The radioligand binding profiles and in vivo pharmacological characteristics of YM-44781, YM-44778 and YM-49598, novel non-peptide tachykinin receptor antagonists, were examined and compared to those of FK-888 and GR-159897. Since no functional NK₃ receptors were found in the rat bladder, the emphasis will be on the other two subtypes. YM-44781 and YM-49598 exhibited high binding affinities at NK₂ (pK_i = 9.94 ± 0.03) and NK₁ (pK_i = 9.09 ± 0.02) receptors, respectively, whereas YM-44778 exhibited high binding affinities at both NK₁ (pK_i = 8.08 ± 0.07) and NK₂ (pK_i = 8.55 + 0.04) receptors stably transfected in CHO-K1 cells (Chinese hamster ovary cells). In an in vivo rat model, a drug-induced bladder contraction model, antagonism of the contractions produced by the selective NK₂ receptor agonist, [βAla⁸]neurokinin A (4–10) (10 µg·kg^–1 i.v.) was observed after intravenous administration (dose range 0.001–1 mg·kg^–1) of YM-44781 and YM-44778 (IC₅₀ = 27 ± 8 and 100 ± 44 µg· kg^–1, respectively). YM-44781 was more potent (about 3-fold) than YM-44778. YM-49598 was almost inactive but produced a potent inhibition (IC₅₀ = 11 ± 7 µg·kg^–1) of the contraction of the rat urinary bladder induced by challenge with the NK₁-selective receptor agonist [Sar⁹,Met(O₂)¹¹]substance P sulphone (0.3 µg·kg^–1). YM-44781 and YM-44778 did not produce major inhibition of [Sar⁹,Met(O₂)¹¹]substance P-induced bladder contraction. These findings indicate that YM-44781 and YM-49598 are potent NK₂ and NK₁ receptor antagonists, respectively, whereas YM-44778 is a nonselective NK₂/NK₁ receptor antagonist in the drug-induced bladder contraction model.