Effects of TAK-637, a tachykinin receptor antagonist, on the micturition reflex in guinea pigs

The effects of a new tachykinin NK, receptor antagonist, (aR,9R)-7-[3,5-bis (trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7 H-[1,4]diazocino[2,1-g][1-7]naphthyridine-6,13-dione (TAK-637), on the mict urition reflex were compared with those of drugs used for abnormally freque nt micturition or incontinence. TAK-637 showed a characteristic effect on t he distension-induced rhythmic bladder contractions in guinea pigs. The sys temic administration of TAK-637 decreased the number but not the amplitude of the distension-induced rhythmic bladder contractions. A similar effect w as observed in animals in which the spinal cord had been severed. TAK-637 a lso inhibited the micturition reflex induced by topical application of caps aicin onto the surface of bladder dome. From these results, it is concluded that TAK-637 inhibits sensory transmissions from the bladder evoked by bot h physiological and nociceptive stimuli by blocking tachykinin NK1 receptor s, possibly at the level of the spinal cord. On the other hand, the other d rugs such as oxybutynin, tolterodine, propiverine, and inaperisone showed n o effects on the frequency of the distension-induced rhythmic bladder contr actions but decreased the contraction amplitude. Therefore, TAK-637 may rep resent a new class of drugs, which would be effective for abnormally freque nt micturition without causing voiding difficulties due to decreased voidin g pressure. (C) 2000 Elsevier Science B.V. All rights reserved.