Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and airway hyperreactivity

Abstract

Salbutamol consists of a racemic mixture of R-and S-salbutamol. R-salbutamol (levalbuterol) is the active bronchodilating enantiomer, whereas S-salbutamol is thought to be pharmacologically inactive or to exert adverse effects.This study evaluated the bronchoprotective effects of inhalation of therapeutically relevant doses of the racemate and individual enantiomers in guinea pigs.It was found that basal airway reactivity to histamine was similarly reduced 30 min after inhalation of equivalent doses of RS-and R-salbutamol; this protective effect disappeared within 3 h. Inhalation of RS-and R-salbutamol 30 min before and 5.5 h after allergen challenge suppressed allergen-induced airway hyperreactivity to histamine after the early and late asthmatic reaction, completely inhibiting the early asthmatic reaction and tending to reduce the development of the late asthmatic reaction. At 5 h after allergen challenge, the inhibition of airway hyperreactivity was more pronounced in animals treated with R-salbutamol compared to racemate-treated animals. Both basal airway reactivity and allergen-induced hyperreactivity were not affected by S-salbutamol. Inflammatory cell infiltration was not affected by the racemate or the individual enantiomers.In conclusion, inhalation of therapeutically relevant doses of R-and RS-salbutamol effectively suppress allergen-induced airway reactivity after the early and late asthmatic reactions, the Renantiomer being slightly more potent with respect to early airway reactivity than the racemate. No adverse effects were observed for the S-enantiomer.

Bronchoprotection by Olodaterol Is Synergistically Enhanced by Tiotropium in a Guinea Pig Model of Allergic Asthma

“…However, cell infiltration in the BAL after the LAR was not affected. These findings correspond well with previous findings with salbutamol inhalations in our model (Westerhof et al, 2005), although, as might be expected, the effects of the long-acting olodaterol on the allergen-induced asthmatic reactions and AHR in the present study were more pronounced.…”

“…In a similar setup, we previously demonstrated that a clinically relevant dose of 2.5 mM salbutamol (nebulizer concentration, 3 minutes) also reversed allergeninduced AHR to histamine in guinea pigs, though with a smaller effect (∼3-fold increase in PC 100 ) (Westerhof et al, 2005).…”

Enantiomer-Specific Effects of Albuterol on Airway Inflammation in Healthy and Asthmatic Cats

“…Differential effects of the single isomer forms of albuterol in animal models of asthma were evaluated previously by only two groups of investigators [8, 23]. The first study, using a murine model of asthma, concluded that both isomers reduced airway eosinophil trafficking, but that only the S -enantiomer increased airway hyperresponsiveness [8].…”

“…In the second study, guinea pigs were sensitized to OVA and administered 3 doses of racemic or single isomers of albuterol by inhalation [23]. Animals showed no differences in the numbers or types of inflammatory cells in the BALF between treatment and placebo groups [23]. The major limitations to that study were the use of OVA as an allergen, the method of aerosol delivery not accurately modeling the route of delivery in humans (i.e.…”

“…However, three major issues limit the ability to extrapolate the results of that study to humans with asthma: (1) the murine model used ovalbumin (OVA) to sensitize and challenge mice, and OVA is not a clinically relevant allergen in humans; (2) R - and S -enantiomers were administered systemically by insertion of a subcutaneous pump, and not by inhalation, and (3) the investigators failed to use racemic albuterol as a control, which is important since other in vitro studies have shown proinflammatory effects or alterations in mucociliary clearance only when the two isomers are administered simultaneously [4, 24]. In the second study, guinea pigs were sensitized to OVA and administered 3 doses of racemic or single isomers of albuterol by inhalation [23]. Animals showed no differences in the numbers or types of inflammatory cells in the BALF between treatment and placebo groups [23].…”