It is also a short-lived effect because the kidneys become resistant to calcitonin, as demonstrated by the kidneys unaffected excretion of calcium in patients with thyroid tumors that secrete excessive calcitonin.In its skeleton-preserving actions, calcitonin protects against calcium loss from the skeleton during periods of calcium mobilization, such as pregnancy and, especially, lactation. The protective mechanisms include the direct inhibition of bone resorption and the indirect effect through the inhibition of the release of prolactin from the pituitary gland. The reason provided is that prolactin induces the release of PTH related peptide which enhances bone resorption, but is still under investigation.Other effects are in preventing postprandial hypercalcemia resulting from absorption of Ca2+. Also, calcitonin inhibits food intake in rats and monkeys, and may have CNS action involving the regulation of feeding and appetite. Calcitonin lowers blood calcium and phosphorus mainly through its inhibition of osteoclasts. Osteoblasts do not have calcitonin receptors and are therefore not directly affected by calcitonin levels. However, since bone resorption and bone formation are coupled processes, eventually calcitonins inhibition of osteoclastic activity leads to increased osteoblastic activity (as an indirect effect). Receptor
The calcitonin receptor is a G protein-coupled receptor localized to osteoclasts as well kidney and brain cells. It is coupled to a Gsα subunit, thus stimulating cAMP production by adenylate cyclase in target cells. It may also affect the ovaries in women and the testes in men. Discovery
Calcitonin was first purified in 1962 by Douglas Harold Copp and B. Cheney at the University of British Columbia, Canada.
Tiotixene, or thiothixene, sold under the brand name Navane among others, is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania. It was introduced in the United States in 1967 by Pfizer.Tiotixene is also related to thioproperazine and pipotiazine, members of the phenothiazine class. Pharmacology
Pharmacodynamics
Tiotixene acts primarily as a highly potent antagonist of the dopamine D2 and D3 receptors (subnanomolar affinity). It is also an antagonist of the histamine H1, α1-adrenergic, and serotonin 5-HT7 receptors (low nanomolar affinity), as well as of various other receptors to a much lesser extent (lower affinity). It does not have any anticholinergic activity. Antagonism of the D2 receptor is thought to be responsible for the antipsychotic effects of tiotixene. History
Tiotixene was introduced in 1967. Chemistry
Tiotixene is a member of the thioxanthene class of antipsychotics. Analogues include chlorprothixene, clopenthixol, flupentixol, and zuclopenthixol. == References ==