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Bronchoprotective effect of zardaverine versus theophylline in rats

Bronchoprotektiver Effekt von Zardaverin gegen Theophyllin in Ratten
: Hoymann, H.G.; Beume, R.; Kilian, U.; Heinrich, U.

Naunyn-Schmiedebergs archives of pharmacology 344 (1991), S.R75
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Pharmakologie und Toxikologie <1991, Berlin>
Fraunhofer ITA ( ITEM) ()
Asthma; bronchial provocation test; bronchialer Provokationstest; Lungenfunktionstest; phosphodiesterase inhibitor; Phosphodiesteraseinhibitor; rat; Ratte; respiratory function test; Theophyllin; theophylline; Zardaverin; zardaverine

Zardaverine is a new selective PDE III/IV inhibitor with potent bronchospasmolytic activity in guinea pigs. We recently compared the bronchodilating and bronchoprotective potency of zardaverine and the nonselective PDE inhibitor theophylline by measuring typical spontaneous and forced respiratory funcfion parameters in anaesthetized rats using whole-body plethysmography. 60 female Wistar rats (240 g) were used in the experiment. Zardaverine (3, 10, 30 mymol/kg) and theophylline (30, 100, 300 umol/kg), respectively, were given orally in 4 % Methocel/0.9 % saline solution after more than 15 h starving. 20 min after treatment the measurements were started. One week earlier, to obtain control values, measurements were performed 20 min after feeding the vehicle. When spontaneously breathing, the 30 Amol/kg zardaverine (300 mymol/kg theophylline) treated animals showed a 23 % (14 %, ns) decreased lung resistance and a 43 % (25 %) elevated dynamic compliance. There was no indication of a chan ged lung elasticity based on quasistatic compliance and therefore the increased dynamic compliance as well as the decreased resistance can only be caused by bronchodilation. In the acetylcholine challenge test treatment with only 10 umol/kg zardaverine (but 300 mymol/kg theophylline) revealed a 37 % (28 %) lower resistance and 85 % (44 %) higher compliance. This indicates a better bronchoprotective effect of zardaverine which was also supported by Peak Flow, FEF50 and FEF25 measurement after challenge.