Granisetron

Granisetron

Systematic (IUPAC) name
1-methyl-N-((1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-indazole-3-carboxamide
Clinical data
Trade names	Kytril
AHFS/Drugs.com	monograph
MedlinePlus	a601211
Pregnancy cat.	B1 (Au),
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral, intravenous, transdermal
Pharmacokinetic data
Bioavailability	60%
Protein binding	65%
Metabolism	Hepatic
Half-life	3–14 hours
Excretion	Renal 11–12%, faecal 38%
Identifiers
CAS number	109889-09-0 Y
ATC code	A04AA02
PubChem	CID 3510
IUPHAR ligand	2300
DrugBank	DB00889
ChemSpider	10482033 Y
UNII	WZG3J2MCOL Y
KEGG	D04370 Y
ChEMBL	CHEMBL519643 N
Chemical data
Formula	C18H24N4O
Mol. mass	312.41 g/mol
SMILES CN4[C@@H]1CCC[C@H]4C[C@H](C1)NC(=O)c3nn(C)c2ccccc23
InChI InChI=1S/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- Y Key:MFWNKCLOYSRHCJ-BTTYYORXSA-N Y
N (what is this?)  (verify)

Granisetron is a serotonin 5-HT₃ receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.

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.

Indications

• Chemotherapy-induced nausea and vomiting
  • 5-HT₃ receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenously about 30 minutes before beginning therapy.
• Post-operative and post-radiation nausea and vomiting
• Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis
• Treatment of Cyclic vomiting syndrome although there are no formal trials to confirm efficacy.

The proof of efficacy of granisetron to treat post-anesthetic nausea and vomiting has been questioned. Dr. Yoshitaka Fujii published 12 papers on this topic in Canadian Journal of Anesthesia which have since been retracted. A further five papers in the same journal on the same drug by Dr Fujii are considered indeterminate.

Adverse effects

Granisetron is a well-tolerated drug with few side effects. Headache, dizziness, and constipation are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver's cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

APF530

A New Drug Application (NDA) for APF530, a sustained-delivery form of Granisetron, was accepted in October 2012. APF530 will be targeted as an antiemetic, towards patients undergoing radiation therapy and chemotherapy. APF530 contains the 5-HT3 antagonist, granisetron, formulated in the Company's proprietary Biochronomer™ drug delivery system, which allows therapeutic drug levels to be maintained for five days with a single subcutaneous injection.

External links

• Kytril Web site
• Sancuso Web site

See also

• 5-HT₃ receptor antagonist: Drug discovery and development

References

• Katzung, Bertram G. Basic and Clinical Pharmacology, 9th ed. (2004). ISBN 0-07-141092-9