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.
- MeSH
- acetylcholinesterasa farmakologie chemie MeSH
- akridiny chemie MeSH
- butyrylcholinesterasa farmakologie chemie krev MeSH
- chemické modely MeSH
- cholinergní látky farmakologie MeSH
- hematoencefalická bariéra fyziologie účinky léků MeSH
- inhibiční koncentrace 50 MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- močový měchýř metabolismus účinky léků MeSH
- myši MeSH
- počítačová simulace MeSH
- potkani Sprague-Dawley MeSH
- prasata MeSH
- regresní analýza MeSH
- sérum metabolismus MeSH
- srdce účinky léků MeSH
- substrátová specifita MeSH
- vazba proteinů účinky léků MeSH
- vazebná místa účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
