Franzone J S, Cirillo R, Reboani M C
Research Laboratories, Istituto Biologico Chemioterapico ABC S.p.A., Turin, Italy.
Int J Tissue React. 1991;13(3):131-8.
This paper contributes to the pharmacological profile of doxofylline (Ansimar), a new xanthine derivative with high antibronchospastic activity and no extrapulmonary or cardiac side-effects, clearly demonstrating its inability to mobilize intracellular calcium stores, unlike other xanthines. In vitro, doxofylline does not cause rabbit ear artery contraction under Ca(++)-free conditions. In vivo, doxofylline does not induce a decrease in the calcium concentration of rabbit washed blood platelets. In the same trials theophylline showed opposite results. Furthermore, doxofylline does not antagonize receptors of Ca-antagonists, and does not interfere with the influx of calcium into the cell. Doxofylline also has a very low affinity for adenosine receptors inhibiting cAMP-phosphodiesterase as does theophylline. The absence of typical methylxanthine side-effects is undoubtedly due to doxofylline's low affinity for adenosine receptors, although this does not explain the absence of cardiovascular effects. The present study presents clear evidence that the inability of doxofylline to cause positive inotropism can be linked to its inability to induce calcium movement from intracellular stores.
本文对多索茶碱（安赛玛）的药理学特性进行了研究。多索茶碱是一种新型黄嘌呤衍生物，具有高抗支气管痉挛活性，且无肺外或心脏副作用。与其他黄嘌呤不同，它明显无法动员细胞内钙储备。在体外，多索茶碱在无Ca(++)条件下不会引起兔耳动脉收缩。在体内，多索茶碱不会导致兔洗涤血小板钙浓度降低。在相同试验中，茶碱显示出相反的结果。此外，多索茶碱不拮抗钙拮抗剂的受体，也不干扰钙流入细胞。多索茶碱对腺苷受体的亲和力也很低，与茶碱一样能抑制环磷酸腺苷磷酸二酯酶。多索茶碱不存在典型的甲基黄嘌呤副作用，这无疑归因于其对腺苷受体的低亲和力，尽管这并不能解释其无心血管效应的原因。本研究提供了明确证据，表明多索茶碱无法引起正性肌力作用与它无法诱导细胞内钙储备的钙移动有关。
