Laropiprant

Laropiprant
Laropiprant
Systematic (IUPAC) name
(-)-[(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
Clinical data
AHFS/Drugs.com International Drug Names
Licence data EMA:Link
Pregnancy cat.  ?
Legal status  ?
Routes Oral
Identifiers
CAS number 571170-77-9 YesY
ATC code C10AD52
(combination with niacin)
UNII G7N11T8O78 N
KEGG D08940 YesY
ChEMBL CHEMBL426559 N
Synonyms MK-0524A
Chemical data
Formula C21H19ClFNO4S 
Mol. mass 435.90 g/mol
 N(what is this?)  (verify)

Laropiprant (INN) is used in combination with niacin to reduce blood cholesterol (LDL and VLDL). Merck & Co. planned to market this combination under the trade names Cordaptive and Tredaptive. On April 28, 2008, the U.S. Food and Drug Administration (FDA) issued a "not approved" letter for Cordaptive.[1] Tredaptive was approved by the European Medicines Agency (EMA) on July 3, 2008.[2]

Laropiprant itself has no cholesterol lowering effect, but it reduces facial flushes induced by niacin. In a trial with 1613 patients, 10.2% patients stopped taking the medication in the Cordaptive group versus 22.2% under niacin monotherapy.[3]

Tredaptive contains 1000 mg of niacin and 20 mg of laropiprant in each tablet.[4]

Mechanism of action

Niacin in cholesterol lowering doses (500–2000 mg per day) causes facial flushes by stimulating biosynthesis of prostaglandin D2, especially in the skin. PG D2 acts as a vasodilator via DP1 receptors, increasing blood flow and thus leading to flushes.[4][5]

Laropiprant acts as a DP1 antagonist, reducing the vasodilation.[4]

Taking 650 mg of aspirin 20–30 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis,[6] but this medication also increases the risk of gastrointestinal bleeding,[7] though the increased risk is less than 1 percent.[8]

References

  1. ^ Carey, John (April 29, 2008). "FDA Rejects Merck's Cordaptive". BusinessWeek. http://www.businessweek.com/bwdaily/dnflash/content/apr2008/db20080429_182260.htm. Retrieved 2009-11-13. 
  2. ^ "Tredaptive European Public Assessment Report". European Medicines Agency. http://www.emea.europa.eu/humandocs/Humans/EPAR/tredaptive/tredaptive.htm. Retrieved November 13, 2009. 
  3. ^ Lai E, De Lepeleire I, Crumley TM, et al. (June 2007). "Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1". Clin. Pharmacol. Ther. 81 (6): 849–57. doi:10.1038/sj.clpt.6100180. PMID 17392721. 
  4. ^ a b c "Tredaptive Prescribing Information" (PDF). Merck & Co.. http://www.merck.com/newsroom/pdf/Tredaptive_pi.pdf. Retrieved 2009-11-14. 
  5. ^ Sood, A.; Arora, R. (2009). "Mechanisms of Flushing Due to Niacin and Abolition of These Effects". The Journal of Clinical Hypertension 11 (11): 685. doi:10.1111/j.1559-4572.2008.00050.x. PMID 19878384.  edit
  6. ^ Richard A. Kunin (1976). "The Action of Aspirin in Preventing the Niacin Flush and its Relevance to the Antischizophrenic Action of Megadose Niacin" (PDF). Orthomolecular Psychiatry 5 (2): 89–100. http://www.orthomolecular.org/library/jom/1976/pdf/1976-v05n02-p089.pdf. Retrieved 2009-11-14. 
  7. ^ Sørensen HT, Mellemkjaer L, Blot WJ, et al. (September 2000). "Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin". Am. J. Gastroenterol. 95 (9): 2218–24. doi:10.1111/j.1572-0241.2000.02248.x. PMID 11007221. 
  8. ^ [1][dead link]

Wikimedia Foundation. 2010.

Игры ⚽ Нужно решить контрольную?

Look at other dictionaries:

  • Laropiprant — Strukturformel Allgemeines Freiname Laropiprant Andere Namen …   Deutsch Wikipedia

  • Niacin — IUPAC name …   Wikipedia

  • Merck & Co. — Merck Co., Inc. (Merck Sharp Dohme (MSD) outside the United States and Canada) Type Public Traded as NYSE:  …   Wikipedia

  • Statin — This article is about the group of cholesterol lowering drugs. For the amino acid, see Statine. Lovastatin, a compound isolated from Aspergillus terreus, was the first statin to be marketed. Statins (or HMG CoA reductase inhibitors) are a class… …   Wikipedia

  • Hypolipidemic agent — Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of hyperlipidemias. They are called lipid lowering drugs (LLD) or agents. Contents 1 Classes of hypolipidemic drugs 1.1… …   Wikipedia

  • Simvastatin — Systematic (IUPAC) name …   Wikipedia

  • Fluvastatin — Systematic (IUPAC) name (3R,5S,6E) 7 [3 (4 fluorophenyl) 1 (propan 2 yl) 1H indol 2 yl] 3,5 dihydroxyhept 6 enoic acid Clinical data Trade names Lescol …   Wikipedia

  • Rosuvastatin — Systematic (IUPAC) name …   Wikipedia

  • Pravastatin — Systematic (IUPAC) name (3R,5R) 3,5 dihydroxy 7 ((1R,2S,6S,8R,8aR) 6 hydroxy 2 methyl 8 {[(2S) 2 methylbutanoyl]oxy} 1,2,6,7,8,8a hexahydronaphthalen 1 yl) heptanoic acid …   Wikipedia

  • Lovastatin — Systematic (IUPAC) name (1S,3R,7S,8S …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”