Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases.

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Gazic I, Bosak A, Sinko G, Vinkovic V, Kovarik Z

Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases.

Anal Bioanal Chem. 2006 Aug;385(8):1513-9. Epub 2006 Jul 25.

PubMed ID

16865342 [ View in PubMed

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Abstract

We separated and characterized the enantiomers of bambuterol (5-[-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride), which is used in racemic form as a prodrug of terbutaline, a beta(2)-adrenoceptor agonist. The enantioseparation was attempted on several chiral HPLC columns, and the most effective separation was achieved on the amylose-based Chiralpak AD column. Since in vivo conversion of bambuterol into terbutaline involves hydrolysis by butyrylcholinesterase (EC 3.1.1.8), we studied the reaction of enantiomers with eight human BChE variants. Both enantiomers inhibited all studied BChE variants; however, the rate of inhibition with the (R)-enantiomer was about five times faster than with the (S)-enantiomer. (R)-bambuterol inhibition rate constants for homozygous usual (UU), fluoride-resistant (FF) or atypical (AA) variant ranged from 6.4 to 0.11 min(-1)microM(-1). The inhibition rates for heterozygotes were between the respective constants for the corresponding homozygotes.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Bambuterol	Cholinesterase	Protein	Humans	Unknown	Substrate Inhibitor	Details