Kamo I, Imai S, Okanishi S, Doi T
Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 2-17-85, Jusohonmachi, Yodogawa-ku, 532-8686, Osaka, Japan.
Eur J Pharmacol. 2000 Aug 4;401(2):235-40. doi: 10.1016/s0014-2999(00)00468-4.
TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.
TAK-637（(aR,9R)-7-[3,5-双（三氟甲基）苄基]-8,9,10,11-四氢-9-甲基-5-（4-甲基苯基）-7H-[1,4]二氮杂环辛并[2,1-g][1,7]萘啶-6,13-二酮）是一种新型速激肽NK(1)受体拮抗剂，已被证明可抑制豚鼠的排尿反射。本研究的目的是阐明其在豚鼠中的作用机制。TAK-637可抑制脊髓动物中电刺激盆神经近端切断端所诱导的脊髓膀胱-膀胱反射，但对电刺激神经远端切断端所诱导的膀胱收缩无抑制作用。此外，TAK-637对器官浴中分离的膀胱肌肉条由卡巴胆碱或电场刺激所诱导的收缩无影响，而用于治疗尿频异常的药物可抑制这两种收缩。这些结果表明，TAK-637至少部分通过作用于脊髓来抑制排尿反射，其作用机制明显不同于抗毒蕈碱药物或解痉药。
