Acta Med. 2005, 48: 145-148

In vitro Inactivation of Rat Brain Acetylcholinesterase by DSP-4 and Its Derivatives OS-21 and OS-23 and Protective Activity of Tacrine (9-Amino-1,2,3,4-tetrahydroacridine)

Jiří Patočkaa,b, Daniel Junb,c, Kamil Kučab

aSouth Bohemia University, Faculty of Health and Social Studies, Department of Radiology and Toxicology, Czech Republic
bUniversity of Defence, Faculty of Military Health Sciences, Department of Toxicology, Czech Republic
cCharles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, Czech Republic

Received November 1, 2004
Accepted June 1, 2005

Tertiary N-haloethylamines are able to cyclize to the corresponding aziridinium ions. The inhibitory activity of the DSP-4 (N-(o-brombenzyl)-N-ethyl-2-chlorethylamine) and its two derivatives OS-21 (N-benzyl-N-ethyl-2-chloroethylamine) and OS-23 (N-fenylethyl-N-ethyl-2-chloroethylamine) was studied toward rat brain acetylcholinesterase (AChE) in vitro. The influence of the THA (tacrine; 9–amino-1,2,3,4–tetrahydroacridine) on AChE inhibition by these substances was also evaluated. The results demonstrated that all of three aziridinium compounds formed in solution caused a timeand concentration-dependent irreversible enzyme inhibition. The association of aziridinium compounds with the AChE was a relatively slow second-order reaction. DSP-4 showed the fastest rate of AChE alkylation, OS-21 had a lowered rate and OS-23 displayed the lowest rate. Pretreatment of the enzyme by THA decreased the rate of alkylation by all three aziridinium compounds by allosteric mechanism.


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