[Basic and clinical aspects of calcimimetics. Discovery and development of calcimimetics]

Parathyroid cells can sense small fluctuations in plasma calcium ion (Ca(2 + )) levels by virtue of a cell surface calcium receptor (CaR) that belongs to superfamily of G-protein-coupled receptors. Dr. Nemeth and his colleagues discovered that certain phenylalkylamine compounds stereo-selectively increased intracellular Ca(2 + ) concentration and inhibited parathyroid hormone (PTH) secretion in cultured bovine parathyroid cells. Calcimimetics are positive allosteric modulators that activate the parathyroid CaR and thereby immediately suppress PTH secretion. Cinacalcet hydrochloride (cinacalcet) , which was approved by the FDA in 2004 as the first calcimimetics drug, has just been approved in Japan for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease on dialysis. Clinical trials have shown that cinacalcet has considerable potential as an innovative medical approach to manage SHPT. Thus, the true value of this medicine will be finally evaluated by the Japanese dialysis medical scene.