摘要：Previous study on racemic SPFF [2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2- tert -butylamino-ethanol hydrochloride], a novel β2-adrenoceptor agonist, has validated that it is a potent, long-acting bronchodilator with relative higher β2-adrenoceptor selectivity. On the basis of this study, we compared the pharmacological properties of SPFF and its enantiomers ((−)-SPFF and (+)-SPFF) in guinea pigs taking isoprenaline or salbutamol (SAB) as referenced drugs. For the relaxation of both normal and precontracted trachea strips in vitro , (−)-SPFF was found more potent than (±)-SPFF or (+)-SPFF. Moreover, we confirmed that the bronchodilator effect of (−)- and (+)-enantiomers were due to activation of the β2-adrenoceptor because this effect was antagonized by a specific β2-adrenoceptor antagonist, ICI-118551, with similar pA2 values to those of (±)-SPFF. Radioligand binding assay revealed that affinity of (−)-enantiomer to β2-adrenoceptor was 6 and 164 fold greater than that of (±)- and (+)-SPFF, respectively. In addition, isomeric difference of overall selectivity between (−)-SPFF and (+)-SPFF was 10.7 fold for lung versus atria. (−)-SPFF displayed almost the same protective effect against bronchospasm induced by histamine-acetylcholine aerosol in conscious guinea pigs as (±)-SPFF did. However, the latent time of (+)-SPFF (1 mg·kg−1) was significantly shorter than that of (±)- and (−)-SPFF at the same doses. Finally, in the inhibition of histamine-induced increase of pulmonary resistance ( R L) in anesthetized guinea pigs, (−)-SPFF was 1.3 and 3.5 times more potent than (±)- and (+)-SPFF. Correspondingly, in inhibiting the decrease of pulmonary compliance ( C L) , the potencies of (−)- and (+)-enantiomers were approximately equivalent to that of (±)-SPFF. Furthermore, a study on the long-lasting action of the test drugs had shown that the effects of (−)-SPFF (30 μg·kg−1), (±)-SPFF (30 μg·kg−1) and (+)-SPFF (100 μg·kg−1) in inhibiting the increase of R L all lasted for 4 h. Nevertheless, the effects of (−)- and (+)-enantiomers were slightly lower 4 h after intraduodenal administration in inhibiting the decrease of C L. In conclusion, (−)-SPFF may be beneficial for the treatment of asthma because of its more potent efficacy and higher adrenoceptor affinity than (±)- or (+)-SPFF.
