Cheating Cocaine with Chelation.
Abstract Number: 92
Abstract Type: Original Research
Introduction: The anesthetic management of the cocaine toxic parturient can be challenging. Cocaine blocks the pre-synaptic uptake of norepinephrine leading to tachycardia, hypertension, myocardial ischemia, placental abruption, and preterm labor. Tocolytics are limited to magnesium. The use of beta blockers can lead to unopposed alpha-receptor stimulation. Decades of research to create a cocaine receptor antagonist have proved futile. Chelating cocaine with a macrocycle is a possible alternative.
Methods: We purchased a set of cyclodextrins, cucurbiturils and sulfocalixarenes from Sigma Aldrich. A series of isothermal calorimetric titrations were performed to determine the affinity of these macrocycles to cocaine.
Results : Cucurbiturils and cyclodextrins show no affinity for cocaine. Increasing the size of the macrocycle ring of sulfocalixarenes from four to six doubles the affinity constant from 6570 to 12,600M-1.
Discussion: Macrocycles can bind cocaine on the order of 10^4, sugammadex can bind rocuronium with an affinity of 10^7. By modifying the sulfocalixarene it will be possible to improve affinity. Chelation is a more practical therapeutic approach than creating a catalytic antibody or finding a mutant butyrylcholinesterase to accelerate cocaine metabolism.
Ref: Zheng, Org. Biomol.Chem.,2088,6,836-843