Calcilytics are pharmaceutical drugs that act as antagonists at the calcium-sensing receptor (CaSR). This increases the secretion of parathyroid hormone (PTH), which has a temporary anabolic effect on bone tissue, producing an increase in both bone volume and bone density due to increased bone deposition and resorption. However, long term use of these causes resorption, degrading the bone to raise blood calcium. [1] Consequently, these drugs have been researched for the treatment of osteoporosis, [2] [3] [4] though with only limited success. [5] More recent research has suggested a number of additional applications for these drugs, such as hyperresponsiveness and inflammation in allergic asthma. [6] [7] [8] [9]
Examples
References
- ^ Boron WF, Boulpaep EL (2012). Medical Physiology (2nd ed.). Elsevier Health Sciences. p. 817. ISBN 978-1-4557-1181-9.
- ^ Nemeth EF (August 2002). "The search for calcium receptor antagonists (calcilytics)". Journal of Molecular Endocrinology. 29 (1): 15–21. doi: 10.1677/jme.0.0290015. PMID 12200226.
- ^ Silver J, Bushinsky D (July 2004). "Harnessing the parathyroids to create stronger bones". Current Opinion in Nephrology and Hypertension. 13 (4): 471–6. doi: 10.1097/01.mnh.0000133984.47806.00. PMID 15199299. S2CID 12507535.
- ^ Widler L (April 2011). "Calcilytics: antagonists of the calcium-sensing receptor for the treatment of osteoporosis". Future Medicinal Chemistry. 3 (5): 535–47. doi: 10.4155/fmc.11.17. PMID 21526895.
- ^ Nemeth EF, Shoback D (June 2013). "Calcimimetic and calcilytic drugs for treating bone and mineral-related disorders". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (3): 373–84. doi: 10.1016/j.beem.2013.02.008. PMID 23856266.
- ^ Kim JY, Ho H, Kim N, Liu J, Tu CL, Yenari MA, Chang W (November 2014). "Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection". Annals of Clinical and Translational Neurology. 1 (11): 851–66. doi: 10.1002/acn3.118. PMC 4265057. PMID 25540800.
- ^ Aggarwal A, Prinz-Wohlgenannt M, Tennakoon S, Höbaus J, Boudot C, Mentaverri R, Brown EM, Baumgartner-Parzer S, Kállay E (September 2015). "The calcium-sensing receptor: A promising target for prevention of colorectal cancer". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1853 (9): 2158–67. doi: 10.1016/j.bbamcr.2015.02.011. PMC 4549785. PMID 25701758.
- ^ Dal Prà I, Chiarini A, Armato U (February 2015). "Antagonizing amyloid-β/calcium-sensing receptor signaling in human astrocytes and neurons: a key to halt Alzheimer's disease progression?". Neural Regeneration Research. 10 (2): 213–8. doi: 10.4103/1673-5374.152373. PMC 4392667. PMID 25883618.
- ^ Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, P Lowe AP, et al. (April 2015). "Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma". Science Translational Medicine. 7 (284): 284ra60. doi: 10.1126/scitranslmed.aaa0282. PMC 4725057. PMID 25904744.
- ^ a b c Letz S, Haag C, Schulze E, Frank-Raue K, Raue F, Hofner B, Mayr B, Schöfl C (2014). "Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia". PLOS ONE. 9 (12): e115178. Bibcode: 2014PLoSO...9k5178L. doi: 10.1371/journal.pone.0115178. PMC 4266668. PMID 25506941.
Calcilytics are pharmaceutical drugs that act as antagonists at the calcium-sensing receptor (CaSR). This increases the secretion of parathyroid hormone (PTH), which has a temporary anabolic effect on bone tissue, producing an increase in both bone volume and bone density due to increased bone deposition and resorption. However, long term use of these causes resorption, degrading the bone to raise blood calcium. [1] Consequently, these drugs have been researched for the treatment of osteoporosis, [2] [3] [4] though with only limited success. [5] More recent research has suggested a number of additional applications for these drugs, such as hyperresponsiveness and inflammation in allergic asthma. [6] [7] [8] [9]
Examples
References
- ^ Boron WF, Boulpaep EL (2012). Medical Physiology (2nd ed.). Elsevier Health Sciences. p. 817. ISBN 978-1-4557-1181-9.
- ^ Nemeth EF (August 2002). "The search for calcium receptor antagonists (calcilytics)". Journal of Molecular Endocrinology. 29 (1): 15–21. doi: 10.1677/jme.0.0290015. PMID 12200226.
- ^ Silver J, Bushinsky D (July 2004). "Harnessing the parathyroids to create stronger bones". Current Opinion in Nephrology and Hypertension. 13 (4): 471–6. doi: 10.1097/01.mnh.0000133984.47806.00. PMID 15199299. S2CID 12507535.
- ^ Widler L (April 2011). "Calcilytics: antagonists of the calcium-sensing receptor for the treatment of osteoporosis". Future Medicinal Chemistry. 3 (5): 535–47. doi: 10.4155/fmc.11.17. PMID 21526895.
- ^ Nemeth EF, Shoback D (June 2013). "Calcimimetic and calcilytic drugs for treating bone and mineral-related disorders". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (3): 373–84. doi: 10.1016/j.beem.2013.02.008. PMID 23856266.
- ^ Kim JY, Ho H, Kim N, Liu J, Tu CL, Yenari MA, Chang W (November 2014). "Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection". Annals of Clinical and Translational Neurology. 1 (11): 851–66. doi: 10.1002/acn3.118. PMC 4265057. PMID 25540800.
- ^ Aggarwal A, Prinz-Wohlgenannt M, Tennakoon S, Höbaus J, Boudot C, Mentaverri R, Brown EM, Baumgartner-Parzer S, Kállay E (September 2015). "The calcium-sensing receptor: A promising target for prevention of colorectal cancer". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1853 (9): 2158–67. doi: 10.1016/j.bbamcr.2015.02.011. PMC 4549785. PMID 25701758.
- ^ Dal Prà I, Chiarini A, Armato U (February 2015). "Antagonizing amyloid-β/calcium-sensing receptor signaling in human astrocytes and neurons: a key to halt Alzheimer's disease progression?". Neural Regeneration Research. 10 (2): 213–8. doi: 10.4103/1673-5374.152373. PMC 4392667. PMID 25883618.
- ^ Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, P Lowe AP, et al. (April 2015). "Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma". Science Translational Medicine. 7 (284): 284ra60. doi: 10.1126/scitranslmed.aaa0282. PMC 4725057. PMID 25904744.
- ^ a b c Letz S, Haag C, Schulze E, Frank-Raue K, Raue F, Hofner B, Mayr B, Schöfl C (2014). "Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia". PLOS ONE. 9 (12): e115178. Bibcode: 2014PLoSO...9k5178L. doi: 10.1371/journal.pone.0115178. PMC 4266668. PMID 25506941.