The drug to relieve stomach acid has side effects on the nerves of the brain?

REVIEW: The latest study found that long-term use PPIs, can be suppressed by efficient selection ChAT activity, increase the risk of dementia, and the restraining force of omeprazole strongestOF: Wang Xuan a proton pump inhibitor (PPI) for the treatment of hyperacidity (e.g., peptic ulcer and gastroesophageal reflux) is the most common one of the drugs and non-prescription drugs as the purchaser taking a lot of common clinical omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole and so oncholinergic neurons projecting system throughout the body, to control the various organs, muscles and glands autonomic function, which can be detected by the cell of acetylcholine (of ACh) biosynthetic enzyme, choline acetyltransferase ( to identify ChAT) existsPrevious studies showed that a number of neurodegenerative diseases, such as defining characteristic of dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and Down syndrome (DS) common to Alzheimer's disease (AD) of one is that cholinergic neurons degenerate networkepidemiological studies have pointed out that many drugs, long-term and cumulative exposure has anticholinergic effects of the drug will not only produce clinical symptoms similar to dementia, and in fact will increase the incidence of dementiaEpidemiological studies have also found that PPIs significantly increase the risk of dementia, but the underlying mechanism remains unclearRecently, researchers from Sweden's Karolinska Institute on "Alzheimer's & Dementia" published the latest research this issue and found that long-term use PPIs, can inhibit the activity of ChAT by efficient selection, increased dementia suppression force of risk, and omeprazole strongestDOI: 10.1002 / alz.12113researchers first found by computational screening all the PPI (omeprazole, lansoprazole, pantoprazole, rabeprazole, for Na Tuola oxazole and ilaprazole) can be used as a potential ligand ChAT personDocking analyzed six further determined ChAT PPI can interact with the molecule and then using a computerA a in vitro screening inhibitors since ChAT is acetyl coenzyme A for ACh ChAT required for the biosynthesis of cofactors, researchers to choline and acetyl coenzyme A as a substrate to test most commonly omeprazole , lansoprazole and pantoprazole% inhibition, i.eIC50 values, the results were 0.1,1.5 and 5.3μMThis indicates that three kinds of PPI could significantly inhibit ChAT, and the inhibition rate of omeprazole and pantoprazole Bilansuola azole of from about 15 to 50 times strongerConsidering the IC 50 values ​​will vary with the concentration of the enzyme substrate, the researchers using an enzyme kinetic analysis system to determine the inhibition PPI inhibition constant (Ki) and the inhibition of ChAT embodimentIt was found that omeprazole Ki ranging between 70 and 140 nM, its performance for mixed-competitive reversible inhibitors of ChAT, i.eomeprazole will be binding with high affinity choline enzyme in terms of concentration, with the regardless of the state of the enzyme (i.e., free or substrate binding choline)In addition, it was found for inhibition of Na Tuola and rabeprazole higher efficacy than ChAT omeprazole, are expressed as noncompetitive inhibitor of ChAT, i.e the free enzyme and its choline bound enzymes have the same high affinity, regardless of the concentration of substrate in vivo choline, they can be suppressed ChAT a choline as substrate PPI enzyme inhibition kinetic analysis of acetyl coenzyme A to a PPI inhibiting the enzyme substrate kinetic analysis PPIs mode of action as inhibitors of ChAT < br /> researchers tested PPIs known potent inhibitor of ChAT Related tags: a Sweden, a proton pump inhibitor, drug side effects < br /> 0 0