Ezlopitant

• CJ- 11974
• (2S, 3S )-2- benzhydryl -3-[ (5 -isopropyl -2- methoxybenzyl) amino] quinuclidine (IUPAC)

Antiemetic

NK1 antagonist

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Ezlopitant is a chemical compound that has been as a potential drug for the treatment of irritable bowel syndrome and to treat nausea and vomiting after cytostatics administration in cancer chemotherapy. His further clinical development by the pharmaceutical company Pfizer has been discontinued. Pharmacologically Ezlopitant is a neurokinin antagonist.

Pharmacology

Mode of action ( pharmacodynamics )

Ezlopitant as an antagonist inhibits the neurokinin NK1 receptor. It displaces the endogenous ligand substance P from its binding site on the receptor and thereby prevents the substance P mediated effects. As a NK1 receptor antagonist Ezlopitant has an anti-inflammatory, pain -inflammatory, anti -depressant and anti-emetic potential. A pain and vomiting inhibitory effect could be confirmed in animal experiments. In addition Ezlopitant showed in animal models appetite-suppressing effect. In clinical trials Ezlopitant has an efficacy in suppressing the cytostatic vomiting shown without it improves the symptoms of nausea.

Pharmacokinetics

Ezlopitant is absorbed into the systemic circulation rapidly and almost completely absorbed after oral administration. It undergoes extensive, virtually complete metabolism involving the cytochrome P450 isoenzymes CYP3A4, CYP3A5 and CYP2D6. The two major metabolites result from oxidation of the isopropyl side. The plasma half-life is approximately 13 hours Ezlopitant and including its metabolites over 100 hours. It is excreted in the form of metabolites to 60 percent of fecal and 40 percent in the urine.