9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one

• ChemBase ID: 780
• Molecular Formular: C18H19N3O
• Molecular Mass: 293.36296
• Monoisotopic Mass: 293.15281224
• SMILES: O=C1C(CCc2n(c3c(c12)cccc3)C)Cn1c(ncc1)C
• Canonical SMILES: O=C1C(CCc2c1c1ccccc1n2C)Cn1ccnc1C
• InChI: InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3
• InChIKey: FELGMEQIXOGIFQ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one
• IUPAC Traditional name: ondansetron
• Brand Name: Zofran; Zofran ODT; Zophren; Zudan; PMS-ondansetron; Ratio-ondansetron; Sandoz ondansetron; PHL-ondansetron; Novo-ondansetron; Apo-ondansetron
• Synonyms: Zofran; Ondansetron; 9-Methyl-3-((2-methyl-1H-imidazol-1-yl)methyl)-2,3-dihydro-1H-carbazol-4(9H)-one; 1,2,3,4-tetrahydro-9-methyl-3-(2-methyl-1h-imidazol-1-ylmethyl)carbazol-4-one

Database IDs

• CAS Number: 99614-02-5
• PubChem SID: 160964243; 46504819
• PubChem CID: 4595

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.385697
• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 1.3377254
• LogD (pH = 7.4): 2.1069536
• Log P: 2.349965
• Molar Refractivity: 86.7795 cm^3
• Polarizability: 34.021282 Å^3
• Polar Surface Area: 39.82 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.56
• LOG S: -3.07
• Solubility (Water): 2.48e-01 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 2.4

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Serotonin receptor

Product Information

• Purity: 95+%; 97%
• Salt Data: Free Base

DETAILS

DrugBank - DB00904

• Drug Groups: approved
• Description: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. [PubChem]
• Indication: For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Also used for the treatment of postoperative nausea and vomiting.
• Pharmacology: Ondansetron is a highly specific and selective serotonin 5-HT₃ receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serontonin 5-HT₃ 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.
• Toxicity: Low blood pressure and fainting, sudden blindness, severe constipation
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism.
• Half Life: 5.7 hours
• Protein Binding: 70%-76% (Plasma protein binding)
• Clearance: * 0.38 L/h/kg [Normal Adult Volunteers (19-40 yrs)]; * 0.32 L/h/kg [Normal Adult Volunteers (61-74 yrs)]; * 0.26 L/h/kg [Normal Adult Volunteers (>=75 yrs)]
• References: Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. [Pubmed] ; Yilmaz HL, Yildizdas RD, Sertdemir Y: Clinical trial: oral ondansetron for reducing vomiting secondary to acute gastroenteritis in children--a double-blind randomized study. Aliment Pharmacol Ther. 2010 Jan;31(1):82-91. Epub . [Pubmed] ; Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. [Pubmed] ; Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1996

Biological Activity:
Ondansetron (Zofran) is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic. Its effects are thought to be on both peripheral and central nerves. Ondansetron (Zofran) decreases the activity of the vagus nerve, which deactivates the vomiting center in the medulla oblongata, and also inhibits serotonin receptors in the chemoreceptor trigger zone. Ondansetron (Zofran) has little effect on vomiting caused by motion sickness, and does not have any effect on dopamine receptors or muscarinic receptors. The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting (CINV). Ondansetron (Zofran) is also effective in controlling post-operative nausea and vomiting (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis. Although ondansetron is highly effective, the high cost of the brand-name version had limited its use to controlling PONV and CINV.Ondansetron (Zofran) is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. Ondansetron (Zofran) is also used to treat cyclic vomiting syndrome. [1]References on Ondansetron (Zofran)[1] http://en.wikipedia.org/wiki/Ondansetron, ,

REFERENCES

• Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. Pubmed
• Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. Pubmed
• Yilmaz HL, Yildizdas RD, Sertdemir Y: Clinical trial: oral ondansetron for reducing vomiting secondary to acute gastroenteritis in children--a double-blind randomized study. Aliment Pharmacol Ther. 2010 Jan;31(1):82-91. Epub . Pubmed
• Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. Pubmed
• http://en.wikipedia.org/wiki/Ondansetron