Johannesson A J, Onkelinx C, Rodan G A, Raisz L G
Endocrinology. 1985 Oct;117(4):1508-11. doi: 10.1210/endo-117-4-1508.
Thiophene-2-carboxylic acid (TCA) was previously shown to be hypocalcemic in the rat. We have compared TCA with thionapthene-2-carboxylic acid (TNCA), an analog which is a more potent inhibitor of bone resorption in vitro, for the ability to decrease serum calcium concentration in vivo. In normocalcemic rats on a low calcium diet, TNCA (2 mmol/kg) produced a larger and more prolonged decrease in calcium concentration than TCA. In rats bearing the Walker 256 carcinosarcoma, which became hypercalcemic, TNCA produced a dose-related decrease in serum calcium concentration at 0.3-1.2 mmol/kg. TNCA reduced serum calcium concentration in 4-6 h, and the effects were sustained for up to 72 h. TNCA was effective after oral as well as sc administration. Unlike calcitonin which produced only a transient reduction in serum calcium followed by escape, the effects of TNCA (0.6 mmol/kg) were sustained for 1 week and were accompanied by a decrease in mortality in tumor-bearing animals. We conclude that TNCA is a potent hypocalcemic action which has a rapid and prolonged effect without evidence of escape. This and related compounds should be tested further for use in treatment of hypercalcemia and other states characterized by excessive bone resorption.
噻吩 -2- 羧酸（TCA）先前已被证明在大鼠中具有降钙作用。我们将 TCA 与硫茚 -2- 羧酸（TNCA）进行了比较，TNCA 是一种类似物，在体外是一种更强效的骨吸收抑制剂，比较它们在体内降低血清钙浓度的能力。在低钙饮食的正常血钙大鼠中，TNCA（2 mmol/kg）比 TCA 导致更大且更持久的钙浓度降低。在患有 Walker 256 癌肉瘤且血钙升高的大鼠中，TNCA 在 0.3 - 1.2 mmol/kg 剂量下使血清钙浓度呈剂量相关下降。TNCA 在 4 - 6 小时内降低血清钙浓度，且效果可持续长达 72 小时。TNCA 口服和皮下给药均有效。与降钙素不同，降钙素只会使血清钙短暂降低然后出现逃逸现象，而 TNCA（0.6 mmol/kg）的效果可持续 1 周，并伴有荷瘤动物死亡率降低。我们得出结论，TNCA 具有强大的降钙作用，起效迅速且持久，无逃逸迹象。这种及相关化合物应进一步测试，以用于治疗高钙血症和其他以骨吸收过多为特征的病症。
