantly reduced IgG extravasation by 80% (Fig. 1 E,JJ and L). Moreover, granisetron treatment significantly reduced brain levels of both the microglial marker Iba-1 by 30%, and metalloproteinase-9 (MMP-9) enzyme by 47% (Fig. 6C and F). The findings support the repurposing of granisetron as a therapeutic drug for AD (Alzheimer’s disease), and possibly other neurological diseases associated with BBB disruption. J Alzheimers Dis. 2019; 72(4): 1097–1117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183768/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 9.4 | 26.93 | |
| H2O | 52.0 | 148.90 |
The following data is based on the product molecular weight 348.87 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Al Rihani SB, Lan RS, Kaddoumi A. Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through CalmodulinDependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway. J Alzheimers Dis. 2019;72(4):1097-1117. doi: 10.3233/JAD-190849. PMID: 31683487; PMCID: PMC7183768. 2. Shiee MR, Kia EB, Zahabiun F, Naderi M, Motevaseli E, Nekoeian S, Fasihi Harandi M, Dehpour AR. In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin. Parasit Vectors. 2021 Apr 12;14(1):197. doi: 10.1186/s13071-021-04691-9. PMID: 33845889; PMCID: PMC8042905. 3. Wang J, Gong S, Wang F, Niu M, Wei G, He Z, Gu T, Jiang Y, Liu A, Chen P. Granisetron protects polymicrobial sepsis-induced acute lung injury in mice. Biochem Biophys Res Commun. 2019 Jan 22;508(4):1004-1010. doi: 10.1016/j.bbrc.2018.12.031. Epub 2018 Dec 11. PMID: 30551881 4. . Al Rihani SB, Lan RS, Kaddoumi A. Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through CalmodulinDependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway. J Alzheimers Dis. 2019;72(4):1097-1117. doi: 10.3233/JAD-190849. PMID: 31683487; PMCID: PMC7183768. |
| In vitro protocol: | 1. Al Rihani SB, Lan RS, Kaddoumi A. Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through CalmodulinDependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway. J Alzheimers Dis. 2019;72(4):1097-1117. doi: 10.3233/JAD-190849. PMID: 31683487; PMCID: PMC7183768. 2. Shiee MR, Kia EB, Zahabiun F, Naderi M, Motevaseli E, Nekoeian S, Fasihi Harandi M, Dehpour AR. In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin. Parasit Vectors. 2021 Apr 12;14(1):197. doi: 10.1186/s13071-021-04691-9. PMID: 33845889; PMCID: PMC8042905. |
| In vivo protocol: | 1. Wang J, Gong S, Wang F, Niu M, Wei G, He Z, Gu T, Jiang Y, Liu A, Chen P. Granisetron protects polymicrobial sepsis-induced acute lung injury in mice. Biochem Biophys Res Commun. 2019 Jan 22;508(4):1004-1010. doi: 10.1016/j.bbrc.2018.12.031. Epub 2018 Dec 11. PMID: 30551881. 2. Al Rihani SB, Lan RS, Kaddoumi A. Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through CalmodulinDependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway. J Alzheimers Dis. 2019;72(4):1097-1117. doi: 10.3233/JAD-190849. PMID: 31683487; PMCID: PMC7183768. |
1: Wu SJ, Xiong XZ, Lin YX, Cheng NS. Comparison of the efficacy of ondansetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis. Surg Laparosc Endosc Percutan Tech. 2013 Feb;23(1):79-87. doi: 10.1097/SLE.0b013e31827549e8. Review. PubMed PMID: 23386158.
2: Hsu ES. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics. Am J Ther. 2010 Sep-Oct;17(5):476-86. doi: 10.1097/MJT.0b013e3181ea7821. Review. PubMed PMID: 20844345.
3: Duggan ST, Curran MP. Transdermal granisetron. Drugs. 2009;69(18):2597-605. doi: 10.2165/11202780-000000000-00000. Review. PubMed PMID: 19943709.
4: Vrabel M. Is ondansetron more effective than granisetron for chemotherapy-induced nausea and vomiting? A review of comparative trials. Clin J Oncol Nurs. 2007 Dec;11(6):809-13. Review. PubMed PMID: 18063539.
5: Feyer P, Seegenschmiedt MH, Steingraeber M. Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. Review. PubMed PMID: 16044252.
6: Aapro M. Granisetron: an update on its clinical use in the management of nausea and vomiting. Oncologist. 2004;9(6):673-86. Review. PubMed PMID: 15561811.
7: Goldsmith B. First choice for radiation-induced nausea and vomiting--the efficacy and safety of granisetron. Acta Oncol. 2004 Sep;43 Suppl 15:19-22. Review. PubMed PMID: 15370626.
8: Corman SL, Skledar SJ, Ansani NT. Low-dose granisetron for postoperative nausea and vomiting prophylaxis. Ann Pharmacother. 2004 Apr;38(4):710-3. Epub 2004 Feb 24. Review. PubMed PMID: 14982978.
9: Tan M. Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. Review. PubMed PMID: 12943486.
10: Blum RA, Majumdar A, McCrea J, Busillo J, Orlowski LH, Panebianco D, Hesney M, Petty KJ, Goldberg MR, Murphy MG, Gottesdiener KM, Hustad CM, Lates C, Kraft WK, Van Buren S, Waldman SA, Greenberg HE. Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther. 2003 May;25(5):1407-19. Review. PubMed PMID: 12867217.
