Following IV administration of a 14C-labeled prodrug of aprepitant (L-758298), which is converted rapidly and completely to aprepitant, approximately 57% of the total radioactivity is excreted in the urine and 45% in feces. No unchanged substance is excreted in urine. Structure and properties
Aprepitant is made up of a morpholine core with two substituents attached to adjacent ring carbons. These substitute groups are trifluoromethylated 1-phenylethanol and fluorophenyl group. Aprepitant also has a third substituent (triazolinone), which is joined to the morpholine ring nitrogen. It has three chiral centres very close together, which combine to produce an amino acetal arrangement. Its empirical formula is C23H21F7N4O3. Synthesis
Shortly after Merck initiated research into reducing the severity and likelihood of CINV, researchers discovered that aprepitant is effective in prevention. Researchers worked on coming up with a process to create aprepitant, and within a short period they came up with effective synthesis of the substance. This original synthesis was deemed to be workable and proved to be a crucial step in achieving commercialization; however, Merck decided that the process was not environmentally sustainable. This was due to the original synthesis requiring six steps, many of which needed dangerous chemicals such as sodium cyanide, dimethyltitanocene, and gaseous ammonia. In addition to this, for the process to be effective cryogenic temperatures were needed for some of the steps and other steps produced hazardous byproducts such as methane.
Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and dexamethasone. It is taken by mouth or administered by intravenous injection.Common side effects include tiredness, loss of appetite, diarrhea, abdominal pain, hiccups, itchiness, pneumonia, and blood pressure changes. Other severe side effects may include anaphylaxis. While use in pregnancy does not appear to be harmful, such use has not been well studied. Aprepitant belongs to the class of neurokinin-1 receptor antagonists medications. It works by blocking substance P from attaching to the NK1 receptors.Aprepitant was approved for medical use in the European Union and the United States in 2003. It is made by Merck & Co. It is on the World Health Organizations List of Essential Medicines. Medical uses
Aprepitant is used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and dexamethasone. Mechanism of action
Aprepitant is classified as an NK1 antagonist because it blocks signals given off by NK1 receptors. This, therefore, decreases the likelihood of vomiting in patients. NK1 is a G protein-coupled receptor located in the central and peripheral nervous system. This receptor has a dominant ligand known as Substance P (SP). SP is a neuropeptide, composed of 11 amino acids, which sends impulses and messages from the brain.