Methylation, carbamates metabolism

Modified from Zakour, H.R. 1980. Toxicity, Uptake and Metabolism of the /V-methyl-carbamate Pesticide Carbofuran by the Freshwater Bivalve Mollusc Glebula rotundata (Lamarck). Ph.D. Thesis, Rice University, Houston. 148 pp. 

N-methyl carbamates do not need activation to inhibit ChEs. However, at least in the case of aldicarb, inhibition increases with metabolism. Aldicarb is rapidly oxidized to the relatively stable aldicarb sulfoxide, which in turn is more slowly metabolized to aldicarb sulfone, a stronger AChE inhibitor. These products are then detoxified by conversion to oximes and nitriles, which in turn are degraded to aldehydes, acids, and alcohols. Procarbamate derivatives were... 

FIG. 4. Metabolic. scheme for the oxidative and B-esterase metabolism of carbaryl to the ring and side chain hydroxylaied methyl carbamates and the major metabolite a-naphthol. 

The results of a comparative metabolism study of an aryl-sulfenyl derivative of carbofuran [2,2-dimethy1-2,3-dihydro-benzofuranyl-7 -methyl-N-(2-toluenesulfenyl)carbamate] in the house fly and white mouse Indicated the selective action of this compound to be a consequence of different metabolic pathways in insects and mammals (12). The arylsulfenyl group on the carbamate moiety allows the mammal to carry out metabolic reactions leading to less toxic products which are rapidly conjugated, while the toxic parent methylcarbamate is formed in the insect. 

The carbamates exhibit relatively low toxicities in mammals because they are rapidly metabolized by them. Initially the MFOs are involved in an oxidative transformation. In the aryl methyl... 

Chroman, 4-( p-hydroxyphenyl)-2,2,4-trimethyl-X-ray studies, 3, 622 Chroman, 2-methoxy-synthesis, 3, 806 Chroman, 5-methoxy-synthesis, 3, 778 Chroman, 7-methoxy-synthesis, 3, 778 Chroman, 8-methoxy-acylation, 3, 732 Chroman, 2-methoxy-2-methyl-synthesis, 3, 780 Chroman, 2-methyl-synthesis, 3, 785 Chroman, 5-methyl-reactivity, 3, 732 Chroman, 6-nitro-synthesis, 3, 784 Chroman, 4-phenyl-synthesis, 3, 783 Chroman, thio-metabolism, 1, 241 Chroman, 5,6-thio-2-substituted metabolism, 1, 241 Chromanamines H NMR, 3, 580 Chroman-3-amines conformation, 3, 630 (S) -Chroman-2-carbaldehyde synthesis, 3, 779 Chromancarbaldehydes synthesis, 3, 782 Chroman-4-carbamic add synthesis, 3, 782 (R)-Chroman-2-carboxylic add methyl ester... 

Since MIC is highly reactive, it is not metabolized in the classical sense. Conjugation of MIC with glutathione (GSH) forming an adduct S-(N-methyl-carbamoyl) glutathione, and corresponding cysteine adduct, S-(N-methylcarbamoyl) cysteine appears to represent an important pathway of biotransformation of MIC in the rats exposed to MIC intraper-itoneally. The reaction of MIC with GSH and with cysteine is reversible, and can provide a source of free MIC in the tissues. It is speculated that these carbamate thioester conjugates of MIC may actually contribute to toxic effects of MIC. Similar studies in experimental animals exposed to MIC by the inhalation route have not been reported. 

In the sedative-hypnotic series, most of the acetylenic alcohols are used as carbamic esters meparfynol, ethinamate, etc. The bromoethynyl moiety confers an acidity comparable to that induced by a trichloromethyl group (compare for example chlorobutanol with 3-methyl-pentyne-3-ol). Bromoethynylcyclohexanol is sufficiently acidic to form salts its bismuth salt was used for a while as an antisyphilitic drug under the name of biarsamide. In the steroid series the metabolism of the ethynyl group can lead (by hydration of the triple bond) to 17 a-methylketones. 

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