Decker J E, Morrison N E, Lorenzo J A, Samour C M, McCarron B A, Raisz L G
University of Connecticut Health Center, Farmington 06032.
Calcif Tissue Int. 1989 Jan;44(1):61-4. doi: 10.1007/BF02556240.
Thionapthene-2-carboxylic acid (TNCA) was previously shown to lower serum calcium concentrations in hypercalcemic rats: however, oral administration of TNCA may cause gastric irritation. We have assessed thionapthene-2-carboxylic acid lysine salt (TNLY) for its effects on serum calcium concentration and survival in rats bearing the hypercalcemic Leydig cell tumor. TNLY (0.6-1.8 mmol/kg/day) produced a marked and prolonged dose-related decrease in serum calcium concentration. At the highest dose of 1.8 mmol/kg/day, hypocalcemia occurred. Effects were sustained for 96 hours or longer. In tumor-bearing rats that were not yet hypercalcemic, pretreatment with TNLY (0.9 mmol/kg/day) did not induce hypocalcemia and the onset of hypercalcemia was prevented. Neither TNLY nor dichloromethylene diphosphonate (CL2MDP), a potent inhibitor of bone resorption, significantly prolonged overall survival. We concluded that TNLY is a potent antihypercalcemic agent that warrants further testing for use in the treatment of hypercalcemic disorders.
硫茚-2-羧酸（TNCA）先前已被证明可降低高钙血症大鼠的血清钙浓度：然而，口服TNCA可能会引起胃部刺激。我们评估了硫茚-2-羧酸赖氨酸盐（TNLY）对患有高钙血症的睾丸间质细胞瘤大鼠血清钙浓度和存活率的影响。TNLY（0.6-1.8 mmol/kg/天）可使血清钙浓度显著且持续地呈剂量相关下降。在最高剂量1.8 mmol/kg/天时，出现了低钙血症。这种作用持续96小时或更长时间。在尚未出现高钙血症的荷瘤大鼠中，用TNLY（0.9 mmol/kg/天）预处理未诱发低钙血症，且预防了高钙血症的发生。TNLY和强力骨吸收抑制剂二氯亚甲基二膦酸盐（CL2MDP）均未显著延长总体生存期。我们得出结论，TNLY是一种有效的抗高钙血症药物，值得进一步测试以用于治疗高钙血症疾病。
