The effects of a humanized anti‐cocaine monoclonal antibody on the cardiovascular effects of cocaine in mice (848.2)

Abstract

A humanized anti‐cocaine monoclonal antibody, h2E2, in mice increased plasma cocaine concentrations 10‐20‐fold with a concomitant decrease in brain concentrations. This antagonized cocaine‐induced reinstatement of self‐administration behavior but the cocaine buildup in the peripheral circulation may cause adverse effects on cardiovascular function. To examine this, mice were pre‐treated 24 hours prior to cocaine administration with h2E2 (120 ug/g iv) or vehicle control. h2E2 alone had only mild effects on cardiac and vascular function. Left ventricular (LV) performance and carotid blood flow were measured during cumulative dosing with cocaine (1, 3, 10 and 30 ug/g; 5 min intervals). In vehicle‐treated mice (Veh), cocaine increased LV dP/dt and this effect was not altered by the presence h2E2 (34% vs. 36% increase Veh vs. h2E2, at the highest dose). Measurements of blood pressure revealed similar changes. h2E2 modestly increased cerebral vascular resistance at baseline (60 ± 7 vs. 82 ± 12 ml/min/mmHg in Veh vs. h2E2, respectively), but had no effect on the constrictor effects of cocaine (21% vs 26% increase in Veh vs. h2E2). These data show that there were no adverse cardiovascular effects of h2E2 in mice, and its sequestering cocaine in the vascular space did not increase the cardiotonic or vasoactive effects of cocaine. We conclude that cocaine bound to the antibody within the circulation is not bioactive.Grant Funding Source: Supported by NIH grant DP1DA031386