NPS-2143 hydrochloride (SB-262470A hydrochloride), an orally active calcilytic agent, is a selective and potent calcium ion-sensing receptor (CaSR) antagonist. NPS-2143 hydrochloride (SB-262470A hydrochloride) blocks increases in cytoplasmic Ca²⁺ concentrations (IC₅₀=43 nM) elicited by activating the Ca²⁺ receptor in HEK 293 cells expressing the human Ca²⁺ receptor^[1][2]. In Vitro: NPS-2143 hydrochloride (SB-262470A hydrochloride) stimulates parathyroid hormone (PTH) secretion from bovine parathyroid cells with EC₅₀ of 41 nM. Moreover, NPS-2143 hydrochloride also blocks the inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and the inhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cyclic AMP formation^[1]. In Vivo: When infused intravenously in normal rats, NPS-2143 hydrochloride (SB-262470A hydrochloride) causes a rapid and large increase in plasma levels of PTH. Ca²⁺ receptor antagonists are termed calcilytics and NPS-2143 is the first substance (either atomic or molecular) shown to possess such activity^[1].
When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats^[2].