PD05-09 EFFECTS OF SUNOBINOP (V117957) IN A MODEL OF ACUTE CYSTITIS INDUCED BY CYCLOPHOSPHAMIDE

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD05-09 EFFECTS OF SUNOBINOP (V117957) IN A MODEL OF ACUTE CYSTITIS INDUCED BY CYCLOPHOSPHAMIDE Garth Whiteside, Stamford, CT, Celine Auge, and Philippe Lluel Garth WhitesideGarth Whiteside More articles by this author , Stamford Stamford More articles by this author , CT CT More articles by this author , Celine AugeCeline Auge More articles by this author , and Philippe LluelPhilippe Lluel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial Cystitis (IC) is a chronic urological disorder characterized by pain urinary urgency, frequency and nocturia. Not all patients are responsive to existing treatments which are also limited by side-effects. As such new treatments with novel mechanisms of action are needed. Sunobinop (V117957) is a selective partial agonist of the nociceptin/orphanin-FQ (N/OFQ) peptide receptor which is excreted unchanged by the kidneys. The objective of these studies was to examine the effect of sunobinop on visceral pain in a model of interstitial cystitis in female rats. METHODS: Female Sprague-Dawley rats (10/group) were administered sunobinop (30 mg/kg, p.o.), ibuprofen (300 mg/kg, p.o.) or vehicle and 5 minutes later a single dose of cyclophosphamide (CYP; 150 mg/kg i.p). Tactile sensitivity (von Frey fibers) was measured at baseline, 2, 3, 4 and 24 hr after CYP. Parameters analyzed were nociceptive threshold (g), nociceptive scores (%) and area under the nociception curve (AUC) across two fiber ranges (1-6 g and 6-26 g) all of which were expressed as mean±standard error of the mean (SEM) with significance set at p≤0.05. RESULTS: At all evaluated time points CYP induced a significant decrease of nociception measures as compared to saline (p<0.0001) indicating successful model development. Ibuprofen-treated rats displayed a significant overall increase in nociceptive thresholds and significantly decreased nociceptive scores and AUC measures as compared to vehicle (p<0.0001). Post hoc statistical analysis showed a slight and gradual decrease of ibuprofen effect was observed over time. Sunobinop produced an overall inhibitory effect on nociceptive thresholds (significant at 3 hr), a significant decrease in nociceptive scores and a significant decrease in AUCs starting from 2h and up to 24h after CYP injection (p<0.01). After 3h, efficacy of sunobinop decreased slightly and gradually over time. CONCLUSIONS: The positive control, ibuprofen, significantly decreased pain responses, as compared to vehicle in an acute model of CYP induced IC. Likewise, sunobinop was significantly anti-nociceptive. As such this data suggests sunobinop has potential utility in treatment of pain associated with IC. Source of Funding: Imbrium Therapeutics L.P. a subsidiary of Purdue Pharmaceuticals L.P. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e152 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Garth Whiteside More articles by this author Stamford More articles by this author CT More articles by this author Celine Auge More articles by this author Philippe Lluel More articles by this author Expand All Advertisement PDF downloadLoading ...