The efficacy and safety of the peripheral kappa agonist fedotozine was evaluated In a double-blind, multicenter study involving 238 patients with the irritable bowel syndrome. According to the investigators, the highest dose of fedotozine markedly reduced overall disease severity (P = 0.003) and the pain component of the symptomatic profile (P = 0.009). Clinical and laboratory safety was very good.1
In a randomized, double blind manner, the peripherally selective KOR agonist ADL 10-0101 or placebo was infused into six patients with chronic pancreatitis and ongoing abdominal pain despite mu-opioid agonist therapy. One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4 h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study.2
In a study to evaluate the analgesic efficacy and safety of peripherally-restricted and highly selective kappa opioid receptor agonist CR845 when dosed preoperatively and postoperatively in women undergoing elective laparoscopic hysterectomy, the drug was found to be safe and well-tolerated when administered perioperatively, before and/or after surgery, and patients reported higher levels of satisfaction after being treated. The incidence of opioid-related treatment-emergent adverse events was lower in patients treated than in patients treated only with placebo.3
1Dapoigny M, Abitbol JL, Fraitag B. Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study. Dig Dis Sci 1995 October;40(10):2244-9. 2Eisenach JC et al. Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis. Pain Volume 101, Issues 1–2, January 2003, Pages 89–95. 3Medve RA et al. Analgesic efficacy of the peripheral kappa opioid agonist CR845 in laparoscopic hysterectomy. Presented at the American Academy of Pain Medicine’s 31st Annual Meeting, March 19-22, 2015, National Harbor, MD.