Calcimimetic agents and secondary hyperparathyroidism: treatment and prevention.
Calcimimetic agents and secondary hyperparathyroidism: treatment and prevention.
复制标题
拟钙剂和继发性甲状旁腺功能亢进症：治疗和预防。
DOI：
10.1093/ndt/17.2.204
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Goodman,WilliamG
中科院分区：
文献类型：
--
作者：
Goodman,WilliamG
拟钙剂是小的有机分子，其作为甲状旁腺和其他组织中钙敏感受体（CaSR）的变构激活剂。它们降低细胞外钙离子激活CaSR的阈值，并减少甲状旁腺细胞释放甲状旁腺激素（PTH）。通过靶向调节PTH分泌的分子机制，拟钙化合物提供了一种新的治疗多种临床疾病的方法，尽管有大量的体外和体内实验工作，但拟钙药物在人体中的经验相当有限。初步报告描述了它们在少数原发性甲状旁腺功能亢进患者和因终末期肾脏疾病而继发性甲状旁腺功能亢进患者中的应用（w2-4x）。尽管在已发表的研究中治疗的持续时间被限制在1或2周，但当给予正常志愿者或原发性或继发性甲状旁腺功能亢进患者时，拟钙化合物持续且可重复地降低血浆PTH水平。因此，人类早期临床试验的结果与实验动物w5 x中获得的数据一致。除了减少PTH分泌的作用外，拟钙化合物还可能从根本上影响甲状旁腺增生的过程，并且将其施用于实验动物可以有利地影响骨骼钙平衡。如果在人体中的研究证实，这些辅助功能的拟钙剂扩大其吸引力作为一种治疗方法继发性甲状旁腺功能亢进由于慢性肾功能衰竭。
Calcimimetic agents are small organic molecules that act as allosteric activators of the calcium sensing receptor (CaSR) in the parathyroid glands and other tissues. They lower the threshold for CaSR activation by extracellular calcium ions and diminish parathyroid hormone (PTH) release from parathyroid cells. By targeting the molecular mechanism that modulates PTH secretion on a minute-to-minute basis, calcimimetic compounds offer a novel approach to managing excess PTH secretion in several clinical disorders w1x.Despite abundant in vitro and in vivo experimental work, experience with calcimimetic agents in humans is rather limited. Preliminary reports describe their use in small numbers of patients with primary hyperparathyroidism and in somewhat larger numbers of patients with secondary hyperparathyroidism due to end-stage renal disease w2–4x. Although the duration of treatment in published studies has been confined to 1 or 2 weeks, calcimimetic compounds consistently and reproducibly lower plasma PTH levels when given to normal volunteers or to patients with either primary or secondary hyperparathyroidism. Results from early clinical trials in humans are consistent, therefore, with data obtained in experimental animals w5x. Apart from their effect to diminish PTH secretion, calcimimetic compounds may fundamentally influence the process of parathyroid gland hyperplasia, and their administration to experimental animals can favorably affect skeletal calcium balance. If confirmed by studies in humans, these ancillary features of calcimimetics broaden their appeal as a therapeutic approach to secondary hyperparathyroidism due to chronic renal failure.
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NPS R-568：一种II型拟钙化合物，作用于大鼠甲状旁腺细胞钙受体，降低甲状旁腺激素和钙的血浆水平。
影响因子：
3.5
作者：
J. Fox;S. H. Lowe;B. Petty;E. Nemeth
通讯作者：
E. Nemeth
影响因子：
19.6
作者：
Goodman, WG;Frazao, JM;Coburn, JW
通讯作者：
Coburn, JW
影响因子：
4.8
作者：
Li, YC;Amling, M;Demay, MB
通讯作者：
Demay, MB
甲状旁腺功能和 PTH 释放设定点：了解现有数据。
DOI：
10.1093/ndt/11.1.16
发表时间：
1996
期刊：
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
影响因子：
--
作者：
William G. Goodman;I. Salusky
通讯作者：
I. Salusky
影响因子：
5.8
作者：
BROWN, EM
通讯作者：
BROWN, EM