Effect of TAK-637, a tachykinin NK1-receptor antagonist, on lower urinary tract function in cats.
The effect of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H[1,4]diazocino[2,1g][1,7]naphthyridine-6,13-dione), a tachykinin NK1-receptor antagonist, on lower urinary tract function was investigated in cats. TAK-637 (0.1, 0.3, 1 and 3 mg/kg, i.v.) produced a dose-dependent increase in bladder capacity without any significant reduction in voiding efficiency in decerebrate cats. The maximal increase in bladder capacity was 94%. By contrast, oxybutynin at 1 and 3 mg/kg (i.v.) produced a 18% and 35% increase in bladder capacity, respectively, with a 47% and 45% reduction in voiding efficiency. TAK-637 (3 mg/kg, i.v.) did not inhibit the micturition reflex induced by electrical stimulation of the rostral brainstem near the locus coeruleus, indicating that it does not impair the well-organized micturition reflex (bladder contraction and urethral relaxation). These results suggest that TAK-637 increases bladder storage capability without inhibiting the voiding function of the lower urinary tract, presumably by inhibiting the afferent pathway of the micturition reflex, rather than the efferent pathway.
Kamo
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Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Osaka, Japan. Kamo_Izumi@takeda.co.jp
Doi
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D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D009287:Naphthyridines / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D014521:Urethra / Q000187:drug effects* / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*; D014554:Urination / Q000187:drug effects
D009287:Naphthyridines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C403052:TAK 637