[Drugs inhibiting parathyroid hormone (PTH) secretion by control of the calcium receptor (calcimimetics)--effect on the set point of calcium-regulated PTH secretion].
Calcimimetics are positive allosteric modulators that activate the parathyroid calcium receptor (CaR) and thereby immediately suppress parathyroid hormone (PTH) secretion. Preclinical studies have demonstrated that calcimimetics inhibit PTH secretion and parathyroid gland hyperplasia and ameliorates bone qualities in rats with chronic renal insufficiency. Clinical trials with cinacalcet hydrochloride, a calcimimetic compound, have shown that calcimimetics possess lowering effects not only on serum PTH levels but also on serum phosphorus levels in dialysis patients with secondary hyperparathyroidism (2HPT). Thus, calcimimetics have considerable potential as an innovative medical approach to manage 2HPT. In this review, the similarities are extrapolated between the pharmacological effect of calcimimetics on the set point of Ca-regulated PTH secretion and clinical observations in affected subjects with activating CaR mutations.
Nagano
Nobuo
N
Medical Affairs Section, Pharmaceutical Division, Kirin Brewery Company, Limited, Japan.
D000818:Animals; D002118:Calcium / Q000502:physiology; D000069449:Cinacalcet; D002986:Clinical Trials as Topic; D003864:Depression, Chemical; D005799:Genes, Dominant; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy; D006996:Hypocalcemia / Q000503:physiopathology; D009154:Mutation; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000187:drug effects* / Q000235:genetics
D009281:Naphthalenes; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D010758:Phosphorus; D002118:Calcium; D000069449:Cinacalcet