NPS-2143 hydrochloride (NPS-2143 HCL) is a selective potent calcium ion-sensing receptor antagonist.

NPS 2143, even when tested at much higher concentrations (3 microM), did not affect the activity of a number of other G protein-coupled receptors, including those most structurally homologous to the Ca2+ receptor. NPS 2143 stimulated parathyroid hormone (PTH) secretion from bovine parathyroid cells (EC50 of 41 nM) over a range of extracellular Ca2+ concentrations and reversed the effects of the calcimimetic compound NPS R-467 on [Ca2+]i and on secretion of PTH . The first reported calcilytic compound was NPS 2143, an orally active molecule which elicits rapid, 3- to 4-fold increases in circulating levels of PTH.

When intravenously administered to normal rats, NPS 2143 swiftly elevated plasma PTH levels significantly. Known as calcilytics, substances like NPS 2143 act as Ca2+ receptor antagonists, with it being the inaugural compound (either atomic or molecular) identified with this activity [1]. Concurrent administration with an antiresorptive agent (estradiol) resulted in enhanced trabecular bone volume and bone mineral density in osteopenic rats.