Intestinal effect of morphine 6-glucuronide: in vivo and in vitro characterization.
Morphine 6-glucuronide, a major metabolite of morphine with potent analgesic actions, is a potent inhibitor of intestinal motility when administered to rats by the intracerebroventricular (i.c.v.) route. Morphine 6-glucuronide was 62-fold more active than morphine in inhibiting gastrointestinal transit, whereas it was only 25-fold more potent in abolishing intestinal migrating myoelectric complexes. Pretreatment with naloxone (5 micrograms/rat i.c.v.) completely prevented the disappearance of migrating myoelectric complexes induced by the morphine metabolite. In contrast, in the guinea pig ileum bioassay, morphine 6-glucuronide and morphine inhibited the electrically evoked contractions of the tissue with similar potency, although in the guinea pig ileum binding assay the metabolite showed 4-fold lower affinity for the opiate receptor. The low naloxone Ke values against morphine 6-glucuronide or morphine indicated that the action of both drugs in guinea pig ileum was mediated by mu-opioid receptors.
Massi
P
P
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Giagnoni
G
G
Basilico
L
L
Gori
E
E
Rubino
T
T
Parolaro
D
D
D000818:Animals; D001665:Binding Sites; D004347:Drug Interactions; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism
D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; D009270:Naloxone; C035349:morphine-6-glucuronide