uptake by the thyroid gland; but they have severe side effects. In recent years, the drugs
of choice for controlling hyperthyroidism are thioamides such as 6-propylthiouracil
(5.110) and methimazole (5.111), both of which are cyclic derivatives of thiourea,
inhibiting the thyroid peroxidase that is essential to iodine organification during biosyn-
thesis of the thyroid hormones. In some countries, carbimazole (5.112), which is meta-
bolically converted to methimazole in vivo,is also used. Structure–activity studies of
these orally active antithyroid agents reveal that the thiocarbamide group (-N-C(=S)-R)
is essential for their antithyroid activity.
5.19.2 CalcitoninCalcitonin (CT) is a peptide containing 32 amino acids. Calcitonin obtained from dif-
ferent species is essentially identical over the first nine residues, as well as containing
a glycine at position 28 and a C-terminal prolylamide; this prolylamide, as well as a
disulphide linkage between residues 1 and 7, is crucial for bioactivity. Residues 10–27
can be varied to influence the potency and half-life of the resulting peptide analog.
Calcitonin isolated from fish exhibits potency about 20–25 times higher than that of
mammalian CT because of its higher receptor affinity in bone and kidney. Calcitonin
decreases the Ca^2 +content of plasma by increasing Ca^2 +and PO 42 −excretion in the urine,
as well as inhibiting the absorption of these ions in the intestine. It also decreases the
activation (hydroxylation) of vitamin D, another regulator of Ca^2 +and phosphorus
metabolism. In addition, CT prevents the mobilization of Ca^2 +from bone. CT has been
used to treat postmenopausal osteoporosis and the hypercalcemia that accompanies
malignancies such as metastatic breast carcinoma or multiple myeloma. Salmon calci-
tonin (Miacalcin) is available in a nasal spray formulation.
5.19.3 ParathyrinParathyrin (parathyroid hormone, parathormone, PTH) is secreted by the parathyroid
glands. A peptide of 84 amino acids, it has two precursors during its biosynthesis, a
HORMONES AND THEIR RECEPTORS 363