active site. APAs provide faster inhibition than PPIs since they do not require acid activation. Revaprazan was the first APA used clinically in east Asia, and other APAs are being developed since they appear to provide better acid control in clinical trials. Inactivation of the proton pump can also lead to health problems. A study in mice by Krieg et al. found that a mutation of the pump’s α-subunit led to achlorhydria, resulting in problems with iron absorption, leading to iron deficiency and anemia. The use of PPIs has not been correlated with an elevated risk of anemia, so the H+/K+-ATPase is thought to aid iron absorption but is not necessarily required. Current association of dementia and PPIs have been documented in Germany and in research articles denoting how Benzimidazole derivatives, Astemizole (AST) and Lansoprazole (LNS) interact with anomalous aggregates of tau protein (neurofibrillary tangles). Current theories include the non-selective blockade of sodium-potassium pumps in the brain causing osmotic imbalances or swelling in the cells. [auth opinion] Interaction of PPIs with other drug affecting the sodium-potassium pump, e.g., digoxin, warfarin etc., has been well documented. Memory has been associated with astrocytes and the alpha3 subunit of adenosine receptor found in hydrogen/Sodium-potassium pumps may be a focal point in dementia. Chronic use of PPIs may cause down regulation of alpha3 subunit increasing damage to astrocytes. Osteopetrosis via TCIRG1 gene has a strong association with pre-senile dementia. See also Discovery and development of proton pump inhibitors Solvated electron References External links Body fluids Digestive system Hydrogen biology Transport proteins EC 3.6.3