摘要：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 β2 adrenergic agonist in guinea pigs and rabbits, in comparison with other β2 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 (pD2, pA2 or ED50) 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 pD2 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 β2 adrenoceptor because this effect was easily antagonized by ICI-118551 (pA2 8.90±0.01), a specific β2 adrenoceptor antagonist. SPFF also dose-dependently relaxed the isolated guinea pig trachea strip precontraction with acetylcholine or histamine with ED50 values of 10.2±0.7 μ M and 550±38.2 n M , respectively. Furthermore, the positive chronotropic effect of SPFF on isolated guinea pig left atria (pD2 5.41±0.38) was much weaker than that of isoprenaline (pD2 8.75±0.24), which implied that SPFF was more selective to airway β2 adrenoceptor than isoprenaline; the β1/β2 selectivity assay also showed that SPFF was about 162 times more selective to β2 adrenoceptor than isoprenaline. A radioligand binding experiment using guinea pig lung and cardiac ventricle as β2 and β1 adrenoceptor sources, respectively, also demonstrated that SPFF possesses high affinity (27.3 n M ) and selectivity (4.6 fold) to β2 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 ED50 value of SPFF i.g. was 0.32±0.05 mg·kg−1 in this experiment. Meanwhile, the ED50 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 β2 adrenoceptor selectivity.
