Ambroxol improves the broncho-spasmolytic activity of clenbuterol in the guinea-pig.
The effects of ambroxol on the spasmolytic action of clenbuterol were investigated on acetylcholine-induced bronchospasm in guinea-pigs. Ambroxol (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 animals were anaesthetized and the spasmolytic effects of clenbuterol (3, 6 or 12 micrograms kg-1 injected intravenously) were determined by use of acetylcholine (40 micrograms kg-1, i.v.)-induced bronchoconstriction. For both vehicle- and ambroxol-treated animals, a positive linear relationship was observed between the log-dose of clenbuterol and the percent inhibition of bronchospasm. The calculated ED25 of clenbuterol (i.e., the dose producing 25% inhibition of the acetylcholine-induced bronchospasm) was 3.98 micrograms kg-1 (3.29 to 4.82 micrograms kg-1, 95% confidence interval) in the presence of ambroxol and 5.81 micrograms kg-1 (4.98 to 6.79 micrograms kg-1) in the absence of ambroxol. The linear regressions with or without ambroxol differed from each other (P < 0.001) but ran parallel (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.
Pairet
M
M
Department of Biological Research, Dr Karl Thomae GmbH, Boehringer Ingelheim Corp., Herbolzheim, Germany.
Engelmann
P
P
Von Nicolai
H
H
Champeroux
P
P
Richard
S
S
Rauber
G
G
Engelhardt
G
G
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D001986:Bronchial Spasm / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002976:Clenbuterol / Q000627:therapeutic use*; D004357:Drug Synergism; D005100:Expectorants / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male
D001993:Bronchodilator Agents; D005100:Expectorants; D000551:Ambroxol; D002976:Clenbuterol