PPIs interference in Ach biosynthesis in degenerative dementia

It has long been known that a decline in cognition in patients with neurodegenerative syndromes (like dementia) are symptomatically associated with decreased acetylcholine uptake, postsynaptically.

Widespread use of certain classes of medications have been associated with this phenotype—NSAIDS, aluminum compounds, etc.


[F]or the first time compelling evidence that PPIs reversibly inhibit the activity of the core‐cholinergic enzyme ChAT, with unprecedented selectivity and potencies that lie far below their in vivo plasma and CSF concentration in humans even at lowest dosages used by millions of people worldwide. This unexpected mode of action together with pharmacoepidemiological observation warrant further mechanistic studies on PPIs in relation to dysfunction of the cholinergic system.

Interesting, but heavy, read.

Michael L. Douglas @doctorpundit

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