The effects of thionapthene-2-carboxylic acid-lysine on the hypercalcemia of malignancy in the rat.
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.
Decker
J E
JE
University of Connecticut Health Center, Farmington 06032.
Morrison
N E
NE
Lorenzo
J A
JA
Samour
C M
CM
McCarron
B A
BA
Raisz
L G
LG
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002118:Calcium / Q000097:blood; D004002:Clodronic Acid / Q000494:pharmacology; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D007984:Leydig Cell Tumor / Q000150:complications / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
D013876:Thiophenes; D004002:Clodronic Acid; C058657:thionapthene-2-carboxylic acid-lysine; D008239:Lysine; D002118:Calcium