In this paper we evaluated the
bronchodilator effects of SPFF [2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-
ethanol chloride], a newly synthesized beta(2)
adrenergic agonist in guinea pigs and rabbits, in comparison with other beta(2)
adrenergic agonists,
isoprenaline or
salbutamol. We studied in vitro the
bronchodilator effects of SPFF and
isoprenaline on isolated guinea pig trachea strips with or without the precontraction of bronchocontractors (
acetylcholine and histamie). The positive chronotropic effects of SPFF and
isoprenaline on isolated guinea pig left atria were also tested in vitro. Potency values (pD(2), pA(2) or ED(50)) were determined from the cumulative concentration-response curves. The results showed that SPFF and
isoprenaline dose-dependently relaxed the isolated guinea pig trachea strips and the pD(2) values of both drugs were 7.66+/-0.68 and 8.79+/-0.19, respectively. Moreover, we confirmed that the
bronchodilator effect of SPFF was due to the activation of beta(2)
adrenoceptor because this effect was easily antagonized by
ICI-118551 (pA(2) 8.90+/-0.01), a specific beta(2)
adrenoceptor antagonist. SPFF also dose-dependently relaxed the isolated guinea pig trachea strip precontraction with
acetylcholine or
histamine with ED(50) values of 10.2+/-0.7 microM and 550+/-38.2 nM, respectively. Furthermore, the positive chronotropic effect of SPFF on isolated guinea pig left atria (pD(2) 5.41+/-0.38) was much weaker than that of
isoprenaline (pD(2) 8.75+/-0.24), which implied that SPFF was more selective to airway beta(2)
adrenoceptor than
isoprenaline; the beta(1)/beta(2) selectivity assay also showed that SPFF was about 162 times more selective to beta(2)
adrenoceptor than
isoprenaline. A radioligand binding experiment using guinea pig lung and cardiac ventricle as beta(2) and beta(1)
adrenoceptor sources, respectively, also demonstrated that SPFF possesses high affinity (27.3 nM) and selectivity (4.6 fold) to beta(2)
adrenoceptors. The protective effects of SPFF and
salbutamol on
bronchospasm induced by bronchoconstrictor
aerosol in guinea pigs in vivo were investigated, and the Konzett and Rössler experiment in rabbits in vivo was also carried out. SPFF significantly prolonged the latency time of
histamine and
acetylcholine induced asphyxiation collapse in guinea pigs: the ED(50) value of SPFF i.g. was 0.32+/-0.05 mg.kg(-1) in this experiment. Meanwhile, the ED(50) values of
salbutamol was 2.37+/-0.22, which meant that the bronchorelaxation effect of
salbutamol was about 6 times less potent than that of SPFF. The Konzett and Rössler experiment performed in anesthetized rabbit showed that intraduodenal administration of SPFF exerted action of longer duration than
salbutamol. From the results above we suggested that SPFF was a potent, long-acting
bronchodilator with relatively higher beta(2)
adrenoceptor selectivity.