Central nervous system AChE inhibition, effects

Nerve agents are OP compounds, which irreversibly inhibit AChE, leading to ACh accumulation, and cause over-stimulation of muscarinic and nicotinic ACh receptors. The effect at the SA node, the primary heart control site, is inhibitory and bradycardia results. VX primarily affects neurotransmitter receptors, those of norepinephrine, and also affects the central nervous system (CNS) not related to AChE inhibition. 

The effect of dichlorvos exposure on lipid peroxidation and the antioxidant defense system in different regions of the rat central nervous system was also studied. Inhibition of AChE activity was used as an index of dichlorvos... 

Evidence indicates that OPs can induce chronic effects on both the peripheral and central nervous systems following acute intoxication (Jamal, 1997). The mechanisms for this condition are not related to the inhibition of AChE or NTE. Two types of such disorders have been documented type I, representing COPIND following an acute poisoning episode(s), and type II, representing COPIND following a chronic long-term exposure to subclinical doses. There is no distinction in the chemical nature of OPs for their apparent ability to cause COPIND. 

The crucial question dealing with the reactivator s effect on the central nervous system was discussed in the past. Because of their quaternary structure, at intact BBB, the penetration of the reactivators is slow. In order to reach an effective concentration of the reactivator in CNS, its extremely high plasma concentration is necessary. On the other hand, some authors (E3, FI, H12) have suggested that the central reactivation effect exists. It is known from other results that the inhibition and reactivation of AChE in the brain is selective for different OP (B6, B7, B33) and following administration of the reactivators to nerve agent-intoxicated animals, reactivation of AChE in different parts of the brain was demonstrated (B19, B20, B24). The ability of oximes to penetrate the blood-brain barrier was confirmed by Sakurada et al. (SI). 

The acute effects of OPs are usually due to their Inhibition of AChE at the motor end plates of the peripheral and the synapses of the central nervous systems. Unfortunately, OPIDN Is not related In any simple way to these Inhibitions. 

Research into linalool-rich plants from Brazil demonstrates potent effects on the central nervous system in vivo, including sedative, spasmolytic and hypothermic activity. Linalool has been shown to modulate glutamate activation expression in vivo and in vitro and may also inhibit GABAergic transmission (Elizabetsky et al. 1999). Linalool has also been shown to produce an inhibitory effect on acetylcholine (Ach) release and on the channel opening time of the neuromuscular junction, as well as a local anaesthetic action (Re et al. 2000). 

The OPs exert their main toxicological effects by non-reversible phosphorylation of esterases in the central nervous system, whereas the acute toxic effects are related to inhibition of acetylcholinesterase (AChE) (Sogorb and Vilanova 2002). AChE is a very efficient enzyme, since one unique molecule hydrolyses approximately 5,000 acetylcholine (ACh) molecules per second (Schofield and Dinovo 2010). ACh is a chemical mediator, needed for transmission of nerve impulses, present in mammals and insects (Santos et al. 2007). 

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