title: Effects of OPC-51803, a novel, nonpeptide vasopressin V2-receptor agonist, on micturition frequency in Brattleboro and aged rats.
abstract: We assessed the effects of OPC-51803 ((5R)-2-[1-(2-chloro-4-(1-pyrrolidinyl)benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]-N-isopropylacetamide), a nonpeptide vasopressin V(2)-receptor agonist, on micturition frequency in female homozygous Brattleboro rats (strain carries hereditary diabetes insipidus) and aged male Sprague-Dawley rats with polyuria. Female homozygous Brattleboro rats exhibited more diuresis and a larger micturition frequency over a 24-h period than did the heterozygous controls. In Brattleboro rats, an oral administration of OPC-51803 at 0.03 and 0.3 mg/kg significantly decreased urinary frequency and was accompanied by decreased urine volume. However, little effect was seen in the mean and maximal micturition volume. Aged male Sprague-Dawley rats (25-month-old) showed a significant increase in urine volume throughout a 0- to 24-h period compared with mature (6-month-old) rats. Orally administered OPC-51803 at 0.3 mg/kg decreased not only urine volume but also urinary frequency in aged rats. Furthermore, OPC-51803 prolonged the time prior to the first micturition. Therefore, OPC-51803 decreased micturition frequency in both rat species by reducing urine outflow. This suggests that the compound will be useful for treating micturition disorders that result in frequent micturition, such as that from polyuria, nocturnal polyuria, and some kinds of urinary incontinence.
authors.affiliation: First Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan. s_nakamura@research.otsuka.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Shuji
authors.initials: S
authors.lastname: Itoh
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kondo
authors.forename: Toyoki
authors.initials: T
authors.lastname: Mori
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kambe
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists*; D013045:Species Specificity; D013997:Time Factors; D014554:Urination / Q000187:drug effects*
chemical_list: D001552:Benzazepines; C409942:OPC 51803; D011759:Pyrrolidines; D017483:Receptors, Vasopressin