In this article, we will discuss Rolapitant (Mechanism of Action). So, let’s get started.
Mechanism of Action
Rolapitant is a selective and competitive antagonist of human substance P/NK1 receptors. Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes and ion channels. Rolapitant is also active in animal models of chemotherapy-induced emesis.
NK1 Receptor Occupancy
A human Positron Emission Tomography (PET) study with rolapitant demonstrated that
rolapitant crosses the blood brain barrier and occupies brain NK1 receptors. A dose-dependent increase in mean NK1 receptor occupancy was observed in the dose range from 4.5 mg to 180 mg of rolapitant. At the 180 mg dose of rolapitant, the mean NK1 receptor occupancy was 73% in the striatum at 120 hours after a single dose administration in healthy subjects. The relationship between NK1 receptor occupancy and the clinical efficacy of rolapitant has not been
In a thorough QT study, rolapitant at doses up to four times higher than the recommended dose had no significant effects on the QT intervals.