Rybczyńska Apolonia, Hoppe Anzelm
Katedra i Zakład Fizjopatologii, Akademia Medyczna w Gdańsku.
Przegl Lek. 2003;60(6):418-24.
Treatment of excessive secretion of parathyroid hormone (PTH) in primary hyperparathyroidism (I degree HPT) as well as in secondary hyperparathyroidism (II degree HPT) in chronic renal insufficiency is symptomatic, short-term acting and far from expectations. Recognition of properties of calcium receptor (CaR) expressed on parathyroid principal cell membranes created possibilities to explore new compounds that could alter directly PTH secretion and provide a novel therapy for direct correction of increased secretion of the hormone in these disorders. Ligands that activate this receptor and inhibit PTH secretion are called calcimimetics. Recently clinical trials with NPS R-568, a calcimimetic of the Ist generation, and AMG 073, a representative of calcimimetics of IInd generation, were completed. Calcimimetics, taken orally, effectively lower increased secretion of PTH and hypercalcemia in I degree HPT, by "pharmacologic parathyroidectomy". Such compounds are also safe and effective in dialysed patients with II degree HPT in chronic renal insufficiency: they decrease PTH plasma level and prevent parathyroid cell hyperplasia. The other compounds, called calcilytics and represented by NPS 2143, inhibit CaR resulting therefore in increase of PTH secretion. Administration of calcilytics would provide a valuable alternative to inhibit progression of osteoporosis. Subcutaneous, pulsative low doses of recombinant PTH (ALX1-11) administration induces increase of bone formation. Such an effect to some extent was obtained by transient increase of endogenous PTH secretion induced by oral administration of calcilytic NPS 2143 to osteopenic ovariectomized rats, especially if it was accompanied by supplementation of estrogens.
治疗原发性甲状旁腺功能亢进症（I度HPT）以及慢性肾功能不全继发性甲状旁腺功能亢进症（II度HPT）中甲状旁腺激素（PTH）分泌过多的方法具有对症性、短期作用且远未达预期。对甲状旁腺主细胞膜上表达的钙受体（CaR）特性的认识为探索能够直接改变PTH分泌的新化合物创造了可能性，并为直接纠正这些疾病中激素分泌增加提供了新的治疗方法。激活该受体并抑制PTH分泌的配体被称为拟钙剂。最近，第一代拟钙剂NPS R - 568和第二代拟钙剂代表AMG 073的临床试验已经完成。口服拟钙剂通过“药物性甲状旁腺切除术”有效降低I度HPT中PTH分泌增加和高钙血症。这类化合物在慢性肾功能不全的II度HPT透析患者中也安全有效：它们可降低血浆PTH水平并预防甲状旁腺细胞增生。其他化合物，称为钙敏感受体拮抗剂，以NPS 2143为代表，抑制CaR，从而导致PTH分泌增加。给予钙敏感受体拮抗剂将为抑制骨质疏松症进展提供有价值的替代方法。皮下脉冲式低剂量给予重组PTH（ALX1 - 11）可诱导骨形成增加。通过向骨质疏松的去卵巢大鼠口服钙敏感受体拮抗剂NPS 2143诱导内源性PTH分泌短暂增加，在一定程度上获得了这样的效果，尤其是在补充雌激素的情况下。
