title: Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results.
abstract: Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two wellknown drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and μ opioid receptors. In [(35)S]-GTPγS (guanosine 5'-O-[gamma-thio]triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and μ opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.
authors.affiliation: Instituto de Química Médica, CSIC, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Fernández
authors.affiliation: Departamento de Farmacología, Universidad del Pais Vasco, UPV/EHU, CIBERSAM, Leioa, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.affiliation: Departamento de Farmacología y Nutrición, Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Girón
authors.affiliation: Departamento de Farmacología y Nutrición, Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Sánchez
authors.affiliation: Departamento de Farmacología, Universidad del Pais Vasco, UPV/EHU, CIBERSAM, Leioa, Spain.
authors.forename: Amaia M
authors.initials: AM
authors.lastname: Erdozain
authors.affiliation: Departamento de Psicobiologia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Moreno
authors.affiliation: Instituto de Química Médica, CSIC, Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Morales
authors.affiliation: Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Málaga, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, CIBERNED, IRYCIS, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
authors.affiliation: Instituto de Química Médica, CSIC, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.affiliation: Departamento de Farmacología, Universidad del Pais Vasco, UPV/EHU, CIBERSAM, Leioa, Spain.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.affiliation: Departamento de Farmacología y Nutrición, Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Martín
authors.affiliation: Instituto de Química Médica, CSIC, Madrid, Spain.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jagerovic
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000077285:Rimonabant; D005283:Fentanyl
keywords: behavioral assays; cannabinoid; fentanyl; opioid; rimonabant