Tunek_1988_Drug.Metab.Dispos_16_759

Bambuterol, the bis-dimethyl carbamate prodrug of terbutaline, was tested for its potency in inhibiting cholinesterases in human blood. Preincubation of blood with bambuterol in the absence of thiocholine ester substrate was essential for obtaining maximal inhibition. The inhibition exerted by bambuterol after such preincubation was reversible and noncompetitive. Bambuterol was an extremely effective inhibitor of cholinesterase when butyrylthiocholine was used as substrate (I50 = 1.7 +/- 0.3 x 10(-8) M, N = 10) whereas it was 2400-fold less efficient in inhibiting cholinesterase with acetylthiocholine as substrate (I50 = 4.1 +/- 0.5 x 10(-5) M, N = 10). Because butyrylthiocholine is the preferred substrate for cholinesterase (EC 3.1.1.8) and acetylthiocholine for acetylcholinesterase (EC 3.1.1.7), these results indicate that bambuterol is a remarkably selective and potent inhibitor of cholinesterase.