The Impact Of Bambuterol And Terbutaline’s Enantiomers On Guinea Pig’s Pulmonary Function

Bambuterol is a long acting beta-agonist(LABA). While itself has no function of activing beta2 receptor. It can be turned to terbutaline in body by butyrylcholinesterase then active beta 2 receptor. Bambuterol is chiral and also have two enantiomers R-form and S-form. Beta-agonists is in common use as anti-asthmatic medicine in clinical. While its’ two main side effect are drug-related airway anomalies(hyper-responsiveness) and tolerance which have influence on its’ clinical use. Beta-agonists in market are mainly racemic and have the same amout of R-enantiomer and S-enantiomer. In this project we have studied S-enantiomer’s potation role in inducing airway anomalies and tolerance. Found that exclusive use of S-enantiomer would induce the airway hyper-responsiveness in guinea pig. At the same time sustained use of S-enantiomer have no efficacy of anti-astmatic but can induce guinea pig get a tolerance to R-enantiomer. Following is the main content of this study:(1) We have successfully constructed a pulmonary function evaluation system for faunle.Compare with Buxco system our system is cheaper and more accurate.(2) Compared with diffirent asthmatic-induced agents and method, we finally chose histaminewhich has a strong function of asthmatic-induced and have lest individual difference toobserve above-mentioned agents’ efficacy.(3) Bambuterol study: sustained ingastric lavarge of racemic and S- enantiomer of bambuterol14 day(4mg/kg*day) in guinea pig, then test its’ response to histamine(i.v.). The resultshowed that, compared with saline group guinea pig’s response to histamine is notablelyhigher in S-bambuterol group. The increased rate of pulmonary ressistance are156.68%±98.7% and 37.43%±24.1%, P<0.05, respectively. And the decreased rate of lungdynamic complance are 46.82%±6.76% and 22.3%±6.28%,P<0.001. Indicated thatS-bambuterol has relationship with hyper-responsiveness. After sustained ingastric lavargeof S- bambuterol 14 day(4mg/kg*day) in guinea pig. We observed R-bambuterol’sefficacy(4mg/kg) in inhibiting histamine induced asthmatic, found that compared withsaline group the efficacy of R-bambuterol is notablely lower in S-bambuterol group. Theincreased rate of pulmonary ressistance are 132.25%±26.58% and16.72%±6.49%,P<0.01,respectively. Indicated that S-bambuterol has relationship withracimic bambuterol’s side effect of tolerance. At the same time, we have found thatabove-mentioned tolerance has a big incividual difference in guinea pig.(4) Terbutaline study: consecutively inhaling different enantiomers(4mg/ml, 2min*5 times) of terbutaline in guinea pig observe R-terbutaline’s efficacy(1mg/ml, 1min) in inhibiting histamine induced asthmatic, found that compared with saline group the efficacy of R-terbutaline is notablely lower in S- terbutaline group. The △R are 13.35%±9.67% and 96.47%±3.29%, P<0.05, respectively. The △C are 12.69%±4.34% and 68.3%±15.74% P<0.05, respectively.Indicated that S-terbutaline has relationship with racimic terbutaline’s side effect of tolerance.