Toxicity anticholinesterases

Benke GM, Cheever KL, Mirer FE, et al. 1974. Comparative toxicity, anticholinesterase action and metabolism of methyl parathion and parathion in sunfish and mice. Toxicol Appl Pharmacol 28 97-109. 

Toxieology. Parathion is a highly toxic anticholinesterase agent. 

Nerve agents are toxic anticholinesterase compounds by all routes of exposure, and exhibit a steep dose-response. Detailed descriptions of nerve agent toxicity may be found in reviews by Bakshi et al (2000), NRC (1999, 2003), Mioduszewski et al (1998), Marts (2007), Opresko et al (1998), Sidell (1997), Somani and Husain (2001), Munro et al. (1994), and others. 

Tetraethyl pyrophosphate. Very toxic anticholinesterase originally synthesized as a potential insecticide. Lethal dose oral 1.1 mg/kg, dermal 2.4 mg/kg. 

Gupta, R. C. (1995). Rnvirooincnial agents and placental toxicity Anticholinesterases and other agents. In Placental Toxicology (B. V. R. Sastry. Ed.), pp. 257-278. CRC Press. Boca Raton, FL. 

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Galal EE, Samaan HA, Nour El Dien S, et al. 1977. Studies on the acute and subchronic toxicities of some commonly used anticholinesterase insecticides in rats. J Drug Res Eg t 1-17. 

Grob D, Garlick WL, Harvey AM. 1950. The toxic effects in man of the anticholinesterase insecticide parathion (p-nitrophenyl diethylthionophosphate). Johns Hopkins Med J 87 106-129. 

Rider JA, Moeller HC, Puletti EJ. 1966. Continuing studies on anticholinesterase effect of methyl parathion in humans and determination of level of incipient toxicity of OMPA [Abstract]. Fed Proc 25 687. 

Rider JA, Swader Jl, Puletti EJ. 1971. Anticholinesterase toxicity studies with methyl parathion, guthion, and phosdrin in human subjects [Abstract]. Fed Proc 30 443. 

The carbamate and OP insecticides and the organophosphorous nerve gases soman, sarin, and tabun all act as anticholinesterases, and most of their toxicity is attributed to this property. The naturally occurring carbamate physostigmine, which has been used in medicine, is also an anticholinesterase. Some OP compounds can cause relatively long-lasting inhibition of the enzyme because of the phenomenon of... 

Other mnch more toxic componnds operating throngh specific biochemical mechanisms (e.g., OP anticholinesterases) cannot be modeled in this way. If... 

ACh is metabolised extraneuronally by the enzyme acetylcholinesterase, to reform precursor choline and acetate. Blocking its activity with various anticholinesterases has been widely investigated and some improvement in memory noted. Such studies have invariably used reversible inhibition because of the toxicity associated with long-term irreversible inhibition of the enzyme. Physostigmine was the pilot drug. It is known to improve memory in animals and some small effects have been seen in humans (reduces number of mistakes in word-recall tests rather than number of words recalled), but it really needs to be given intravenously and has a very short half-life (30 min). 

GB is a lethal anticholinesterase agent. Its toxic hazard is high for inhalation, ingestion, and eye/skin exposure. Due to its high volatility, it is mainly an... 

The toxic organic phosphorus compounds act as powerful inhibitors of cholinesterase, an enzyme found predominantly in the nervous tissue of animals, including insects. This enzyme hydrolyzes acetylcholine, which plays an essential role in the transmission of nerve impulses. The toxicity of compounds in this series can be largely accounted for on the basis of their anticholinesterase activity (7,8,12,14, SI). 

Toxification rates may vary. For example, when humans are acutely poisoned by the systemic insecticide menazon, there is an incubation period (of up to one day) and a slow growth in the anticholinesterase activity when the PS-form with low toxicity becomes the active PO-form [A17]. 

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