Metabolism mode of action

K. A. HassaH, The Biochemistry and Uses of Pesticides Structure, Metabolism, Mode of Action and Uses in Crop Protection, 2nd ed., VCH VedagsgeseUschaft, Weinheim, Germany, 1990. 

Schonfeld G. Metabolic modes of action of statins in the hyperlipoproteinemias. Atherosclerosis 1998 141 203-207. 

Hashimoto, K. Kanai, R. (1965) Studies on the toxicology of acrylonitrile, metabolism, mode of action and therapy. Ind. Health, 3, 30-45... 

A. Modes of Toxic Action. This includes the consideration, at the fundamental level of organ, cell and molecular function, of all events leading to toxicity in vivo uptake, distribution, metabolism, mode of action, and excretion. The term mechanism of toxic action is now more generally used to describe an important molecular event in the cascade of events leading from exposure to toxicity, such as the inhibition of acetylcholinesterase in the toxicity of organophosphorus and carbamate insecticides. Important aspects include the following ... 

Comparative toxicology is the study of the variation in toxicity of exogenous chemicals toward different organisms, either of different genetic strains or of different taxonomic groups. Thus the comparative approach can be used in the study of any aspect of toxicology, such as absorption, metabolism, mode of action, and acute or chronic effects. Most comparative data for toxic compounds exist in two areas—acute toxicity and metabolism. The value of the comparative approach can be summarized under four headings ... 

C. J. Kensler2 55 Arthur D. Little, Inc. Sr. Vice President in Charge, Life Sciences Div. Pharmacology, Biochemistry Nutrition cancer tissue metabolism mode of action of carcinogenic agents industrial toxicology... 

Haussler, M. R. Vitamin D3 Metabolism, Mode of Action, and Assay of Circulating Hormonal Form. In Vitamin D and Problems Related to Uremic Bone Disease (Norman, A. W., ed.), p. 25. Berlin Walter de Gruyter and Co. 1975. 

HassaH KA. The biochemistry of pesticides structure, metabolism, mode of action and uses in crop protection. 2nd ed., Verlag Chemie, Weinheim, 1990. 

Ampicillin—see Penicillin, D-n-aminobenzyl-Amprolium coccidiostat mode of action, 1, 212 as veterinary product, 2, 515 Amquinsin, 2, 517 Amylobarbitone metabolism, 1, 237 Anabasine, 2, 511 synthesis, 2, 385 Anabasine, N-methyl-N -oxide... 

Metronidazole — see also Imidazole, 1-(2-hydroxy-ethyl)-2-methyl-5-nitro-antiprotozoal activity, 1, 180 veterinary use, 1, 208 mode of action, 1, 208 Metyrapol metabolism, 1, 234 Metyrapone... 

Much work has also 4)een done bearing directly or indirectly on the mode of action of quinine and other anti-malarial drugs. The absorption, distribution and metabolism of quinine has been investigated by various workers of whom Kelsey, Ceiling, Oldham and Dearborn (1944)... 

Miyamoto J, Sato Y, Kadota T, et al. 1963a. Studies on the mode of action of organophosphorus compounds. Part I. Metabolic fate of P32 labeled sumithion and methylparathion in guinea pig and white rat. Agric Biol Chem 27 381-389. 

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

Hassall, K.A. (1990). A readable student text, particularly useful for the metabolism and mode of action of herbicides and fungicides. 

Hodgson, E. and Levi, P. (1994). A multiauthor text dealing in depth with some aspects of biochemical toxicology highly relevant to the present topic. Examples of metabolism and mode of action of insecticides, and PAHs. 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

In general, it is easier to use models such as these to predict the distribution of chemicals (i.e., relationship between exposure and tissue concentration) than it is to predict their toxic action. The relationship between tissue concentration and toxicity is not straightforward for a diverse group of compounds, and depends on their mode of action. Even with distribution models, however, the picture can be complicated by species differences in metabolism, as in the case of models for bioconcentration and bioaccumulation (see Chapter 4). Rapid metabolism can lead to lower tissue concentrations than would be predicted from a simple model based on values. Thus, such models need to be used with caution when dealing with different species. 

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