Cinacalcet hydrochloride (AMG-073 hydrochloride) is a naphthalene derivative and calcimimetic agent that enhances the sensitivity of parathyroid gland calcium-sensing receptors to serum calcium, thereby reducing parathyroid hormone secretion and decreasing serum calcium in the treatment of parathyroid diseases.

CaSR:2.8 μM(EC50)

Significant dose-dependent reductions in serum calcium levels were observed at 4, 8, and 24 hours post-oral administration of AMG-073 at dosages of 3, 10, and 30 mg/kg. A transient decrease in serum phosphorus levels was noted only with the highest dosage of AMG-073. Oral administration of Cinacalcet HCl at 1, 3, 10, and 30 mg/kg in 20% sulfobutylether-β-cyclodextrin sodium to normal rats induced a significant dose-dependent reduction in PTH levels within 1 to 4 hours. By 8 hours post-dosing, a significant reduction in PTH levels was observed with 10 and 30 mg/kg doses compared to the control group, with this effect dissipating after 24 hours. Additionally, an increase in calcitonin levels accompanying PTH suppression was observed with 40 mg/kg AMG-073 in rats. Similar to normal rats, a rapid dose-dependent reduction in PTH and calcium levels was noted in five out of six nephrectomized rats following oral AMG-073 administration. Furthermore, oral administration of 5 and 10 mg/kg Cinacalcet HCl for 4 weeks significantly reduced the weight of the parathyroid gland compared to the control group.

Cinacalcet HCl induces a concentration-dependent increase in cytoplasmic calcium levels in human embryonic kidney cells expressing the CaSR (Calcium-Sensing Receptor). Furthermore, in bovine parathyroid cells and a buffer containing 0.5 mM calcium, a concentration-dependent decrease in PTH (Parathyroid Hormone) levels was observed when treated with AMG 073 (Cinacalcet) concentrations ranging from 3 nM to 1 μM, achieving an IC50 of 27 nM.