title: Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the isolated rat colon after morphine.
abstract: The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M, intraluminally) and morphine (10(-4) M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier.
authors.affiliation: Department of Vascular Surgery, Lindenhof Hospital, Bern, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Reber
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.forename: Beatrice
authors.initials: B
authors.lastname: Flogerzi
authors.forename: Catarina
authors.initials: C
authors.lastname: Batista
authors.forename: Peter
authors.initials: P
authors.lastname: Netzer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Scheurer
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D010111:Oxymorphone / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; C518509:naloxone-3-glucuronide; D010111:Oxymorphone