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Chemistry

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Also known as: 135729-61-2, (-)-palonosetron, Aloxi, Palonosetron [inn], Aloxi (tn), Palonosetron, (3as, 3s)-
Molecular Formula
C19H24N2O
Molecular Weight
296.4  g/mol
InChI Key
CPZBLNMUGSZIPR-NVXWUHKLSA-N
FDA UNII
5D06587D6R

Aloxireg
Isoquinoline and quinuclidine derivative that acts as a 5-HT3 RECEPTOR antagonist. It is used in the prevention of nausea and vomiting induced by cytotoxic chemotherapy, and for the prevention of post-operative nausea and vomiting.
Palonosetron is a Serotonin-3 Receptor Antagonist. The mechanism of action of palonosetron is as a Serotonin 3 Receptor Antagonist.
1 2D Structure

Aloxireg

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(3aS)-2-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3H-benzo[de]isoquinolin-1-one
2.1.2 InChI
InChI=1S/C19H24N2O/c22-19-16-6-2-4-14-3-1-5-15(18(14)16)11-21(19)17-12-20-9-7-13(17)8-10-20/h2,4,6,13,15,17H,1,3,5,7-12H2/t15-,17-/m1/s1
2.1.3 InChI Key
CPZBLNMUGSZIPR-NVXWUHKLSA-N
2.1.4 Canonical SMILES
C1CC2CN(C(=O)C3=CC=CC(=C23)C1)C4CN5CCC4CC5
2.1.5 Isomeric SMILES
C1C[C@@H]2CN(C(=O)C3=CC=CC(=C23)C1)[C@@H]4CN5CCC4CC5
2.2 Other Identifiers
2.2.1 UNII
5D06587D6R
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 2-(1-azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1h-benz(de)isoquinolin-1-one

2. 2-qhbiqo

3. Aloxi

4. Palonosetron Hydrochloride

5. Palonosetron, (3r)-

6. Palonosetron, (r-(r*,r*))-isomer

7. Palonosetron, (r-(r*,s*))-isomer

8. Palonosetron, (s-(r*,s*))-isomer

9. Rs 25233 197

10. Rs 25233 198

11. Rs 25233-197

12. Rs 25233-198

13. Rs 25233197

14. Rs 25233198

15. Rs 25259

16. Rs 25259 197

17. Rs 25259 198

18. Rs 25259-197

19. Rs 25259-198

20. Rs 25259197

21. Rs 25259198

22. Rs-25233-197

23. Rs-25233-198

24. Rs-25259

25. Rs-25259-197

26. Rs-25259-198

27. Rs25233197

28. Rs25233198

29. Rs25259

30. Rs25259197

31. Rs25259198

2.3.2 Depositor-Supplied Synonyms

1. 135729-61-2

2. (-)-palonosetron

3. Aloxi

4. Palonosetron [inn]

5. Aloxi (tn)

6. Palonosetron, (3as, 3s)-

7. (3as)-2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3h-benzo[de]isoquinolin-1-one

8. 2-qhbiqo

9. Chebi:85161

10. Palonosetron (inn)

11. 2-(1-azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1h-benz(de)isoquinolin-1-one

12. 5d06587d6r

13. Nsc-743769

14. (3~{a}~{s})-2-[(3~{s})-1-azabicyclo[2.2.2]octan-3-yl]-3~{a},4,5,6-tetrahydro-3~{h}-benzo[de]isoquinolin-1-one

15. (3as)-2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-2,3,3a,4,5,6-hexahydro-1h-benzo[de]isoquinolin-1-one

16. Palonosetronum

17. Unii-5d06587d6r

18. 149653-99-6

19. Palonosetron; Aloxi

20. Palonosetron [mi]

21. Schembl3746

22. Palonosetron [vandf]

23. (s-(r*,r*))-2-(1-azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1h-benz(de)isoquinolin-1-one

24. Palonosetron [who-dd]

25. Gtpl7486

26. Chembl1189679

27. Dtxsid5048342

28. Schembl13391549

29. (s)-2-((s)-quinuclidin-3-yl)-2,3,3a,4,5,6-hexahydro-1h-benzo[de]isoquinolin-1-one

30. Hms3886a22

31. Bcp07225

32. Hy-a0018

33. Zinc3795819

34. Bdbm50417287

35. Mfcd07783848

36. S5740

37. Akos015967749

38. Akos025311243

39. Cs-0385

40. Db00377

41. Nsc 743769

42. Ncgc00271490-05

43. As-35217

44. P-226

45. D07175

46. Ab00698542-05

47. Ab00698542_07

48. 653p996

49. Q-100993

50. Z2216208607

51. (3as)-2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3h-benzo[de]isoquinolin-1-one.

