title: Oleoylethanolamide: a novel potential pharmacological alternative to cannabinoid antagonists for the control of appetite.
abstract: The initial pharmaceutical interest for the endocannabinoid system as a target for antiobesity therapies has been restricted by the severe adverse effects of the CB1 antagonist rimonabant. This study points at oleoylethanolamide (OEA), a monounsaturated analogue, and functional antagonist of anandamide, as a potential and safer antiobesity alternative to CB1 antagonism. Mice treated with equal doses (5 or 10 mg/kg, i.p.) of OEA or rimonabant were analyzed for the progressive expression of spontaneous behaviors (eating, grooming, rearing, locomotion, and resting) occurring during the development of satiety, according to the paradigm called behavioral satiety sequence (BSS). Both drugs reduced food (wet mash) intake to a similar extent. OEA treatment decreased eating activity within the first 30 min and caused a temporary increase of resting time that was not accompanied by any decline of horizontal, vertical and total motor activity. Besides decreasing eating activity, rimonabant caused a marked increase of the time spent grooming and decreased horizontal motor activity, alterations that might be indicative of aversive nonmotivational effects on feeding. These results support the idea that OEA suppresses appetite by stimulating satiety and that its profile of action might be predictive of safer effects in humans as a novel antiobesity treatment.
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.affiliation: Institute of Cell Biology and Neurobiology (IBCN), Italian National Research Council (CNR), Via del Fosso di Fiorano, 64-00146 Roma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Coccurello
authors.affiliation: Institute of Cell Biology and Neurobiology (IBCN), Italian National Research Council (CNR), Via del Fosso di Fiorano, 64-00146 Roma, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Giacovazzo
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bedse
authors.affiliation: Institute of Cell Biology and Neurobiology (IBCN), Italian National Research Council (CNR), Via del Fosso di Fiorano, 64-00146 Roma, Italy ; Genomnia Srl, Via Nerviano 31, Lainate, 20020 Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Moles
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001066:Appetite; D001067:Appetite Depressants / Q000008:administration & dosage*; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D000077285:Rimonabant; D016896:Treatment Outcome
chemical_list: D001067:Appetite Depressants; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; C488250:oleoylethanolamide; D000077285:Rimonabant