[Calcimimetics--a new treatment for hyperparathyroidism?]

Pol Merkur Lekarski. 2005 May;18(107):581-4.
[Article in Polish]

Abstract

The common feature of both primary and secondary hyperparathyroidism despite differences in their etiopathogenesis is excess parathormone (PTH) secretion. Calcium sensing receptor (CaR) belongs to G-protein coupled receptors superfamily and plays central role in the regulation of PTH secretion. Mutations in receptor's gene lead to PTH suppression set-point shift into higher (familial benign hypocalciuric hypercalcemia) or lower Ca2+ levels (familial hypercalciuric hypocalcemia). Calcimimetics are a new class of drugs which increase the CaR response to agonist binding by allosteric conformation modification. First generation calcimimetics: NPS R-467 and NPS R-568 revealed their effectiveness in PTH suppression in experimental animal model. Short-term trials with NPS R-568 used in people with primary or secondary hyperparathyroidism confirmed significant PTH suppression. In further clinical trials a second generation calcimimetic: AMG 073 was used. AMG 073 intake was related to decrease of serum PTH and phosphorus concentrations and Ca x P product suppression with low number of hypocalcemia or other side effects. In the future calcimimetics could be an alternative to vitamin D active metabolites or analogs treatment and to surgical procedures.

Publication types

  • Review

MeSH terms

  • Allosteric Site / drug effects
  • Aniline Compounds / pharmacology*
  • Animals
  • Calcium / agonists*
  • Calcium-Binding Proteins / drug effects*
  • Calcium-Binding Proteins / metabolism
  • Cinacalcet
  • Humans
  • Hyperparathyroidism / drug therapy*
  • Hyperparathyroidism / metabolism
  • Naphthalenes / pharmacology*
  • Parathyroid Hormone / metabolism
  • Phenethylamines
  • Propylamines
  • Receptors, Calcium-Sensing / drug effects*
  • Receptors, Calcium-Sensing / metabolism
  • Treatment Outcome

Substances

  • Aniline Compounds
  • Calcium-Binding Proteins
  • N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
  • NPS R-467
  • Naphthalenes
  • Parathyroid Hormone
  • Phenethylamines
  • Propylamines
  • Receptors, Calcium-Sensing
  • Calcium
  • Cinacalcet