A humanized anti‐cocaine monoclonal antibody antagonizes cocaethylene entry into the brain in mice

Abstract

A humanized anti‐cocaine monoclonal antibody (mAb), h2E2, has been reported to sequester cocaine in the plasma and decrease cocaine concentrations in the brain in mice and to antagonize cocaine‐induced reinstatement of self‐administration behavior in rats. This predicts that h2E2 will decrease the probability of relapse in cocaine abusers. Many cocaine users also abuse alcohol and when cocaine and ethanol are simultaneously ingested, the active metabolite cocaethylene is formed. This potentially compromises the efficacy of h2E2. However, the mAb h2E2 has high affinity for cocaethyene as well as cocaine. In the present study, the ability of h2E2 to prevent cocaethylene entry into the brain was tested. Mice were infused with h2E2 (1.6 μmol/kg i.v.) or vehicle and after one hour were injected with cocaethylene fumurate at a dose equimolar with the mAb. After 5 min, plasma and brain were collected and cocaethylene concentrations were measured by gas chromatography/mass spectrometry with reference to internal and external standards. The h2E2 produced a >; 90% increase in plasma cocaethylene concentrations and a concomitant >; 90% decrease in brain concentrations. The ability of h2E2 to protect the brain from both cocaine and cocaethylene predicts that the clinical efficacy of h2E2 will be retained in cocaine abusers who also co‐abuse alcohol. Supported by NIH grant DPIDA031386 and 2012 ASPET SURF Program.