Activation of Two Different Drugs Used in Alzheimer's Disease Treatment on Human Carbonic Anhydrase Isozymes I and II Activity: an In Vitro Study

Objectives: Human carbonic anhydrase I and II (hCAI, II) isoenzymes were purified from human erythrocyte. Kinetic interactions between the enzymes and memantine and donepezil, two different drugs used in Alzheimer's disease (AD) treatment, were investigated. Materials and Methods: The purification procedure was composed of preparation of homogenate (or hemolysate) and affinity chromatography on Sepharose 4B-L-tyrosine-sulfanilamide. Results: Both drug exhibited in vitro activator effects on hCAI and II enzymes activity. Strong activations were found for these compounds: The CA values of memantine and donepezil against hCAI were 0.013 ?M and 1.8 ?M, respectively. The KA values of memantine and donepezil against hCAII were 0.045 ?M and 3.7 ?M, respectively.Conclusion: Since the levels of CA isoenzymes are low in patients with AD or in the older population, increasing activities of these isoenzymes are important for these patients. The effect of these drugs used in AD treatment was thought to be caused by positive changes in the levels of carbonic anhydrase isoenzymes.