Thionapthene-2-carboxylic acid: a new antihypercalcemic agent.
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.
D000284:Administration, Oral; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology; D002264:Carboxylic Acids; D002279:Carcinoma 256, Walker / Q000150:complications / Q000378:metabolism; D006934:Hypercalcemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D002264:Carboxylic Acids; D013876:Thiophenes; C550746:2-thiophene carboxylic acid; D002116:Calcitonin; C026163:benzo(b)thiophene-2-carboxylic acid