Abstract | BACKGROUND: Recognition of the role of the extracellular calcium-sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in the extracellular ionized calcium (ec(Ca2+)) regulates PTH, calcitonin secretion, urinary calcium excretion, and, ultimately, bone turnover. METHODS: The cloning of the CaR and the discovery of mutations that make the receptor less or more sensitive to calcium have allowed a better understanding of several hereditary disorders characterized by either hyperparathyroidism or hypoparathyroidism. The CaR, able to amplify the sensitivity of the CaR to Ca++ and suppress PTH levels with a resulting decrease in blood Ca++, became an ideal target for the development of compounds, the calcimimetics. Experience with the calcimimetic R-568 in patients with primary and secondary hyperparathyroidism and parathyroid carcinoma are summarized. RESULTS: The first clinical studies with the first-generation calcimimetic agents have demonstrated their efficacy in lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low bioavailability of these first calcimimetics predicts a difficult clinical utilization. The second-generation calcimimetic, AMG 073, having a better pharmacokinetic profile, appears to be effective and safe for the treatment of secondary hyperparathyroidism, suppressing PTH levels while simultaneously reducing serum phosphorus levels and the calcium x phosphorus product. CONCLUSION:
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Authors | Pablo Ureña, João M Frazão |
Journal | Kidney international. Supplement
(Kidney Int Suppl)
Issue 85
Pg. S91-6
(Jun 2003)
ISSN: 0098-6577 [Print] United States |
PMID | 12753275
(Publication Type: Journal Article, Review)
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Chemical References |
- Aniline Compounds
- N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
- Parathyroid Hormone
- Phenethylamines
- Propylamines
- Receptors, Calcium-Sensing
- Calcium
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Topics |
- Aniline Compounds
(pharmacokinetics, therapeutic use)
- Animals
- Calcium
(physiology)
- Clinical Trials as Topic
- Humans
- Hyperparathyroidism, Secondary
(drug therapy)
- Kidney Failure, Chronic
(complications)
- Parathyroid Hormone
(metabolism)
- Phenethylamines
- Propylamines
- Receptors, Calcium-Sensing
(drug effects, physiology)
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