calcimimetic

Calcimimetics are a class of drugs that act as allosteric activators of the calcium-sensing receptor (CaSR), a G-protein coupled receptor expressed mainly in the parathyroid gland and kidney. By increasing the receptor’s sensitivity to extracellular calcium, these agents suppress parathyroid hormone (PTH) secretion and lower serum calcium and phosphate levels. They are not calcium mimetics themselves; rather, they enhance CaSR activity to regulate calcium homeostasis.

Mechanistically, calcimimetics shift the CaSR calcium-response curve to the left, so smaller changes in extracellular calcium produce a stronger inhibitory signal on PTH release. In the kidney, CaSR activation reduces renal calcium reabsorption and modulates phosphate handling, contributing to lower serum calcium-phosphate products. The net effect is reduced PTH, lower bone turnover, and changes in calcium and phosphate balance.

Clinical use typically targets secondary hyperparathyroidism in chronic kidney disease, especially in patients on dialysis, where PTH elevations are common and difficult to control. Calcimimetics also have a role in managing hypercalcemia associated with parathyroid carcinoma or refractory primary hyperparathyroidism in select cases. Representative agents include cinacalcet, etelcalcetide (an intravenous peptide given after dialysis), and evocalcet (an oral agent used in various regions).

Adverse effects reflect the calcium-lowering action and include hypocalcemia, which requires monitoring of calcium levels. Other possible effects are nausea, vomiting, diarrhea, and fatigue. Drug interactions often arise with hepatic clearance pathways, particularly for oral agents, and dose adjustments may be needed in liver disease or concomitant therapies.