Insecticides carbamates/cholinesterase inhibitors

The carbamates, like the organophosphorus insecticides, are cholinesterase inhibitors. However, the reaction is rapidly reversible. Carbaryl has a half life in the soil of about 8 days and is decomposed by ultraviolet light. The carbamates metabolize rapidly in animals and show little, if any, propensity for storage in animal tissues. Additional properties and reactions of carbamates are discussed in the section on fungicides. 

Cholinesterase inhibitor (anti-cholinesterase, ChEI) is a chemical that prevents cholinesterases (ChEs) from breaking down. ACh, which consequently increases the level and duration of action of this neurotransmitter. ChEIs such as organophosphates (esters of phosphoric acid) and carbamates (esters of carbamic acid) - serve as insecticides, pesticides, warfare agents and drugs. 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

Two important classes of cholinesterase inhibitors are the organophosphates and the carbamates, a few of which are widely used insecticides. Two such insecticides are chloropyrifos and carbaryl (structures shown). They are highly effective insecticides and, if used properly, appear to be without significant risk to humans (although the use of chloropyrifos and some other members of the class is somewhat controversial). 

Insecticides fall largely into three main chemical groups 1) the organochlorines whose action is primarily on the peripheral nervous system 2) organophosphates, and 3) carbamates. The latter two classes are cholinesterase inhibitors. 

Carbamate anticholinesterases these are reversible in as much as their duration of action is short as compared to organophosphorus anticholinesterases, and are used extensively. An example is carbaryl (carbaril) and several analogues of carbaryl are used as insecticides. However, not all carbamates found in garden formulations are cholinesterase inhibitors the dithiocarbamates are fungicidal. 

Agents that cause these symptoms include organo-phosphate and carbamate insecticides (cholinesterase inhibitors),pilocarpine, physostigmine, and certain species of mushrooms that contain muscarine. 

Use of NLO likely improves response and reduces systemic adverse effects and should be performed by all patients administering cholinesterase inhibitors. These agents should be used with caution in patients with asthma, retinal detachments, narrow angles, bradycardia, hypotension, heart failure, Down s syndrome, epilepsy, parkinsonism, peptic ulcer, and ocular inflammation, as well as in those receiving cholinesterase inhibitor therapy for myasthenia gravis or exposure to carbamate or organophosphate insecticides and pesticides. ... 

The term pesticide includes chemicals used to eradicate rodents (rodenticides), fungi (fungicides), weeds (herbicides) and insects (insecticides). These agrochemicals may be used directly on the medicinal plant crop itself, they may be used on crops growing adjacent to the herbs or they may occur as general environmental pollutants in soil, air or water. The presence of insecticide residues is of particular concern because those of the organochlorine type (DDT etc.) have been shown to cause cancers in animals and those of the organophosphate and carbamate types are potent cholinesterase inhibitors. 

C. Cholinesterase Inhibitors The carbamates (eg, aldicarb, carbaryl) and organophosphates (eg, dichlorvos, malathion, parathion) are effective insecticides with short environmental half-lives. The cholinesterase inhibitors are inexpensive and are heavily used in agriculture. 

Moderately toxic herbicide exhibited low to moderate toxicity in experimental animals when administered by oral, intraperitoneal, intravenous, and subcutaneous routes skin absorption is slow cholinesterase inhibitor in human ingestion can cause carbamate poisoning, which can be lethal when taken in large amount probable lethal oral dose in adult human estimated to be larger than other carbamate insecticides within the range... 

Acetylcholinesterase inhibitors has been a productive approach in the design of insecticides starting with the phosphate esters such as malathion and continuing on to carbamate esters such as carbaryl. For the latter, leads came from two carbamate reversible cholinesterase inhibitors used in medicine, the natural product physostigmine and the synthetic derivative, neostigmine. 

There are many cholinesterase inhibitors diminishing both AChE and BuChE activities to a comparable extent. However, there are a number of important exceptions the selectivity of some OP and carbamates for BuChE has been described by Aldridge (A4). Carbamates belong to a group of insecticides having a large variation in their effectiveness. They are biologically active because of their structural complementarity to the active surface of AChE and their consequent reaction as substrates with very low turnover numbers (A4, B2). Some carbamates inhibit selectively either AChE or BuChE (Bll, B22). The toxicity of carbamates is dependent on their ability to carbamylate AChE in different tissues and on other factors such as distribution, detoxification, and metabolization. 

A. May potentiate agents metabolized by the cholinesterase enzyme (eg, depolarizing neuromuscular blocking agents—succinylcholine, cocaine, esmolol), cholinesterase inhibitors (eg, organophosphate and carbamate insecticides), and other cholinergic agents (eg, pilocarpine). 

A. Oximes are used to treat poisoning caused by cholinesterase inhibitor insecticides and nerve agents, ie, organophosphates, mixtures of organophospho-ms and carbamate insecticides, or pure carbamate insecticide intoxication with nicotinic-associated symptoms. Because of its low toxicity, possible ineffectiveness if treatment is delayed until after the cholinesterase enzyme has aged, ability to reverse nicotinic as well as muscarinic effects, and ability to reduce atropine requirements, pralidoxime should be used early and empirically for suspected cholinesterase inhibitor poisoning. 

Cholinesterase inhibitors (e.g., organophosphate and carbamate insecticides). Long-term inhibition of cholinesterase activity produces cataracts in humans and monkeys. 

Carbamates are used as insecticides, nematocides, fungicides, and herbicides the toxicity of carbamate insecticides is similar to that of OP compounds and is based on the inhibition of ACHE. Also, carbamate metabolites may inhibit ACHE but are usually weaker inhibitors than the unchanged compound. Cholinesterase inhibition caused by carbamates is labile, of short duration, and rapidly reversible in fact, the half-life of the inhibited enzymes ranges between some minutes and 2 to 3 hours for RBC-ACHE and is on the order of some minutes for PCHE. Accumulation of cholinesterase activity on repeated exposures, as observed with OP compounds, does not occur with... 

Toxicity Bendiocarb is moderately toxic if it is ingested or absorbed through the skin. Skin absorption is the most likely route of exposure. It is a mild irritant to the skin and eyes.4 Like other carbamate insecticides, bendiocarb is a reversible inhibitor of cholinesterase, an essential nervous system enzyme. Symptoms of bendiocarb poisoning include weakness, blurred vision, headache, nausea, abdominal cramps, chest discomfort, constriction of pupils, sweating, muscle tremors, and decreased pulse. 

The commercial use of some organophosphates and carbamates as systemic insecticides has resulted in the synthesis of a large number of these anticholinesterases. Structural formulae and some data for these inhibitors are given in the reviews of Usdin (Ul), Aldridge and Reiner (A12), and Main (M4). Compounds which structurally resemble substrates are usually very good inhibitors of plasma cholinesterase. Thus, organophosphorus compounds modeled on acetylcholine are powerful inhibitors of the enzyme (Table 20). Quaternary aminophenylphosphates... 

The next three compounds are carbamates. Eserine is important because it is a very strong inhibitor of all cholinesterases and is used to verify that an esterase is a cholinesterase. Carbaryl also has a very high affinity to some cholinesterases, but a very low affinity to others. It is an important insecticide. Aldicarb was made to resemble acetylcholine. In spite of this, its affinity is very low (high Kd), but due to its high reaction rate (k+2 value), aldicarb is very toxic. 

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