M. Pairet et al., AMBROXOL IMPROVES THE BRONCHO-SPASMOLYTIC ACTIVITY OF CLENBUTEROL IN THE GUINEA-PIG, Journal of Pharmacy and Pharmacology, 49(2), 1997, pp. 184-186
The effects of ambroxol on the spasmolytic action of clenbuterol were
investigated on acetylcholine-induced bronchospasm in guinea-pigs. Amb
roxol (50 mg kg(-1) day(-1)) or vehicle was administered orally for 14
days. Approximately 45 min after the final dose on day 14, the animal
s were anaesthetized and the spasmolytic effects of clenbuterol (3, 6
or 12 mu g kg(-1) injected intravenously) were determined by use of ac
etylcholine (40 mu g kg(-1) i.v.)-induced bronchoconstriction. For bot
h vehicle- and ambroxol-treated animals, a positive linear relationshi
p was observed between the log-dose of clenbuterol and the percent inh
ibition of bronchospasm. The calculated ED25 of clenbuterol (i.e. the
dose producing 25% inhibition of the acetylcholine-induced bronchospas
m) was 3.98 mu g kg(-1) (3.29 to 4.82 mu g kg(-1), 95% confidence inte
rval) in the presence of ambroxol and 5.81 mu g kg(-1) (4.98 to 6.79 m
u g kg(-1)) in the absence of ambroxol. The linear regressions with or
without ambroxol differed from each other (P < 0.001) but ran paralle
l (covariance analysis), enabling us to calculate a relative potency,
the value of which was 1.46 (1.16 to 1.84). These results demonstrate
that the spasmolytic activity of clenbuterol is significantly improved
in animals pretreated with ambroxol.