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.

Identification of the oleic acid ethanolamide (OEA) isomer cis-vaccenic acid ethanolamide (VEA) as a highly abundant 18:1 fatty acid ethanolamide in blood plasma from rats and humans

“…Among these FAEAs, especially OEA gained importance because of its role in regulating food intake pathways. OEA was reported to suppress food intake by different pathways [34][35][36] and has since been discussed as an alternative for endocannabinoid antagonists for the control of food intake [35]. The FAEAs are synthesized from foodderived fatty acids [3], the conversion of which has been described in detail for OEA in vivo [14], but not for any other C18:1 isomer.…”

A novel EI-GC/MS method for the accurate quantification of anti-aging compound oleoylethanolamine inC. elegans

“…55 However, in the simple worm model, OEA might be not directly involved in food behavior or control of food intake, 65 since we saw no obvious effect on feeding behavior in LIPL-4 overexpressing worms. Recent work from Oakes et al indicated that 2-AG and AEA are the effectors of many cannabinoid-dependent behaviors, which include feeding as well as nociception and locomotion.…”

“…55,56 We wondered whether elevated OEA could affect worm feeding behavior, which was assessed by monitoring the pharyngeal contraction rates in the transgenic genotypes. As previously shown, the control eat-2 decreased pumping rate.…”

Eating disorders: from bench to bedside and back

“…In the NST, the peripheral administration of OEA induces c‐fos transcription in specific subnuclei especially those in close contact with the AP (Romano et al . ,b).…”