Inhibition of Acetylcholinesterase in Different Structures of the Rat Brain Following Soman Intoxication Pretreated with Huperzine A

Abstract

Acetylcholinesterase (AChE) activities in different brain parts were determined quantitatively in rats treated with huperzine A, soman, and huperzine A followed by soman, using histochemical and biochemical methods. Following soman intoxication (1.2 x LD 50 , i.m.), AChE activity was decreased to 30-80% of control values depending on the brain structure. The most sensitive area was the frontal cortex and the most relatively resistant was ncl. ruber. Huperzine A treatment only caused a change in AChE activity varying from 70 to 100 % of control values. In rats pretreated with huperzine A and intoxicated with soman, AChE activity was significantly higher than that observed after soman. In these animals, survival of rats pretreated with huperzine was observed while the mortality of unpretreated animals was near to 80 %. The results suggest that huperzine A is good candidate for further study for clinical use as a prophylactic drug against nerve agent poisoning.Int. J. Mol. Sci. 2007, 8 1166

Efficient Charge Separation in TiO2 Films Sensitized with Ruthenium(II)–Polypyridyl Complexes: Hole Stabilization by Ligand‐Localized Charge‐Transfer States

“…This should be correlated with its own intrinsic activity, as well as the nature of the OP‐producing intoxication, and the variability of its induced effects at the cerebral AChE level (correlated with specific areas of penetrability and cerebral AChE molecular type). The poor and variable penetration ability of different oximes through the BBB should also be considered (Antonijevic and Stojiljkovic, 2007; Bajgar et al ., 1995, 2007a, b; Bajgar, 2004; Lundy et al ., 2006).…”

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

“…It is worthwhile noting that the minimum reactivation level (approximately 5%) of the phosphorylated AChE by oximes in some of the cerebral areas carrying vital functions -such as the ponto-medullar area -can be essential in OP-poisoned animals' survival rates (Bajgar, 1971(Bajgar, , 1972bBajgar et al, 2007a). However, the minimal AChE recovered activity necessary for survival of rats intoxicated with sarin, soman and VX has been determined to lie in the 5-10% interval (Bajgar et al, 2008).…”

“…This should be correlated with its own intrinsic activity, as well as the nature of the OP-producing intoxication, and the variability of its induced effects at the cerebral AChE level (correlated with specific areas of penetrability and cerebral AChE molecular type). The poor and variable penetration ability of different oximes through the BBB should also be considered (Antonijevic and Stojiljkovic, 2007;Bajgar et al, 1995Bajgar et al, , 2007aBajgar, 2004;Lundy et al, 2006).…”

“…produces a net and rapid antagonism of paraoxon-induced hypothermia (in Table 3. Sequence and toxicodynamic (TD) mechanisms and PD antagonism of OP-induced seizures (Voicu et al, 1974;Shih et al, 2003;Bajgar et al, 2007a;Lundy and Shih, 1983;Raveh et al, 2002Raveh et al, , 2003 Characteristics and duration (Voicu et al, 1974;Raveh et al, 2002Raveh et al, , 2003 (Shih et al, 2007;Carpentier et al, 1994) 3. Third phase: starting 40 min after onset…”

Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

“…Some protective effects against paraoxon were achieved by pretreatment with ranitidine (35) or metoclopramide (21). From other studies of compounds preferably binding to the AChE anionic site, tacrine, 7-methoxytacrine (7-MEOTA) and huperzine A were considered and experimentally studied with respect to prophylaxis against nerve agents in vitro and in vivo (3,6,17,27,33).…”