Your browser doesn't support javascript.
loading
Effect of ASP2205 fumarate, a novel 5-HT2C receptor agonist, on urethral closure function in rats.
Ishigami, Takao; Ueshima, Koji; Ukai, Masashi; Asai, Norio; Takamatsu, Hajime; Yokono, Masanori; Takeda, Masahiro; Masuda, Noriyuki.
Afiliación
  • Ishigami T; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan. Electronic address: takao.ishigami@astellas.com.
  • Ueshima K; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Ukai M; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Asai N; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Takamatsu H; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Yokono M; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Takeda M; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
  • Masuda N; Institute for Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
J Pharmacol Sci ; 139(4): 333-339, 2019 Apr.
Article en En | MEDLINE | ID: mdl-30871873
ABSTRACT
The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT2C receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT2C receptor, with an EC50 of 0.85 nM in the intracellular Ca2+ mobilization assay. Rat 5-HT2C receptor was also activated by ASP2205 with an EC50 of 2.5 nM. Intraduodenal administration (i.d.) of ASP2205 (0.1-1 mg/kg) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner. This ASP2205 (0.3 mg/kg i.d.)-induced LPP elevation was inhibited by SB242084 (0.3 mg/kg i.v.), a selective 5-HT2C receptor antagonist. Urethral closure responses induced by intravesical pressure loading in rats were enhanced by ASP2205 (0.3 mg/kg i.v.), which was abolished by pretreatment with SB242084 (0.3 mg/kg i.v.) and bilateral transection of the pudendal nerve. In contrast, ASP2205 (0.3 mg/kg i.v.) did not change the resting urethral pressure in rats. These results indicate that ASP2205 can enhance the pudendal nerve-mediated urethral closure reflex via the 5-HT2C receptor, resulting in the prevention of involuntary urine loss.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Presión / Reflejo / Uretra / Agonistas del Receptor de Serotonina 5-HT2 / Fumaratos Límite: Animals Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Presión / Reflejo / Uretra / Agonistas del Receptor de Serotonina 5-HT2 / Fumaratos Límite: Animals Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2019 Tipo del documento: Article