PMC

NKB antagonists docking on tiTac3Ra: Predicted docking of NKB antagonists Osanetant, Talnetant, and SB-222200.

Inhibition of responses to colo-rectal distension in conscious rats by the selective NK₃ receptor antagonists talnetant and SB-235375 (). The effects of isobaric colo-rectal distension were assessed by measuring the number of abdominal contractions induced by increasing pressures of distension. Talnetant (a) or SB-235345 (b) was dosed orally and the effects were compared with vehicle; n=10 each, ^*P<0.05 vs vehicle. Unlike talnetant, SB-235345 had no measurable ability to cross the rat blood–brain barrier into the brain or spinal cord (see also, ).

Chemical structures of NK3R antagonists. Chemical structures of the phenylquinoline-based NK3R antagonists talnetant (A) and M8 (B).

Schild analyses showing the non-competitive like mode of antagonism by RO4583298 at hNK₃, cmNK₃, gNK₃ and gpNK₃, and competitive antagonism by talnetant and osanetant at gNK₃. Concentration-response curves (CRCs) for [³H]-IP formation stimulated by [MePhe⁷]NKB in the absence or presence of increasing concentrations of RO4583298 (A, B, C and D), talnetant (E) or osanetant (F) in HEK293 cells expressing transiently the hNK₃, cmNK₃, gNK₃ or gpNK₃. Each point represents mean ± SEM (bars) of six measurements from three independent transfections. Cells were incubated with antagonists for 20 min at 37°C prior to stimulation with [MePhe⁷]NKB.