Stereoselective inhibition of human, mouse, and horse cholinesterases by bambuterol enantiomers

Stereoselective inhibition of butyrylcholinesterase by enantiomers ofexo- andendo-2-norbornyl-N-n-butylcarbamates

“…K i and k i values for the racemic inhibitor are about the average of those of both enantiomers (Table 2). However, this stereopreference (S < R) is opposite to those reported for the BChE-catalyzed hydrolysis enantiomers of quinuclidin-3-acetate 50 , bambuterol 51 , quinuclidinium benzoate 52 , and cocaine 53 . Modeling both enantiomers of endo-2-norbornyl-N-n-butylcarbamate into the active site of the X-ray structure of BChE 4,5 ( Figure 1) suggests that the norbornyl ring of (S)-enantiomer fits better into the AS of the enzyme than (R)-enantiomer ( Figure 5B).…”

“…This stereopreference (R < S) is the same as those reported for the BChE-catalyzed hydrolysis enantiomers of (Table 2). quinuclidin-3-acetate 50 , bambuterol 51 , quinuclidinium benzoate 52 , and cocaine 53 . Modeling both enantiomers of exo-2-norbornyl-N-n-butylcarbamate into the active site of BChE 4,5 ( Figure 1) indicates that the norbornyl ring of (R)-enantiomer fits better into the AS of the enzyme than that of (S)-enantiomer ( Figure 5A).…”

Cholinesterases: Structure, Role, and Inhibition

“…AChE je tako stereoselektivna prema karbamatima (-)-fizostigminu, (-)-fizoveninu, (-)-kimserinu i (R)-bambuterolu, dok su AChE i BChE pokazale veći afi nitet prema (R)-etopropazinu, lijeku koji se, u obliku racemata, rabi kao neuroleptički lijek u tretmanu Parkinsonove bolesti (93)(94)(95)(96)(97). Karboksilni esteri, esteri karbaminske kiseline i trifl uoracetofenoni planarne su molekule kod kojih su skupine vezane direktno na elektrofi lni ugljik pod kutovima od 120º čineći tako trigonalnu geometriju.…”

Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs

“…Recent studies have indicated that S-enantiomer of b2-adrenoceptor agonists is a less active or inactive bronchodilatorily, while S-terbutaline may cause adverse effects contributing to morbidity and even mortality in asthma patients (Handley et al 1998;Waldeck 2002). Additionally, R-bambuterol displayed two-fold higher potency than racemic bambuterol (rac-bambuterol) in the treatment of asthma in guinea pigs and five-fold higher potency for in vitro inhibition of BuChE than S-bambuterol in human, mouse, and horse BuChE (Bosak et al 2008). Given this possibility, the question of whether b2-agonists should be administered as pure active R-enantiomer (the ''racemic switch'') is currently under consideration.…”