Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. Etelcalcetide was approved (trade name Parsabiv) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis in February, 2017. Etelcalcetide is a synthetic peptide calcium-sensing receptor agonist. It allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.

Cinacalcet is a positive allosteric modulator of calcium sensing receptor. The drug is approved by FDA (Sensipar trade name) and used for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on dialysis; hypercalcemia in adult patients with parathyroid carcinoma; hypercalcemia in adult patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy.

Tecalcet (also known as KRN-568; NPS-R-568; R-568), is an oral calcium channel agonist potentially for the treatment of hyperparathyroidism. Calcimimetics, such as Tecalcet, are agonists and activate the calcium channel in a non-competitive fashion. Tecalcet does not compete directly with calcium that activates the receptor through binding in the extracellular domain of these receptors, but rather, calcimimetics such as Tecalcet, bind allosterically in the seven transmembranes to ‘sensitize’ the receptor to extracellular calcium. Tecalcet acts as an agonist of the calcium receptors of the parathyroid cells, causing a decrease in PTH release. Tecalcet also acts on the parafollicular cells (C-cells) of the thyroid gland, resulting in an increase in calcitonin release. These effects ultimately lead to a decrease in plasma calcium concentrations. Studies in rats have shown that oral administration of R-568 at doses ranging from 3 to 100 mg/kg caused a rapid (<30 minutes) decrease in plasma PTH concentrations and an increase in calcitonin concentrations, accompanied by a dose-dependent decrease in calcium concentrations. Tecalcet had been in phase II clinical trials by for the treatment of hyperparathyroidism, postmenopausal osteoporosis and rheumatic disorders in Japan and US. Development of Tecalcet has been discontinued.

NPS-2143 is a novel potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. Blockage of CaSR with NPS-2143 has being shown to prevent the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents. When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats.

Monocrotaline is an 11-membered macrocyclic pyrrolizidine alkaloid derived from the seeds of the Crotalaria spectabilis plant. Monocrotaline is activated to the reactive pyrrole metabolite dehydromonocrotaline in the liver, a reaction that is highly dependent on cytochrome P-450 (CYP3A4). Monocrotaline induces a syndrome characterized, among other manifestations, by pulmonary hypertension, pulmonary mononuclear vasculitis (acute necrotizing pulmonary arteritis in about one-third of the animals), and right ventricular hypertrophy. Monocrotaline is widely used to model pulmonary arterial hypertension in rodents. Monocrotaline aggregates on and activates the extracellular calcium-sensing receptor (CaSR) of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.

Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. Etelcalcetide was approved (trade name Parsabiv) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis in February, 2017. Etelcalcetide is a synthetic peptide calcium-sensing receptor agonist. It allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.

Cinacalcet is a positive allosteric modulator of calcium sensing receptor. The drug is approved by FDA (Sensipar trade name) and used for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on dialysis; hypercalcemia in adult patients with parathyroid carcinoma; hypercalcemia in adult patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy.

Tecalcet (also known as KRN-568; NPS-R-568; R-568), is an oral calcium channel agonist potentially for the treatment of hyperparathyroidism. Calcimimetics, such as Tecalcet, are agonists and activate the calcium channel in a non-competitive fashion. Tecalcet does not compete directly with calcium that activates the receptor through binding in the extracellular domain of these receptors, but rather, calcimimetics such as Tecalcet, bind allosterically in the seven transmembranes to ‘sensitize’ the receptor to extracellular calcium. Tecalcet acts as an agonist of the calcium receptors of the parathyroid cells, causing a decrease in PTH release. Tecalcet also acts on the parafollicular cells (C-cells) of the thyroid gland, resulting in an increase in calcitonin release. These effects ultimately lead to a decrease in plasma calcium concentrations. Studies in rats have shown that oral administration of R-568 at doses ranging from 3 to 100 mg/kg caused a rapid (<30 minutes) decrease in plasma PTH concentrations and an increase in calcitonin concentrations, accompanied by a dose-dependent decrease in calcium concentrations. Tecalcet had been in phase II clinical trials by for the treatment of hyperparathyroidism, postmenopausal osteoporosis and rheumatic disorders in Japan and US. Development of Tecalcet has been discontinued.

NPS-2143 is a novel potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. Blockage of CaSR with NPS-2143 has being shown to prevent the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents. When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats.

Monocrotaline is an 11-membered macrocyclic pyrrolizidine alkaloid derived from the seeds of the Crotalaria spectabilis plant. Monocrotaline is activated to the reactive pyrrole metabolite dehydromonocrotaline in the liver, a reaction that is highly dependent on cytochrome P-450 (CYP3A4). Monocrotaline induces a syndrome characterized, among other manifestations, by pulmonary hypertension, pulmonary mononuclear vasculitis (acute necrotizing pulmonary arteritis in about one-third of the animals), and right ventricular hypertrophy. Monocrotaline is widely used to model pulmonary arterial hypertension in rodents. Monocrotaline aggregates on and activates the extracellular calcium-sensing receptor (CaSR) of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.