In vitro effects of acetylcholinesterase reactivators on monoamine oxidase activity

作者: Zdeněk Fišar , Jana Hroudová , Jan Korábečný , Kamil Musílek , Kamil Kuča

DOI: 10.1016/J.TOXLET.2010.12.023

关键词:

摘要: Abstract Administration of acetylcholinesterase (AChE) reactivators (oximes) is usually used in order to counteract the poisoning effects nerve agents. The possibility was suggested that oximes may show some therapeutic and/or adverse through their action central nervous system. There are no sufficient data about interaction with monoaminergic neurotransmitter's systems brain. Oxime-type AChE pralidoxime, obidoxime, trimedoxime, methoxime and HI-6 were tested for potential affect activity monoamine oxidase type A (MAO-A) B (MAO-B) crude mitochondrial fraction pig brains. compounds found inhibit fully MAO-A half maximal inhibitory concentration (IC50) 0.375 mmol/l (pralidoxime), 1.53 mmol/l (HI-6), 2.31 mmol/l (methoxime), 2.42 mmol/l (obidoxime) 4.98 mmol/l (trimedoxime). Activity MAO-B inhibited by pralidoxime only IC50 4.81 mmol/l 11.01 mmol/l, respectively. Methoxime, obidoxime trimedoxime displayed non-monotonic dependent effect on activity. Because concentrations effective MAO inhibition could not be achieved vivo at cerebral level, we suppose investigated do interfere brain therapeutically relevant concentrations.

参考文章(44)
Osamu Suzuki, Hiroshi Seno, Takeshi Kumazawa, inhibition of human platelet monoamine oxidase by phenothiazine derivatives Life Sciences. ,vol. 42, pp. 2131- 2136 ,(1988) , 10.1016/0024-3205(88)90127-0
Jana Hroudová, Jirí Raboch, Zdenek Fisar, Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers. Neuro endocrinology letters. ,vol. 31, pp. 645- 656 ,(2010)
Sven Ove Ögren, Therese M. Eriksson, Elin Elvander-Tottie, Claudio D’Addario, Joanna C. Ekström, Per Svenningsson, Björn Meister, Jan Kehr, Oliver Stiedl, The role of 5-HT(1A) receptors in learning and memory. Behavioural Brain Research. ,vol. 195, pp. 54- 77 ,(2008) , 10.1016/J.BBR.2008.02.023
Moussa B H Youdim, Y S Bakhle, Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness. British Journal of Pharmacology. ,vol. 147, ,(2006) , 10.1038/SJ.BJP.0706464
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
Stephen M. Stahl, Angela Felker, Monoamine Oxidase Inhibitors: A Modern Guide to an Unrequited Class of Antidepressants Cns Spectrums. ,vol. 13, pp. 855- 871 ,(2008) , 10.1017/S1092852900016965
H. P. M. van Helden, Ruud W. Busker, Bert P. C. Melchers, Piet L. B. Bruijnzeel, Pharmacological effects of oximes: how relevant are they? Archives of Toxicology. ,vol. 70, pp. 779- 786 ,(1996) , 10.1007/S002040050340
Peter Eyer, Franz Worek, Horst Thiermann, Michael Eddleston, Paradox findings may challenge orthodox reasoning in acute organophosphate poisoning Chemico-Biological Interactions. ,vol. 187, pp. 270- 278 ,(2010) , 10.1016/J.CBI.2009.10.014
Koichi Sakurada, Hiroshi Ikegaya, Hikoto Ohta, Hisayo Fukushima, Tomoko Akutsu, Ken Watanabe, Effects of oximes on mitochondrial oxidase activity Toxicology Letters. ,vol. 189, pp. 110- 114 ,(2009) , 10.1016/J.TOXLET.2009.05.007
Tsung-Ming Shih, Jacob W. Skovira, John C. O’Donnell, John H. McDonough, Evaluation of nine oximes on in vivo reactivation of blood, brain, and tissue cholinesterase activity inhibited by organophosphorus nerve agents at lethal dose. Toxicology Mechanisms and Methods. ,vol. 19, pp. 386- 400 ,(2009) , 10.1080/15376510903213892