RP-67580 was studied in rats as a mediator of substance P-induced (SP) knee pain. Rats received an inferior alveolar injection of SP followed by treatment with 20 - 200 nmol RP-67580 delivered as an inferior alveolar injection. In mouse model of trypanosomiasis RP-67580 was administered intraperitoneally at dose 2 mg/kg twice daily for 10 days.

Human A549 adenocarcinoma cells were cultured in DMEM containing 10% FBS, 100 units/ml penicillin, 100 microgram/ml streptomycin, and 2 mM glutamine. A549 cells were transfected with cDNA for Tacr1, a firefly NF-kB-luciferase reporter gene, and the Renilla luciferase plasmid pRL-TK. Cells were treated with 10^-7 M substance P (SP) 24 h after transfection, and cells were collected for luciferase assay 4 h following treatment. The NK1 inhibitor RP-67580 was added 40 min prior to SP pro-inflammatory treatment, in a range of concentrations from 10^-7 to 10^-4 M. RP-67580 exhibited a dose-dependent inhibition of NF-kB-luciferase activation by SP.