Aprepitant

Aprepitant (MK-0869) is a selective and high-affinity neurokinin 1 receptor antagonist with a K_d of 86 pM. IC50 & Target:Kd: 86 pM (Neurokinin 1 receptor)^[1] In Vitro:Aprepitant decreases the metabolic activity with an estimated IC₅₀ value of 20 µM. Aprepitant induces cell-growth inhibition and G1 cell-cycle arrest. Aprepitant significantly induces apoptosis in Nalm-6 cells, and the apoptosis is mediated through caspase-3 activation. Aprepitant (20 µM) induces p53 accumulation and expression of pro-apoptotic p53 target genes^[2]. Aprepitant (1, 5, 10 µM) inhibits HIV infection in MDM from both depressed and not depressed HIV negative individuals ex vivo in a dose-dependent manner. IC₉₀ value of aprepitant is equivalent to 10 μM, and the IC₅₀ value is about 5 μM^[4]. In Vivo:Aprepitant prevents the increase of NK-1R expression induced by in vivo NHP infection with B. burgdorferi. Aprepitant treatment prevents B. burgdorferi-induced increases in CCL2 protein levels in the CSF of NHPs. Aprepitant treatment prevents B. burgdorferi-induced increases in CCL2 and CXCL13 mRNA expression in the dorsal root ganglia of NHPs, prevents B. burgdorferi-induced increases in CCL2, CXCL13, IL-17A, and IL-6 mRNA expression in the spinal cord of NHPs. Aprepitant treatment attenuates B. burgdorferi infection-induced reductions in astrocyte activity/numbers^[1]. Aprepitant (10 mg/kg, i.p.) significantly attenuates the CPP expression and locomotor activation produced by AMPH and cocaine in mice. Aprepitant does not induce significant CPP or conditioned place aversion or locomotor activation or suppression^[3]. Aprepitant (125 mg/day, p.o.) results in 1 log reduction in plasma levels of viral RNA as compared to non-treated controls^[4].