Effects of an EP2 and EP3 Receptor Dual Agonist, ONO-8055, on a Radical Hysterectomy-Induced Underactive Bladder Model in Monkeys
| Autor: | Jun Kida, Hidekazu Matsuya, Hiroki Okada, Daisuke Wakamatsu, Hiroko Mashimo, Noritoshi Sekido |
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| Rok vydání: | 2017 |
| Předmět: |
Distigmine
Agonist medicine.medical_specialty 030219 obstetrics & reproductive medicine Urinary bladder Carbachol business.industry medicine.drug_class Urology 030232 urology & nephrology Prostanoid Underactive bladder medicine.disease 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure Neurology chemistry medicine Prostaglandin E2 Radical Hysterectomy business medicine.drug |
| Zdroj: | LUTS: Lower Urinary Tract Symptoms. 10:204-211 |
| ISSN: | 1757-5664 |
| Popis: | Objectives The objective was to develop an underactive bladder (UAB) model in primates and to evaluate the potential of prostanoid EP2 and EP3 receptor dual agonist ONO-8055 to become a therapeutic agent for UAB. Methods A surgical procedure resembling radical hysterectomy was performed on female cynomolgus monkeys. Subsequently, in vitro muscle strip studies were performed using bladder muscle strips from normal monkeys and monkeys that underwent surgery. In addition, uroflowmetric data were obtained at specified days after the surgery. To evaluate the effects of ONO-8055 and distigmine (DIS) on voiding function in the UAB monkey model, uroflowmetry was performed approximately 1 week after the surgery, before and after the cumulative intravenous administration of the compounds at 2 h intervals. Results In the bladder muscle strip studies, the responses to potassium chloride at 2 months, and carbachol and electrical field stimulation from 2 weeks decreased significantly. Voided volume (VV), maximum flow rate (Qmax), and average flow rate (Qave) decreased after surgery, while voiding time (VT) increased. In this model, ONO-8055 and DIS significantly increased VV and Qmax. DIS prolonged VT, while ONO-8055 had no effect. The results also showed that ONO-8055 increased Qave. Conclusions We developed a neurogenic UAB model in primates. As ONO-8055 improved voiding function in this model to at least the same degree as DIS, this EP2 and EP3 receptor dual agonist has the potential to be a candidate for neurogenic UAB pharmacotherapy. |
| Databáze: | OpenAIRE |
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