THERAPEUTIC USE OF BUTYRYLCHOLINESTERASE FOR COCAINE INTOXICATION

The most common complications of cocaine ingestion are on the cardiova scular and central nervous systems and produce chest pain and generali zed seizures, In humans, decreased levels of butyrylcholinesterase (BC hE) (EC 3.1.1.8) have been associated with sustained effects of cocain e and life-threatening complications. Administration of purified human BChE has previously been demonstrated to protect against cocaine-asso ciated cardiovascular toxicity in rats. A shift in the metabolism of c ocaine as well as enhanced metabolism may be the underlying mechanism of the enzyme. Therefore, levels of the parent drug and four metabolit es were determined in rat plasma after ip administration of a lethal c ocaine dose, followed by iv administration of BChE, Plasma and brain c oncentrations of cocaine were lowered by 80% after BChE administration , Furthermore, the metabolic profile of cocaine in the plasma was alte red, The concentration of ecgonine methylester was doubled although th e concentration of ecgonine, a secondary metabolite of cocaine, was re duced. The level of bennoylecgonine was reduced by one-half while norc ocaine was absent. Cocaine-associated effects upon the central nervous system were also shown to be reduced by administration of BChE to con scious rats, Furthermore, our studies in the cat have also shown that purified BChE shifts the metabolic profile of cocaine (1 mg/kg) to the pharmacologically inactive products ecgonine methylester and ecgonine . Pretreatment with BChE (0.27, 1.0, and 10.0 mg/kg) ameliorated the h ypertensive effects of cocaine (1 mg/kg) by reducing the duration and the extent of BP elevation by 66%, Administration of the enzyme, 1 min after cessation of cocaine infusion, resulted in an immediate attenua tion in the cocaine-induced broadening of the QRS complex. These resul ts suggest that BChE could be an effective and rapid therapy for the t reatment of life-threatening cocaine-induced cardiovascular effects in human while clearing the total body burden of cocaine. (C) 1997 Acade mic Press.