[Calcimimetics--a new treatment for hyperparathyroidism?].
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.
Piecha
Grzegorz
G
Klinika Nefrologii, Endokrynologii i Chorób Przemiany Materii Slaskiej Akademii Medycznej w Katowicach.
Chudek
Jerzy
J
Wiecek
Andrzej
A
D000495:Allosteric Site / Q000187:drug effects; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000819:agonists*; D002135:Calcium-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D000069449:Cinacalcet; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000378:metabolism; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D000814:Aniline Compounds; D002135:Calcium-Binding Proteins; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; C111654:NPS R-467; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing; D002118:Calcium; D000069449:Cinacalcet