Granisetron (JAN/USAN/INN)
Basic information
- CAS
109889-09-0- Standard SMILES
CN1[C@@H]2CCC[C@H]1CC(NC(=O)c1nn(C)c3ccccc13)C2- InChIKey
MFWNKCLOYSRHCJ-AGUYFDCRSA-N- Molecular formula
- C18H24N4O
- Average molar mass
- 312.4 g/mol
- Monoisotopic mass
- 312.1950114
Overview
Granisetron is a monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 1-methyl-1H-indazole-3-carboxylic acid with the primary amino group of (3-endo)-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine. A selective 5-HT3 receptor antagonist, it is used (generally as the monohydrochloride salt) to manage nausea and vomiting caused by cancer chemotherapy and radiotherapy, and to prevent and treat postoperative nausea and vomiting. It has a role as a serotonergic antagonist and an antiemetic. It is a monocarboxylic acid amide, a member of indazoles and a tertiary amino compound.
Names & identifiers
- Preferred name
- Granisetron (JAN/USAN/INN)
- IUPAC
- 1-methyl-N-[(1R,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]indazole-3-carboxamide
- English name
- Granisetron
- Molecular formula
- C18H24N4O
- Molecular weight
- 312.41
Names & synonyms
Granisetron (JAN/USAN/INN)RefChem:1086176granisetron109889-09-0SancusoSustolexo-GranisetronKevatrilBRL-43694GranisetronumAPF5301364914-39-5
Show more names
BRL 43964GRANESETRONGranisteronGramisetronGranisetron 99%Granisetron USP/EP/BPgranisetron(base,HCl)GRANISETRON(FREE BASE)
Kytril1-methyl-N-[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]indazole-3-carboxamideGranisetron EP Impurity FAPF 530WZG3J2MCOLBRL 436941-methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamideCHEBI:5537
Database identifiers
- CAS
109889-09-0- PubChem CID
- 5284566
- DTXSID
DTXSID0023111- ChEMBL
CHEMBL1290003、CHEMBL399538- ChEBI
CHEBI:5537- UNII
- WZG3J2MCOL
Properties
Computed structural properties
- XLogP
- 2.8
- Topological polar surface area
- 50.2 Ų
- Hydrogen bond donors
- 1
- Hydrogen bond acceptors
- 3
- Rotatable bonds
- 2
- Heavy atoms
- 23
- Formal charge
- 0
- Complexity
- 442
Experimental & physicochemical properties
DrugsPharmaceuticals -> Listed in ZINC15
Human DrugsPharmaceuticals
Physicochemical properties
- Boiling point
- 532 · 532.0±40.0 °C(Predicted)
- Density
- 1.33 · 1.33±0.1 g/cm3(Predicted)
- storage temp.
- Inert atmosphere,Room Temperature
- solubility
- 25 ℃: · 25℃: DMSO
- form
- Powder
- pka
- 12.34 · 12.34±0.20(Predicted)
- color
- White to off-white
- 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)/t12-,13+,14-/i2D3
- InChIKey
- MFWNKCLOYSRHCJ-JQHPXDLNNA-N
- SMILES
- C1(C(=O)N[C@H]2C[C@@]3([H])CCC[C@@]([H])(C2)N3C)C2C=CC=CC=2N(C([2H])([2H])[2H])N=1 |&1:4,6,11,r|
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
Safety data
- hs_code
- 2933399090
- Signal word
- Warning
- Symbol(GHS)
- GHS07
- Hazard statements
- H412-H302-H319
- Precautionary statements
- P273-P501-P264-P270-P301+P312-P330-P501-P264-P280-P305+P351+P338-P337+P313P
Chemistry & industry
Pharmacology
Protein Binding65%
Pharmacodynamics
Granisetron is a selective inhibitor of type 3 serotonergic (5-HT<sub>3</sub>) receptors. Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1 , 5-HT 1A , 5-HT 1B/C , or 5-HT 2 ; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors. In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG). The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT<sub>3</sub> receptors. The serontonin 5-HT<sub>3</sub> receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Mechanism of Action
Granisetron is a potent, selective antagonist of 5-HT<sub>3</sub> receptors. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.
Biological Half-Life4-6 hours in healthy patients, 9-12 hours in cancer patients
Metabolism/Metabolites
Primarily hepatic; undergoes N -demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest that some of the metabolites may have 5-HT 3 receptor antagonist activity.
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