Anti-CHEs

It is the first centrally acting anti-ChE used in mild to moderate cases of AD. Side... 

Dale Pendell riattiva le anti che connessioni tra il poeta bardo e lo sciamano."... 

TABLE 4-3. Anti-ChE Activities of Oral HA, Donepezil, and Tacrine in Rats... 

Figure 4-3. IC50 ( jM) of anti-ChE activities of HA derivatives on AChE (rat erythroc3fte membrane) and BuChE (rat serum) over a concentration range from 1 nM to 10 nM. Data from Refs. 121 and 122.

The major gap in the available information on GA is the lack of either a subchronic or a chronic oral toxicity study from which to derive the RfD. The absence of oral data could be addressed by conducting a subchronic oral toxicity study that assesses anti-ChE activity in red blood cells (RBCs) and plasma in one or preferably two species. If further research reveals that significant toxic effects can be induced by any of the nerve agents at doses below those that cause significant ChE inhibition, additional studies should be conducted to reassess the safety of the recommended RfD for GA. 

ORNL assigned a factor of 10 for the nncertainty factor for the extrapolation of data from animals to humans (UFa) becanse no evidence suggests that humans are less susceptible than rats to GD. ORNL cited the evidence that rodents have much lower RBC-AChE activity than humans (EUin 1981), suggesting that rats might be more susceptible than hnmans to anti-ChE compounds, but also noted that the lower RBC-AChE... 

Many of the physiological effects of anti-ChEs are attributable to excess neurotransmitter ACh (Taylor 1996). The precise symptoms and the time course depend on the chemicals and the localization of the receptors affected. Early symptoms of cholinergic poisoning represent stimulation of muscarinic neuro-effectors of the parasympathetic system. Effects include slowing of the heart (bradycardia), constriction of the pupil of the eye, diarrhea, urination, lacrimation, and salivation. Actions at nicotinic skeletal neuromuscular junctions (motor end plates) result in muscle fasciculation (disorganized twitching) and, at higher doses. 

Although most of the effects of OPs are considered to be due to AChE inhibition, there is evidence that anti-ChEs directly affect ACh receptor channels (Rocha et al. 1996 Katz et al. 1997), that anti-AChE pesticides depress the immune system in experimental animals (Casale et al. 1993), and that choline itself might act as an allosteric regulator of nicotinic receptors in the CNS (Alkondon et al. 1997). 

The toxins that inhibit the AChE are called anticholinesterase (anti-ChE) agents. They cause acetylcholine to accumulate in the vicinity of cholinergic nerve terminals, and thus are potentially capable of producing effects equivalent to excessive stimulation of cholinergic receptors throughout the central and peripheral nervous systems (Long, 1963). Nevertheless, several members of this class of compounds are widely used as therapeutics agents others that cross the blood-brain barrier have been approved or are in clinical trial for the treatment of Alzheimer s disease. 

These aforementioned natural anti-ChE agents can be developed for a different utihty including the extensive application as toxic agents (i.e. potential chemical warfare). 

In rats, the phrenic nerve discharge was prolonged during respiratory depression. Since the toxin F7 has a potent anti-ChE activity, it is concluded that the respiratory failure induced by toxin F7 is peripheral in origin, chiefly, if not entirely, due to its anticholinesterase activity. 

The natural toxins onchidal and fasciculins behave as anti-ChE agents. Onchidal is an active site-directed irreversible inhibitor of AChE, and fasciculins are proteinic AChE inhibitors which bind to a peripheral regulatory anionic site of AChE in a noncompetitive and irreversible manner. 

Thus it can be seen that anti-ChEs are vahd inducers of the cholinergic anti-inflammatory pathway, presumably through their role in increasing ACh levels. 

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