Mechanism of the antitussive effect of azelastine in guinea pigs.
In order to clarify the mechanism of the antitussive effects of azelastine hydrochloride (azelastine, CAS 790307-93-0), the cough responses to inhaled capsaicin and substance P (SP) were evaluated before and after the administration of azelastine in conscious guinea pigs. The concentrations of SP were also measured before and after the administration of azelastine by radioimmunoassay in anesthetized guinea pigs. Capsaicin and SP caused coughing in conscious guinea pigs in a dose-dependent fashion. After the treatment with azelastine, capsaicin-induced cough decreased significantly, and the dose-response curve to capsaicin was shifted to a higher concentration in comparison with the the controls. SP-induced cough was not inhibited by the treatment with azelastine, and the dose-response curves to SP did not change. The concentrations of SP recovered in bronchoalveolar lavage fluid and in the trachea were decreased statistically significantly in a dose-dependent manner after the treatment with azelastine, while the SP concentrations of the subjects not treated with azelastine were not inhibited. These results suggest that the antitussive effect of azelastine might be partly due to the inhibition of SP release from sensory nerves in guinea pigs.
Second Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
Nobuaki
N
Ito
Takanobu
T
Shioya
Akiko
A
Watanabe
Masaaki
M
Sano
Masahiro
M
Sasaki
Mamoru
M
Miura
D000818:Animals; D000996:Antitussive Agents; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006168:Guinea Pigs; D010793:Phthalazines / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000996:Antitussive Agents; D010793:Phthalazines; D013373:Substance P; D002211:Capsaicin; C020976:azelastine