Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig

The effects of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,1 1-tetrahydro-9-methyl-5-(4-merhylphenyl)-7H-[1,4]diazocino[2, 1-g][1,7]naph thyridine-6,13-dione), a novel tachykinin NK, receptor antagonist, on the m icturition reflex in guinea pigs were studied in comparison with those of a nti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0. 03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethan e-anesthetized guinea pigs, but they decreased voiding pressure, although t he effect of propiverine was not statistically significant. A structurally unique tachykinin NK, receptor antagonist, (+/-)-CP-99,994 ((+/-)-(2S,3S)-3 -(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a mini mum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the vo lume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanest hetized guinea pigs. These results indicate that TAK-637 may be useful as p harmacotherapy for detrusor overactivity without decreasing voiding pressur e or causing voiding difficulties. (C) 1999 Elsevier Science B.V. All right s reserved.