Calcium mimetic

Teva has patented two routes towards Cinacalcet hydrochloride 23, a calcium mimetic that helps regulate calcium levels in the treatment of bone disease, based on the Heck reactirMi (Scheme 7). In both routes /n-bromo-trifluorotoluene 20 was... 

The calcium channel blockers have been associated with both prolonged pregnancy and decreased neonatal morbidity.36,42 when compared with P-mimetics (e.g., terbutaline) and magnesium, they show better neonatal outcome and a lower incidence of serious maternal side effects.42 Potential minor maternal adverse effects include headache, flushing, dizziness, and transient hypotension.41... 

Once the hypercalcemic crisis has resolved, or in patients with milder calcium elevations, longterm therapy can be initiated. Parathyroidectomy remains the definitive therapy for primary hyperparathyroidism. As described below, a Ca mimetic that stimulates the CaSR is a promising therapy for hyperparathyroidism. If the hypercalcemia results from malignancy, therapy ideally is directed at the underlying cancer. When this is not possible, intermittent dosing of parenteral bisphosphonates has been used to keep serum Ca within an acceptable range. 

In the case of peroxovanadate (which may be formed in situ), vanadate plus superoxide radicals, or vanadate with added hydrogen peroxide, the mechanism appears to be increased autophosphorylation and activation of the insulin receptor, with consequent stimulation of glucose uptake. However, effects of intracellular vanadium on calcium influx as well as intracellular and intravesicular pH modification have not been ruled out as important factors in the mechanism of action of vanadium as an insulin-mimetic agent. 

Arachidonic acid, TXA2, PGH2 and their stable mimetics produce an increase in intracellular free calcium in human platelets or alter the binding or flux of calcium in platelet membrane vesicles " ". These effects were blocked by the receptor antagonist, 13-azaprostanoic acid ". The dense tubular system is believed to be the source of calcium. The mechanism by which calcium is elevated in platelets by TXA2/PGH2 or their mimetics remains unknown. However, much recent evidence suggests that turnover of phophatidyl inositol polyphosphates plays an important intermediary role ". ... 

Researchers have studied whether acyl-chain order could be responsible for the preferred sterol interaction with SMs. Acyl-chain order was deduced from diphenylhexatriene anisotropy and from the deuterium order parameter obtained by H-NMR on bilayers made from either 14 0/14 0(d27)-PC, or 14 0(d27)-SM7 Some researcher analyzed the ground and excited states of phospholamban (PLN), a membrane protein that regulates sarcoplasmic reticulum (SR) calcium ATPase (SERCA), in dilferent membrane mimetic environments. Gustavsson et al. have previously proposed that the conformational equilibrium of PLN are central to SERCA regulation. They have now shown that these equilibrium detected in micelles and bicelles are also present in native sarcoplasmic reticulum lipid membranes as probed by MAS solid-state NMR. ... 

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