The effects of thionapthene-2-carboxylic acid-lysine on the hypercalcemia of malignancy in the rat.

Abstract

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.

• Authors: J E Decker, N E Morrison, J A Lorenzo, C M Samour, B A McCarron, L G Raisz
• Journal: Calcified tissue international (Calcif Tissue Int) Vol. 44 Issue 1 Pg. 61-4 (Jan 1989) ISSN: 0171-967X [Print] United States
• PMID: 2521808 (Publication Type: Journal Article)

Chemical References

• Thiophenes
• Clodronic Acid
• thionapthene-2-carboxylic acid-lysine
• Lysine
• Calcium

Topics

• Animals
• Bone Resorption (drug effects)
• Calcium (blood)
• Clodronic Acid (pharmacology)
• Hypercalcemia (drug therapy, etiology)
• Leydig Cell Tumor (complications, metabolism)
• Lysine (analogs & derivatives, pharmacology, therapeutic use)
• Male
• Rats
• Rats, Inbred F344
• Thiophenes (pharmacology, therapeutic use)