The Ca(2+) receptor on the surface of parathyroid cells is the primary molecular entity regulating secretion of parathyroid hormone (PTH). Because of this, it is a particularly appealing target for new drugs intended to increase or decrease circulating levels of PTH. Calcilytic compounds are Ca(2+) receptor antagonists which increase the 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. These rapid changes in plasma PTH levels are sufficient to increase bone turnover in ovariectomized, osteopenic rats. When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats. The magnitude of these changes are far in excess of those caused by estradiol alone and are comparable with those achieved by daily administration of PTH or a peptide analog. These anabolic effects of NPS 2143 on bone are not associated with hyperplasia of the parathyroid glands. Calcilytic compounds can increase endogenous levels of circulating PTH to an extent that stimulates new bone formation. Such compounds could replace the use of exogenous PTH or its peptide fragments in treating osteoporosis.

This article has been cited by other articles:

				E. F. Nemeth Anabolic Therapy for Osteoporosis: Calcilytics IBMS BoneKEy, June 1, 2008; 5(6): 196 - 208. [Abstract] [Full Text] [PDF]

				S. Lorenz, R. Frenzel, R. Paschke, G. E. Breitwieser, and S. U. Miedlich Functional Desensitization of the Extracellular Calcium-Sensing Receptor Is Regulated via Distinct Mechanisms: Role of G Protein-Coupled Receptor Kinases, Protein Kinase C and {beta}-Arrestins Endocrinology, May 1, 2007; 148(5): 2398 - 2404. [Abstract] [Full Text] [PDF]

				Y. Huang and G. E. Breitwieser Rescue of Calcium-sensing Receptor Mutants by Allosteric Modulators Reveals a Conformational Checkpoint in Receptor Biogenesis J. Biol. Chem., March 30, 2007; 282(13): 9517 - 9525. [Abstract] [Full Text] [PDF]

				B. J. Arey, R. Seethala, Z. Ma, A. Fura, J. Morin, J. Swartz, V. Vyas, W. Yang, J. K. Dickson Jr., and J. H. M. Feyen A Novel Calcium-Sensing Receptor Antagonist Transiently Stimulates Parathyroid Hormone Secretion in Vivo Endocrinology, April 1, 2005; 146(4): 2015 - 2022. [Abstract] [Full Text] [PDF]

				J. Hu, S. J. McLarnon, S. Mora, J. Jiang, C. Thomas, K. A. Jacobson, and A. M. Spiegel A Region in the Seven-transmembrane Domain of the Human Ca2+ Receptor Critical for Response to Ca2+ J. Biol. Chem., February 11, 2005; 280(6): 5113 - 5120. [Abstract] [Full Text] [PDF]

				T. M. Murray, L. G. Rao, P. Divieti, and F. R. Bringhurst Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl- Terminal Ligands Endocr. Rev., February 1, 2005; 26(1): 78 - 113. [Abstract] [Full Text] [PDF]

				J. E. Cohen and R. D. Fields Extracellular Calcium Depletion in Synaptic Transmission Neuroscientist, February 1, 2004; 10(1): 12 - 17. [Abstract] [PDF]

				E. F. Nemeth, W. H. Heaton, M. Miller, J. Fox, M. F. Balandrin, B. C. Van Wagenen, M. Colloton, W. Karbon, J. Scherrer, E. Shatzen, et al. Pharmacodynamics of the Type II Calcimimetic Compound Cinacalcet HCl J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 627 - 635. [Abstract] [Full Text] [PDF]

				C. Petrel, A. Kessler, F. Maslah, P. Dauban, R. H. Dodd, D. Rognan, and M. Ruat Modeling and Mutagenesis of the Binding Site of Calhex 231, a Novel Negative Allosteric Modulator of the Extracellular Ca2+-sensing Receptor J. Biol. Chem., December 5, 2003; 278(49): 49487 - 49494. [Abstract] [Full Text] [PDF]