Acetylcholinesterase inhibition spontaneous

Stojiljkovic, M.P., Pantelic, D., Maksimovic, M. (2001). Tabun, sarin, soman and VX poisoning in rats kinetics of inhibition of central and peripheral acetylcholinesterase, ageing, spontaneous and oxime-facilitated reactivation. Vll International Symposium on Protection against Chemical and Biological Agents. Stockholm, Sweden, June 15-19,... 

H45. Hovanec, J. W., and Lieske, C. N., Spontaneous reactivation of acetylcholinesterase inhibited with para-substituted phenyl methylphosphonochloridates. Biochemistry 11, 1051-1056 (1972). 

Carbamate poisoning produces reversible acetylcholinesterase inhibition, and spontaneous recovery of enzyme activity may occur within several hours, making these tests less usehl. 

Dewair M, Baur X, Mauermayer R. 1983. Inhibition of acetylcholinesterase by diisocyanates and its spontaneous reactivation. Int Arch Occup Environ Health 52 257-261. 

In recent studies, it was shown that eel acetylcholinesterase (AChE, EC 3.1.1.7) previously inhibited with 1,3,2-dioxaphosphor-inane 2-oxides (I) undergoes spontaneous reactivation with tj, =... 

Carbamates also include pesticides such as Sevin, aldicarb, and carbaryl. They are more degradable than organophosphates and have lower dermal toxicides. Their toxicity is also due to inhibition of acetylcholinesterase but they do not penetrate the central nervous system, so most effects are respiratory in nature. An acetylcholinesterase, which has been carbamylated can undergo spontaneous hydrolysis in vivo, which reactivates the enzyme leading to less severe symptoms or a shorter duration of symptoms. Carbaryl has a low toxicity for mammals however, Perimicarb is highly toxic to mammals, but not readily absorbed through the skin. 

These compounds inhibit the hydrolysis of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase within the mammalian nervous system (Zwiener and Ginsburg, 1988). This inhibition causes acetylcholine levels to rise, thus causing cholinergic hyperstimulation at muscarinic and nicotinic receptors. There are important differences in the way carbamates and OPs bind to acetylcholinesterase as well as their abililty to affect the CNS. Carbamates are reversible inhibitors of cholinesterase enzymes. Carbamates create a reversible bond to the cholinesterase enzyme through carbamylation which can spontaneously hydrolyze, reversing toxicity. Carbamate poisoning produces toxicity similar to that of OPs however, the toxicity is usually of a shorter duration and less severe in nature (Lifshitz et al, 1994). In contrast, OPs inhibit cholinesterase via an irreversible bond of phosphate radicals... 

Mason, H.J., Sams, C., Stevenson, A.J., Rawbome, R. (2000). Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organo-phosphorus pesticides. Plum. Exp. Toxicol. 19 511-16. 

This compound inactivates acetylcholinesterase by formation of "an unstable covalent intermediate." The inhibited enzyme hydrolyzes spontaneously with 1/2 10 min. Com-... 

Tabun-inhibited enzyme (an O-ethyl N,N-dimethylamidophosphoro derivative) is slow to reactivate and Heilbronn (1963) found no detectable spontaneous reactivation with human acetylcholinesterase. The reasons for this are becoming more clear. Tabun binding of mouse acetylcholinesterase causes conformational changes in the enzyme that may stabilize the enzyme-inhibitor complex even without ageing of the complex (Ekstrom et al., 2006). 

One of the clinical signs associated with MeHg intoxication is a myasthenia gravis-like muscle weakness in adults (Rustam et al. 1975), a syndrome which responded well to therapy with neostigmine, a reversible acetylcholinesterase inhibitor. In this syndrome, two effects of MeHg on synaptic transmission at the neuromuscular junction were demonstrated using intracellular microelectrode recording techniques (Atchison and Narahashi 1982 Atchison et al. 1984). First, nerve-evoked, synchronous quantal release of acetylcholine (ACh) is inhibited, as indicated by a decrease in end-plate potential (EPP) amplitude. Second, spontaneous quantal release... 

In insects poisoned by organic phosphorus compounds, assays for acetylcholinesterase show that this enzyme becomes increasingly inhibited dvuring the first hour and the levels of free acetylcholine rise sharply (Small-man and Fisher, 1958). This rise causes a great increase in spontaneous nerve activity (neuronal hyperexcitation), both autonomic and somatic. This state brings about liberation of tissue toxins, ion imbalance, with eventual paralysis, dehydration, and death this sequence is reminiscent of that caused by the chlorinated insecticides (see Section 7.6c for this comparison and for general information on biochemistry of the insect nervous system). 

---