Cristina Fernández-Fernández 1 , Luis F Callado 2 , Rocío Girón 3 , Eva Sánchez 3 , Amaia M Erdozain 2 , José Antonio López-Moreno 4 , Paula Morales 1 , Fernando Rodríguez de Fonseca 5 , Javier Fernández-Ruiz 6 , Pilar Goya 1 , J Javier Meana 2 , M Isabel Martín 3 , Nadine Jagerovic 1
20 February 2014
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 CB 1 and CB 2 cannabinoid and μ opioid receptors. In [ 35S]-GTPγS (guanosine 5′-O-[gamma-thio]triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB 1 cannabinoid antagonists and μ opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.