R 568 hydrochloride is a kind of calcimimetic agent which can changed the structural conformation of the calcium-sensing receptor (CaSR) and stereo-selectively increased its sensitivity to extracellular Ca2+ [1]. R 568 hydrochloride, as a phenylalkylamine derivative of calcimimetics, has been subjected to clinical trials and shown a dose-dependent decrease in the levels of parathyroid hormone (PTH) [2].
R 568 hydrochloride (1μM; 4h) significantly upregulated IL-8 expression in HT29CaSR-GFP cells; R 568 hydrochloride (1μM; 4h) significantly upregulated the expression of COX-2 and PGES-1 [3].
R 568 hydrochloride (20μmol/kg; 8weeks; s.c.) decreased the blood urea nitrogen (BUN) levels of Sprague-Dawley (SD) rats with uremic; R 568 hydrochloride (20μmol/kg; 8weeks; s.c.) suppressed the increase in parathyroid gland volume of SD rats with uremic [4]. R 568 hydrochloride (3, 30mg/kg; 16d; p.o.) reduced serum PTH levels of SD rats which subjected to a partial nephrectomy [5]. R 568 hydrochloride (0.5, 1.0, 2.5 and 5.0mg/kg; 30min; i.v.) decreased plasma Ca2+ concentration in Wistar rats [6].
References:
[1] Ureña P, Frazão J M. Calcimimetic agents: review and perspectives [J]. Kidney international Supplement, 2003, (85): S91-S96.
[2] Wada M, Furuya Y, Sakiyama J, et al. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor [J]. The Journal of clinical investigation, 1997, 100(12): 2977-2983.
[3] Gushchina V, Kupper N, Schwarzkopf M, et al. The calcium-sensing receptor modulates the prostaglandin E2 pathway in intestinal inflammation [J]. Frontiers in pharmacology, 2023, 14: 1151144.
[4] Wada M, Nagano N, Furuya Y, et al. Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism [J]. Kidney international, 2000, 57(1): 50-58.
[5] Wada M, Ishii H, Furuya Y, et al. NPS R-568 halts or reverses osteitis fibrosa in uremic rats [J]. Kidney international, 1998, 53(2): 448-453.
[6] Rybczyńska A, Boblewski K, Lehmann A, et al. Pharmacological activity of calcimimetic NPS R-568 administered intravenously in rats: dose dependency [J]. Pharmacological reports, 2006, 58(4): 533-539.
R 568 hydrochloride是一种能改变钙敏感受体（CaSR）结构构象，立体选择性地提高其对细胞外Ca2+敏感性的拟钙剂[1]。R 568 hydrochloride作为一种苯基烷基胺衍生物类的拟钙剂，已经在临床上证明对甲状旁腺激素有剂量依赖性降低的作用[2]。
R 568 hydrochlorid（1μM；4h）显著上调HT29CaSR−GFP细胞中IL-8的表达水平；R 568 hydrochlorid（1μM；4h）显著上调HT29CaSR−GFP细胞中COX-2和PGES-1的表达水平[3]。
R 568 hydrochlorid（20μmol/kg；8weeks；s.c.）降低尿毒症SD（Sprague-Dawley）大鼠模型BUN（blood urea nitrogen）水平；R 568 hydrochlorid（20μmol/kg；8weeks；s.c.）抑制尿毒症SD大鼠模型的甲状旁腺腺体体积的增加[4]。R 568 hydrochlorid（3、30mg/kg；16d；p.o.）降低接受肾部分切除手术的SD大鼠血清中的甲状旁腺激素水平[5]；R 568 hydrochloride（0.5、1.0、2.5和5.0mg/kg；30min；i.v.）降低Wistar大鼠血浆中的Ca2+浓度[6]；