In vitro effects of acetylcholinesterase reactivators on monoamine oxidase activity |
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Authors: | Fi?ar Zdeněk Hroudová Jana Korábe?ný Jan Musílek Kamil Ku?a Kamil |
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Institution: | a Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic b Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic c Department of Toxicology, Faculty of Military Health Sciences, University of Defence, T?ebešská 1575, 500 01 Hradec Králové, Czech Republic d Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, T?ebešská 1575, 500 01 Hradec Králové, Czech Republic e University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic |
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Abstract: | Administration of acetylcholinesterase (AChE) reactivators (oximes) is usually used in order to counteract the poisoning effects of nerve agents. The possibility was suggested that oximes may show some therapeutic and/or adverse effects through their action in central nervous system. There are no sufficient data about interaction of oximes with monoaminergic neurotransmitter's systems in the brain. Oxime-type AChE reactivators pralidoxime, obidoxime, trimedoxime, methoxime and HI-6 were tested for their potential to affect the activity of monoamine oxidase of type A (MAO-A) and type B (MAO-B) in crude mitochondrial fraction of pig brains. The compounds were found to inhibit fully MAO-A with half maximal inhibitory concentration (IC50) of 0.375 mmol/l (pralidoxime), 1.53 mmol/l (HI-6), 2.31 mmol/l (methoxime), 2.42 mmol/l (obidoxime) and 4.98 mmol/l (trimedoxime). Activity of MAO-B was fully inhibited by HI-6 and pralidoxime only with IC50 4.81 mmol/l and 11.01 mmol/l, respectively. Methoxime, obidoxime and trimedoxime displayed non-monotonic concentration dependent effect on MAO-B activity. Because oximes concentrations effective for MAO inhibition could not be achieved in vivo at the cerebral level, we suppose that oximes investigated do not interfere with brain MAO at therapeutically relevant concentrations. |
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Keywords: | AChE acetylcholinesterase MAO monoamine oxidase IC50 half maximal inhibitory concentration CNS central nervous system PEA 2-phenylethylamine |
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