Nerve agents clinical effects

Receptor-mediated endocytosis may be possible because receptors have a high affinity for BDNF (Deckner et al. 1993). A linear relation between intranasal administration of -labeled NGF and brain concentrations of the compound suggest that this transportation is not mediated by receptors and that this releasing method of agents to the brain via olfactory nerves may be effective for many therapies (Frey et al. 1995). BDNF and the insulin-type growth factor (IGF-1) are currently used in clinical studies (Appel 1997). 

Among promising candidates as antidotes against CNS intoxication by OP nerve agents, memantine (MEM) has been shown to pose both anti-excitotoxic and anti-epileptic properties. Memantine is an uncompetitive NMDA receptor antagonist, clinically used for the treatment of Alzheimer s disease, Parkinson s disease and spasticity, in the absence of serious side effects (Ozsuer et al, 2005 Lipton, 2005). From a series of rat in vivo experiments, it is evident that pre-administration of memantine significantly protects... 

Nerve agents are organic esters of phosphorus-based acid derivatives that are potent inhibitors of AChE. A large toxicological and medical literature has been produced since their development, and it has been helpfrd to classify exposure-associated health effects in terms of four general clinical classifications that have been described elsewhere in the literature (Brown and Brix, 1998), and are summarized as 1 through 4 below. To these, I have added a fifth, for which I have finally presented a brief rationale below, and will deal with in more detail subsequently. These are ... 

Liquid nerve agents applied dermally cause local sweating and muscular twitching starting 3 min to 2 h after exposure. Signs last for 3 to 5 days. Following dermal exposure to a large drop clinical effects start within 30 min but with small drops a delay of up to 18 h can be seen (Sidell et al, 1997). 

Following nerve agent exposure, inhibition of the tissue enzyme blocks its ability to hydrolyze the neurotransmitter acetylcholine at the cholinergic receptor sites. Thus, acetylcholine accumulates and continues to stimulate the affected organ. The clinical effects of nerve agent exposure are caused by excess acetylcholine. 

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