V4N2: An Anticocaine Immunogen

The present study reports the design, synthesis & preclinical evaluation of a novel calix[n]arene-based anti-cocaine immunogen (herein named as V4N2) by the tethering of the hydrolysis-tolerant hapten GNE onto the calix[4]arene moiety. The preclinical assessment corresponded to the immunogenicity and dose-response evaluation of V4N2. The potential of the produced antibodies to reduce the passage of cocaine analogue through the blood-brain-barrier (BBB), modifying it's biodistribution was also investigated. The calix[n]arene-based immunogen elicited high titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue 99m Tc[TRODAT-1] and decreased cocaine-induced behaviour, according to an animal model. The present results demonstrate the potential of V4N2 as an immunogen for the treatment of cocaine use disorder.