Negri Armando L, Slatopolsky Eduardo A
Instituto de Investigaciones Metabólicas, Facultad de Medicina Universidad del Salvador, Buenos Aires, Argentina.
Medicina (B Aires). 2003;63(2):165-71.
The recent discovery and cloning of the extra cellular calcium sensing receptor (CaSR) has allowed a better understanding of the regulation of normal calcium metabolism and of rare disturbances in mineral metabolism. In the parathyroid glands the CaSR is responsible for modulating parathyroid hormone release as a function of the extra cellular calcium level. This discovery has allowed the development of drugs that mimics or potentiates the actions of extra cellular calcium on the CaSR, called calcimimetics that decrease parathyroid hormone secretion without increasing serum calcium. The new calcimimetics are small organic molecules that act as allosteric activators of the CaSR and they are in their initial face of clinical development. Although the experience with these drugs is limited, they have shown to effectively lower parathyroid hormone levels in patients with hyperparathyroidism secondary to end-stage renal failure without inducing important side-effects. Thus calcimimetic compounds have considerable potential as new drugs for the treatment of secondary hyperparathyroidism and uremic bone disease.
细胞外钙敏感受体(CaSR)的近期发现与克隆,使人们能更好地理解正常钙代谢的调节以及矿物质代谢中罕见紊乱的情况。在甲状旁腺中,CaSR负责根据细胞外钙水平调节甲状旁腺激素的释放。这一发现促使了一类药物的研发,这类药物可模拟或增强细胞外钙对CaSR的作用,被称为拟钙剂,它能降低甲状旁腺激素分泌而不升高血清钙。新型拟钙剂是作为CaSR变构激活剂的小分子有机化合物,目前正处于临床研发初期。尽管使用这些药物的经验有限,但它们已显示出能有效降低终末期肾衰竭继发性甲状旁腺功能亢进患者的甲状旁腺激素水平,且不会引发严重副作用。因此,拟钙剂化合物作为治疗继发性甲状旁腺功能亢进和尿毒症性骨病的新药具有相当大的潜力。