Carbamates insecticides

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

Physostigmine (eserine) is a carbamate found in the calabar bean (Physostigma benenosum), which acts as an anticholinesterase. It was used in West Africa in witchcraft trials by ordeal. It has also been used in human medicine. Insecticidal carbamates are structurally related to it and also act as anticholinesterases (Ballantyne and Marrs 1992). 

Cambon, C., C. Declume, and R. Derache. 1979. Effect of the insecticidal carbamate derivatives (Carbofuran, Pirimicarb and Aldicarb) on the activity of acetylcholinesterase in tissues from pregnant rats and fetuses. Toxicol. Appl. Pharmacol. 49 203-208. 

Lebrun, P., A. de Medts, and G. Wauthy. 1981. Eco-toxicologie comparee et bioactivite de trois insecticides carbamates sur une population experimentale de vers de terre, Lumbricus herculeus. Pedobiologia 21 225-235. 

This technique has been applied to the determination of chlorinated insecticides, carbamate insecticides and substituted urea type herbicides in soil and chloroaliphatic hydrocarbons in non-saline sediments. Separation is usually achieved on thin layers of silica gel or alumina. 

Carbamate Insecticides. Carbamate insecticides interact with acetylcholinesterase in exactly the same way as OPs, with the hydroxyl group in the serine at the enzyme s active site attacking the carbamate residue in the insecticide. However, the binding to the active site is reversible. Typical carbamate insecticides are shown in Figure 3.4. 

Insecticidal carbamates also inhibit the enzyme acetylcholinesterase by transferring a carbamoyl group to the active hydroxyl. However, they differ from the phosphates in that they inhibit the enzyme reversibly and so a better fit at the active site is required for high activity. In consequence, a narrower range of structures is active. The chemistry, biochemistry, metabolism and toxicology of carbamate insecticides have been thoroughly reviewed (B-76MI10702). 

The discovery of insecticidal carbamates arose independently from studies on the naturally occurring toxin physostigmine (86), and from research on insect repellants. The latter produced some pyrazoles of which isolan was an example (87) (68MI10701), derived from 3-methyl-5-pyrazolone which is made by condensation of hydrazine with ethyl acetoacetate. 

ED Magallona. Gas chromatographic determination of residues of insecticidal carbamates. Residue Reviews 56 1-73, 1975. 

Figure 15.8 Carbamic acid and three insecticidal carbamates.

The increased use of derivatisation reactions is evident from the gradual increase in the number of publications dealing with the subject. Figure 1 shows the yearly variation in numbers of publications dealing with derivatisation in pesticide analysis over the period 1963 to 1978. While the interest in derivatisation techniques in organophosphorus insecticide analysis has remained fairly constant and a low level of activity, the OC insecticides underwent an increased period of attention from 1968-1972 which has stablized over the last few years. It is in the insecticidal carbamate and herbicide areas that an overall steady increase in the use of derivatisation reactions for quantitative and con-... 

Lawrence [475] and Ryan and Lawrence [476] chromatographed insecticidal carbamates and other agricultural chemicals in the form of perfluorinated acyl derivatives. Of these they recommended HFB derivatives as most suitable. They prepared them by treatment with HFB anhydride in benzene in the presence of trimethylamine, as follows. A 15-jul volume of HFB anhydride and 0.4 ml of 0.1 M trimethylamine in benzene were added to 1—10 /rg of insecticide (dried extract of a food sample) in a 20-ml test-tube. 

Fig. 12.7 Insecticidal carbamates. The numbers below each structure indicate approximate oral LD50 values (mg kg-1) in mice or rats. Values taken from Ref. [28].

The application of the above method to the syntheses of insecticides carbamates Carbofuran (entry 4, table 3-27) and Aldicarbe was briefly studied. Thus, Carbofuran was readily obtained in 79% yield from 1-chloroethyl benzofu-ranyl carbonate which was itself obtained in 89% yield from the corresponding hydroxy benzofuran. 

AChE Organophosphorus insecticides Carbamates Inhibits the hydrolysis of ACh, causing overstimulation of the cholinergic synapses Nicotinic and muscarinic effects... 

O Brien (1971) pointed out that the majority of insecticidal carbamates are aromatic, suggesting the involvement of n-n interactions in binding them to the enzyme. Thus compound 7 is about 1000 times as active as its cyclohexyl analogue. 

Cambon, C,. Deelume, C.. and Deraehe, R. (1980). Fetal and maternal rat brain acetylcholinesterase isoenzymes changes following insecticidal carbamate derivatives poisoning. Arch. 7anccj/. 45, 257-262. 

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