title: ENP11, a potential CB1R antagonist, induces anorexia in rats.
abstract: Over the past decade, pharmacological manipulation of cannabinoid 1 receptor (CB1R) has become an interesting approach for the management of food ingestion disorders, among other physiological functions. Searching for new substances with similar desirable effects, but fewer side-effects we have synthesized a SR141716A (a cannabinoid receptor inverse agonist also called Rimonabant) analog, 1-(2,4-Difluorophenyl)-4-methyl-N-(1-piperidinyl)-5-[4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, ENP11, that so far, as we have previously shown, has induced changes in glucose availability, i.e. hypoglycemia, in rats. In this study we tested the effects, if any, of ENP11 (0.5, 1.0, and 3.0mg/kg) in food ingestion, core temperature, pain perception and motor control in adult Wistar rats. Results showed that ENP11 reduced food ingestion during the first hour immediately after administration. Likewise, ENP11 (1.0mg/kg) blocked anandamide (AEA)-induced hyperphagia during the first 4h of the dark phase of the light-dark cycle, and it also blocked AEA-induced hypothermia. However, none of the ENP11 doses used affected pain perception or motor control. We believe that ENP11 is a potential useful CB1R antagonist that reduces food ingestion and regulates core temperature.
authors.affiliation: Grupo de Neurociencias de la UNAM, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Méndez-Díaz
authors.affiliation: Grupo de Neurociencias de la UNAM, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico.
authors.forename: Octavio
authors.initials: O
authors.lastname: Amancio-Belmont
authors.affiliation: Grupo de Neurociencias de la UNAM, Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hernández-Vázquez
authors.affiliation: Grupo de Neurociencias de la UNAM, Laboratorio de Neurogenómica Cognitiva, Coordinación de Psicofisiología, Facultad de Psicología, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico.
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: Ruiz-Contreras
authors.affiliation: Grupo de Neurociencias de la UNAM, Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
authors.affiliation: Grupo de Neurociencias de la UNAM, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. 04510 Mexico. Electronic address: opg@unam.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Prospéro-García
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D063388:Endocannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D006963:Hyperphagia / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D008297:Male; D010146:Pain / Q000523:psychology; D058748:Pain Perception / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*
chemical_list: C000606481:1-(2,4-difluorophenyl)-4-methyl-N-(1-piperidinyl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxamide; D001067:Appetite Depressants; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C078814:anandamide
keywords: CB1R; Core temperature; ENP11; Endocannabinoids; Food ingestion