Carbamates synergists

Metcalf RL, Fukuto CW, Fahmy S, El-Azis S, Metcalf ER (1966) Mode of action of carbamate synergists. J Agr Food Chem 14 555-562... 

Cinnamyl—sesamol ethers, eg (35), are useful as insect chemosterilants (111). 3,4-Methylenedioxyphenyl-3-halo-2-propynyl ethers (36, X = halogen) are synergists for carbamate insecticides (112). HaloaLkyl or haloalkenyl ethers, eg (37), show acaricidal and insect juvenile hormone activity (113). The first total synthesis of gibbereUic acid was from 2-methoxy-6-aLkoxyethyl-l,4-benzoquinone, a derivative of hydroxyhydroquinone (114). 

Although bicyclophosphates do not inhibit acetylcholinesterase, they exhibit a synergistic toxic effect with materials that do. Individuals who have had previous exposure to cholinesterase inhibitors such as nerve agents and commercial organophosphate or carbamate pesticides may be at a greater risk from exposure to bicyclophosphates. 

Examples of these include sesamin and sesamolin, both active principles of sesame oil, and piperonyl butoxide (PBO) and sesamex, both synthetic products. Although initially developed for use with pyrethrins, they have since been observed to synergize some, but not all, carbamates, organophosphates, pyrethroids, and organochlorines. In addition to the MDP compounds, another type of synergist called MGK 264 was developed to synergize the toxicity of pyrethroids and rotenone. The structure of piperonyl butoxide and MGK 264 are as follows ... 

Piperonyl butoxide is a synergist for carbamates, pyrethrins, pyrethroids, and rotenone. 

Pyrethrins and synthetic pyrethroids are among the safest of the topically applied ectoparasiticides, because of their selective toxicity for insects (mam-malian-to-insect toxic dose ratio is greater than 1000, compared with 33 for organophosphates and 16 for carbamate insecticides). In contrast to the very wide margin of safety for mammalian species, pyrethroids are toxic to fish. The synergistic action of pyrethrins and piperonyl butoxide (in combination preparations) is due to the inhibition by piperonyl butoxide of the microsomal enzyme system of some arthropods. Preparations of synthetic pyrethroids (permethrin, cypermethrin) often contain a mixture of drug isomers in varying proportions. 

Krause (1980) developed a method for determining methyl carbamate insecticides in fruit and vegetables using die HPLC technique. Krause and August (1983) later applied this method to the detection of other pesticides and synergists, including PBO. 

The ability of PBO in synergize cholinesterase-inhibiting insecticides has often been ignored when the mode of action of PBO is discussed. Moore field (I95KJ presented detailed data on this subject and showed that both aromatic and heterocyclic carbamates can be potentiated with PBO. A graphical presentation of data is reproduced in Fig. 19.3 on the effect of adding PBO to iwo carbamate insecticides to control house flics. This is of particular interest in that application was only made to female flies by individual measured drops - much more precise and relevant to effective control than spray applications to Hies of both sexes. This was a classic demonstration of the powerful synergistic action of PRO... 

Aryl-acylamidase inhibitors. Rice is resistant to the herbicide propanil due to a rice specific aryl-acylamidase which degrades the herbicide. Various carbamate and organophosphorothioate insecticides were found to be incompatible with propanil because they prevented propanil degradation. This was found to be due to a direct inhibition of this enzyme (47, 48). Such insecticides or their derivatives can be " rational" synergists when this enzyme is found to be active in degrading herbicides in weeds, and must be suppressed. 

The oxidation, which is the bioactivation reaction, is inhibited by piperonyl butoxide, whereas the demethylation reaction catalyzed by glutathione transferase is not inhibited. Piperonyl butoxide is therefore an antagonist to methyl-parathion, but a synergist to most other pesticides, including carbamates and pyrethroids. Pyrethrins are very quickly detoxified by oxidation of one of the methyl groups, catalyzed by the CYP enzymes. 

The above compounds have been used as synergists of pyrethrum and synthetic pyrethroids, such as allethrin, cyclethrin and others. Later investigations showed that these compounds can also synergise other insecticides, primarily carbamates and DDT. Piperonylbutoxide and sesamex proved to be the most efficient in this respect however, the latter is unsuitable for practical use because of its sensitivity to light and humidity. 

Felling and co-workers (Felling and Rachlin, 1968 Barnes and Felling, 1969 Felling et al 1970) found an interesting group of synergists of the carbamate type insecticides, the phenyl 2-propynyl ethers. The most active member of this series is the 2-nitro-4-chloro derivative (24). 

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