Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0221002 (primary hyperparathyroidism)
4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:[Calcimimmetic and calcilytics: new perspectives of correction of abnormal parathormone (PTH) secretion]. 1497 81