Connors_2013_J.Pharmacol.Exp.Ther_347_251

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. Although there is no true antidote to cocaine toxicity, current management strategies address the life-threatening systemic effects, namely hyperthermia, vasospasm, and severe hypertension. Clinicians rely on rapid cooling, benzodiazepines, and alpha-adrenergic antagonists for management, with years of proven benefit. Experimental agents have been developed to more effectively treat acute toxicity. Pharmacodynamic approaches include antipsychotics that are thought to interfere with cocaine's actions at several neurotransmitter receptors. However, these medications may worsen the consequences of cocaine toxicity as they can interfere with heat dissipation, cause arrhythmias, and lower the seizure threshold. Pharmacokinetic approaches use cocaine-metabolizing enzymes, such as butyrylcholinesterase (BChE), cocaine hydrolase (CocH), and bacterial cocaine esterase (CocE). Experimental models with these therapies improve survival, primarily when administered before cocaine, although newer evidence demonstrates beneficial effects shortly after cocaine toxicity has manifested. CocE, a foreign protein, can induce an immune response with antibody formation. When enzyme administration was combined with vaccination against the cocaine molecule, improvement in cocaine-induced locomotor activity was observed. Finally, lipid emulsion rescue has been described in human case reports as an effective treatment in patients with hemodynamic compromise because of cocaine, which correlates well with its documented benefit in toxicity due to other local anesthetics. A pharmaceutical developed from these concepts will need to be expedient in onset and effective with minimal adverse effects while at the same time being economical.