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Calcified Tissue International
Published in: Calcified Tissue International 4/2016

01-04-2016 | Review

Calcimimetic and Calcilytic Drugs: Feats, Flops, and Futures

Authors: E. F. Nemeth, W. G. Goodman

Published in: Calcified Tissue International | Issue 4/2016

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Abstract

The actions of extracellular Ca2+ in regulating parathyroid gland and kidney functions are mediated by the extracellular calcium receptor (CaR), a G protein-coupled receptor. The CaR is one of the essential molecules maintaining systemic Ca2+ homeostasis and is a molecular target for drugs useful in treating bone and mineral disorders. Ligands that activate the CaR are termed calcimimetics and are classified as either agonists (type I) or positive allosteric modulators (type II); calcimimetics inhibit the secretion of parathyroid hormone (PTH). Cinacalcet is a type II calcimimetic that is used to treat secondary hyperparathyroidism in patients receiving dialysis and to treat hypercalcemia in some forms of primary hyperparathyroidism. The use of cinacalcet among patients with secondary hyperparathyroidism who are managed with dialysis effectively lowers circulating PTH levels, reduces serum phosphorus and FGF23 concentrations, improves bone histopathology, and may diminish skeletal fracture rates and the need for parathyroidectomy. A second generation type II calcimimetic (AMG 416) is currently under regulatory review. Calcilytics are CaR antagonists that stimulate the secretion of PTH. Several calcilytic compounds have been evaluated as orally active anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because they lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders beyond those involving systemic Ca2+ homeostasis.
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Metadata
Title
Calcimimetic and Calcilytic Drugs: Feats, Flops, and Futures
Authors
E. F. Nemeth
W. G. Goodman
Publication date
01-04-2016
Publisher
Springer US
Published in
Calcified Tissue International / Issue 4/2016
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-015-0052-z

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