title: Acute and subchronic toxicities of QX100626, a 5-HT4 receptor agonist, in rodents and Beagle dogs.
abstract: Serotonin 5-hydroxytryptamine 4(5-HT4) receptor agonists have been widely prescribed as a prokinetics drug for patients with gastro-esophageal reflux disease and functional dyspepsia. QX100626, one of the 5-HT4 receptor agonists, has been studied as a promising agent for this clinical use. The objective of the present study was to identify possible target organs of toxicity and propose a non-toxic dose of QX100626 for clinical usage. After single lethal dose oral and intravenous testing in rodents, some signs indicative of adverse CNS effects were observed. The minimum toxic dose of QX100626 for a single oral administration for dogs was 90.0mg/kgb.w., and the severe toxic dose was more than 300mg/kgb.w. The No Observed Adverse Effect Level (NOAEL) of QX100626 by daily oral administration for rats and dogs was 20mg/kg and 10mg/kg, respectively, whereas the minimum toxic dosages were 67 and 30mg/kg, respectively. All of the adverse effects suggested that kidney, digestive tract, as well as nervous, hematological, and respiratory systems might be the target organs of toxicity for humans induced by QX100626. The compound could be a safe alternative to other existing prokinetic agents for the treatment of functional bowel disorders.
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Bojun
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Dai
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Evaluation of Drug Safety, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China. Electronic address: guocailu1@163.com.
authors.forename: Guocai
authors.initials: G
authors.lastname: Lu
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D058828:Serotonin 5-HT4 Receptor Agonists / Q000008:administration & dosage / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D005765:Gastrointestinal Agents; D058828:Serotonin 5-HT4 Receptor Agonists
keywords: 5-HT(4) receptor agonist; Dyspepsia; GERT; QX100626; Safety assessment