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Antimalarials inhibit human erythrocyte membrane acetylcholinesterase
Subhash D Katewa1, Surendra S Katyare
1Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India. subhash-katewa@uiowa.edu
Drug and Chemical Toxicology
|November 22, 2005
Summary
Chloroquine (CQ) and other antimalarials inhibit human acetylcholinesterase (AChE). CQ is the most potent inhibitor, suggesting potential neuroprotective uses against Alzheimer's disease.
Area of Science:
- Biochemistry
- Pharmacology
- Neuroscience
Background:
- Acetylcholinesterase (AChE) is a key enzyme in neurotransmission.
- Antimalarials are known to have diverse biological activities.
Purpose of the Study:
- To investigate the inhibitory effects of chloroquine (CQ), primaquine (PQ), and quinine (Q) on human erythrocyte membrane AChE.
- To elucidate the mechanisms of AChE inhibition by these antimalarials.
Main Methods:
- Enzyme kinetics assays were performed to determine inhibition constants (K(i)) and Michaelis-Menten parameters (K(m), V(max)).
- Hill plot analysis was used to characterize the binding kinetics of CQ.
Main Results:
- Chloroquine (CQ) demonstrated the most potent inhibition of AChE, followed by primaquine (PQ) and quinine (Q).
- All three antimalarials exhibited mixed-type inhibition, decreasing V(max) and increasing K(m) of AChE.
- CQ showed complex binding kinetics with de-binding observed at higher concentrations.
Conclusions:
- Antimalarials, particularly 4-aminoquinoline derivatives like CQ, are potent inhibitors of AChE.
- Their dual action as anti-inflammatory agents and cholinesterase inhibitors suggests potential therapeutic applications as neuroprotective agents in Alzheimer's disease.
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