Methylacridinium and its cholinergic properties
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Acetylcholinesterase chemistry pharmacology MeSH
- Acridines chemistry MeSH
- Butyrylcholinesterase blood chemistry pharmacology MeSH
- Models, Chemical * MeSH
- Cholinergic Agents pharmacology MeSH
- Blood-Brain Barrier drug effects physiology MeSH
- Inhibitory Concentration 50 MeSH
- Rats MeSH
- Humans MeSH
- Urinary Bladder drug effects metabolism MeSH
- Mice MeSH
- Computer Simulation MeSH
- Rats, Sprague-Dawley MeSH
- Swine MeSH
- Regression Analysis MeSH
- Serum metabolism MeSH
- Heart drug effects MeSH
- Substrate Specificity MeSH
- Protein Binding drug effects MeSH
- Binding Sites drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Acridines MeSH
- Butyrylcholinesterase MeSH
- Cholinergic Agents MeSH
- N-methylacridine MeSH Browser
10-Methylacridinium iodide (methylacridinium; MA) is an inhibitor of cholinesterases. Inhibitors of acetylcholinesterase (AChE) are used in the treatment of myasthenia gravis, Alzheimer's disease, and in the prophylaxis of poisoning with organophosphates. Using spectrophotometric Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50) = 1.68 +/- 0.14 1M; human recombinant AChE) and equally to its inhibition of butyrylcholinesterase (BuChE; IC(50) = 3.54 +/- 0.27 1M; BuChE from human serum). MA also inhibits the binding of [(3)H]N-methylscopolamine to the muscarinic M2 receptor subtype, possibly in an allosteric manner (IC(50) = 1.90 1M). Functional effects on both the enzyme and the receptor could be observed in contractile studies on the isolated rat bladder. The ability of MA to cross the blood-brain barrier (log P = -0.32; polar surface area 3.88) provides prerequisites for a potential use of the drug in the treatment of neural disorders.
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