52. (5s)-3-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-azatricyclo[7.3.1.0^{5,13}]trideca-1(12),9(13),10-trien-2-one

53. 1021481-16-2

54. 1h-benz(de)isoquinolin-1-one, 2-(1-azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-, (s-(r*,r*))-

55. 1h-benz(de)isoquinolin-1-one, 2-(3s)-1-azabicyclo(2.2.2)oct-3-yl-2,3,3a,4,5,6-hexahydro-, (3as)-

2.4 Create Date
2005-08-09
3 Chemical and Physical Properties
Molecular Weight 296.4 g/mol
Molecular Formula C19H24N2O
XLogP32.8
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count1
Exact Mass296.188863393 g/mol
Monoisotopic Mass296.188863393 g/mol
Topological Polar Surface Area23.6 Ų
Heavy Atom Count22
Formal Charge0
Complexity456
Isotope Atom Count0
Defined Atom Stereocenter Count2
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, as well as prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy. Also used for the prevention of postoperative nausea and vomiting for up to 24 hours post operation.


FDA Label


Palonosetron Accord is indicated in adults for:

- the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy,

- the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

Palonosetron Accord is indicated in paediatric patients 1 month of age and older for:

- The prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.


Palonosetron Hospira is indicated in adults for:

- the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy;

- the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

Palonosetron Hospira is indicated in paediatric patients 1 month of age and older for:

- the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.


Aloxi is indicated in adults for:

- the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy,

- the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

Aloxi is indicated in paediatric patients 1 month of age and older for:

- the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3 receptors, but has little to no affinity for other 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. It is suggested 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.


5.2 MeSH Pharmacological Classification

Antiemetics

Drugs used to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)


Serotonin 5-HT3 Receptor Antagonists

Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS. (See all compounds classified as Serotonin 5-HT3 Receptor Antagonists.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
PALONOSETRON
5.3.2 FDA UNII
5D06587D6R
5.3.3 Pharmacological Classes
Serotonin-3 Receptor Antagonist [EPC]; Serotonin 3 Receptor Antagonists [MoA]
5.4 ATC Code

A04AA05


A04AA05


A04AA05


A04AA05

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


A - Alimentary tract and metabolism

A04 - Antiemetics and antinauseants

A04A - Antiemetics and antinauseants

A04AA - Serotonin (5ht3) antagonists

A04AA05 - Palonosetron


5.5 Absorption, Distribution and Excretion

Absorption

Low oral bioavailability.


Route of Elimination

After a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine


Volume of Distribution

8.3 2.5 L/kg


Clearance

160 +/- 35 mL/h/kg


5.6 Metabolism/Metabolites

Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved.


5.7 Biological Half-Life

Approximately 40 hours


5.8 Mechanism of Action

Palonosetron is a selective serotonin 5-HT3 receptor antagonist. 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. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT3 receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.


ABOUT THIS PAGE

Aloxireg Manufacturers

A Aloxireg manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Aloxireg, including repackagers and relabelers. The FDA regulates Aloxireg manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Aloxireg API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

Aloxireg Suppliers

A Aloxireg supplier is an individual or a company that provides Aloxireg active pharmaceutical ingredient (API) or Aloxireg finished formulations upon request. The Aloxireg suppliers may include Aloxireg API manufacturers, exporters, distributors and traders.

Aloxireg GMP

Aloxireg Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Aloxireg GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Aloxireg GMP manufacturer or Aloxireg GMP API supplier for your needs.

Aloxireg CoA

A Aloxireg CoA (Certificate of Analysis) is a formal document that attests to Aloxireg's compliance with Aloxireg specifications and serves as a tool for batch-level quality control.

Aloxireg CoA mostly includes findings from lab analyses of a specific batch. For each Aloxireg CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Aloxireg may be tested according to a variety of international standards, such as European Pharmacopoeia (Aloxireg EP), Aloxireg JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Aloxireg USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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