| SPFF, [2-(4-Amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol chloride], was a new synthesizedβ2 adrenergic agonist. (±)-SPFF, as a racemic mixture, could relax the trachea smooth muscle, stabilize lung mast ceils and improve the cilium transportation, therefore eventually alleviate the asthmatic symptom.The research of (-)-SPFF demonstrated the action of relaxing trachea smooth muscle and alleviating asthmatic symptom through the experiments on intact animals and isolated organs, compared with (+)-SPFF.We studied the bronchodilation effects of (-)-SPFF, (+)-SPFF and ISO (isoprenaline) on isolated guinea pig trachea strips with or without the pre-contraction of bronchocontractors (His and Ach). (-)-SPFF and (+)-SPFF dose-dependently decreased the resting tension of isolated guinea pig trachea strips with the pD2 value of 7.77±0.09 and 6.73±0.40, respectively. (-)-SPFF and (+)-SPFF also dose-dependently relaxed the isolated guinea pig trachea strips pre-contracted with His or Ach. The maximum relaxation rate of (-)-SPFF and (+)-SPFF pre-contracted with His were 123.51％and 126.47％, respectively. The potency of (+)-SPFF was less than that of (-)-SPFF about 3.70 times. The maximum relaxation rate of (-)-SPFF and (+)-SPFF pre-contracted with Ach were 81.77％and 70.54％, respectively. The potency of (+)-SPFF was less than that of (-)-SPFF about 27.86 times. Moreover, we confirmed that the bronchodilation effects of (-)-SPFF and (+)-SPFF were due to the activation ofβ2 adrenoceptor because the effects were easily antagonized by ICI-118551 (pA2 8.94±0.01 & 8.89±0.05), a specificβ2 adrenoceptor antagonist. In addition, (-)-SPFF and (+)-SPFF (2×10-3 -2×10-7mol/L) significantly inhibited the bronchoconstriction effect of histamine in isolated lung perfusion model of guinea pigs. But the effect of (-)-SPFF was about 30.24 times more potent than that of (+)-SPFF.The protective effects of (-)-SPFF and (+)-SPFF on bronchospasm induced by bronchoconstrictor aerosol in guinea pigs in vivo were investigated, and the Konzett and R(?)ssler experiment in guinea pigs in vivo was also performed. The results showed that (-)-SPFF significantly prolonged the latency time of the asphyxiation collapse induced by histamine and acetylcholine in guinea pigs: the ED50 value of (-)-SPFF i.g. was 2.02±0.61mg/kg. In this experiment, the protective effect of (-)-SPFF was 15.02 times as that of (+)-SPFF. The result of the Konzett and Rossler experiment performed in anesthetized guinea pigs showed that the effect of (-)-SPFF had marked difference compared with SAB(100μg/kg) at 30min after intraduodenal administration, and (+)-SPFF didn't exert an action at 30min. The ED50 value of (-)-SPFF was 4.09±0.89μg/kg, and the protective effect was 7.92 times as that of (+)-SPFF at 60min. The result also showed that (-)-SPFF and (+)-SPFF exerted an action of longer duration than salbutamol after intraduodenal administration. (-)-SPFF and (+)-SPFF also significantly improved the alteration of lung resistance and compliance induced by His in anesthetized guinea pigs at 30min. Improving the increase of lung resistance, the ED50 value of (-)-SPFF was 4.74±0.91μg/kg, and the protective effect was 3.51 times as that of (+)-SPFF. From the results above, we suggested that (-)-SPFF was a potent, long-acting bronchodilator. Moreover, (-)-SPFF and (+)-SPFF (3×10-8 -3×10-6mol/L) inhibited the release of histamine in ovalbumin-allergic rats lung fragments, which indicated a mast cell protection effect. In the investigation of the effect of (-)-SPFF on the mucus movement, it was shown that (-)-SPFF (0.04, 0.10mg/kg) improved the cilium transportation function on the trachea of conscious pigeon compared with (+)-SPFF, while it had no effect on the airway mucus excretion in mice. These results implied that, by prompting the clearance of airway, (-)-SPFF had an additional beneficial effect on the alleviation of asthma symptom.In conclusion, (-)-SPFF and (+)-SPFF, both wereβ2AR agonists and stabilizers of lung mast cells by the activation ofβ2AR. Compared with (+)-SPFF, (-)-SPFF induced more potent relaxation of the trachea smooth muscle, and improved the cilium transportation function, therefore eventually resulted in the alleviation of the asthmatic symptom. The results indicated that (-)-SPFF was superior to (+)-SPFF.
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