Ucelay M, Labeaga L, Orjales A, Zubiaur L, Quintana A
Research Department, FAES S.A., Bilbao, Spain.
Arzneimittelforschung. 1991 May;41(5):528-32.
The bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of 8-(2-phenylethyl)-1-oxa-diazaspiro[4,5]decan-2-one 2-tiophenecarboxylate (decasilate, CAS 76652-72-7) have been evaluated using different experimental models. 1. Decasilate showed a remarkable spasmolytic activity against histamine-induced contractions in the isolated guinea-pig tracheal preparation with an IC50 of 2.7 x 10(-6) mol/l. In addition, the oral administration of decasilate (5-30 mg.kg-1) significantly reduced the histamine aerosol-induced bronchospasm in guinea-pigs. 2. Decasilate had a preventive effect against antigen-induced contractions of ileum segments from sensitized guinea-pigs (EC50 8.0 x 10(-6) mol/l) and relaxed them when added after the antigen challenge (IC50 9.5 x 10(-7) mol/l). 3. Both carrageenin- and dextran-induced rat hind paw oedemas were significantly reduced by the oral administration of decasilate with ED50 values of 169.5 and 34.5 mg.kg-1, respectively. However, it was ineffective against the cotton pellet-induced granuloma in the rat. 4. Furthermore, decasilate had a significant mucolytic activity in rabbits and reduced the number of tussive seizures induced by an aerosol of citric acid in guinea-pigs. The pharmacological profile of decasilate suggests that it might be useful in the management of chronic bronchitis.
已使用不同实验模型评估了8-(2-苯乙基)-1-氧杂-二氮杂螺[4,5]癸烷-2-酮2-噻吩羧酸盐（癸硅酯，CAS 76652-72-7）的支气管解痉、抗过敏、抗炎、黏液溶解和镇咳活性。1. 癸硅酯在离体豚鼠气管制备物中对组胺诱导的收缩表现出显著的解痉活性，IC50为2.7×10⁻⁶mol/L。此外，口服癸硅酯（5 - 30mg·kg⁻¹）可显著减轻组胺气雾剂诱导的豚鼠支气管痉挛。2. 癸硅酯对致敏豚鼠回肠段抗原诱导的收缩有预防作用（EC50 8.0×10⁻⁶mol/L），并在抗原激发后添加时使其松弛（IC50 9.5×10⁻⁷mol/L）。3. 口服癸硅酯可显著减轻角叉菜胶和右旋糖酐诱导的大鼠后爪水肿，ED50值分别为169.5和34.5mg·kg⁻¹。然而，它对大鼠棉球诱导的肉芽肿无效。4. 此外，癸硅酯在兔体内具有显著的黏液溶解活性，并减少了柠檬酸气雾剂诱导的豚鼠咳嗽发作次数。癸硅酯的药理学特性表明它可能对慢性支气管炎的治疗有用。
