Metabolism early research

Chloro- -triazines have been shown to be metabolized in plants by one of four competing processes hydrolytic dehalogenation, oxidative /V-dcalkylation, nucleophilic displacement of the chlorine atom with glutathione, and ami-nation or deamination reactions. Much of the early research focused on the first three processes and attempted to determine the relative importance of each process to herbicide tolerance. The relevant research undertaken between 1961 and 1973 will be discussed. 

Montgomery and Freed (1964) reviewed the early research metabolism of triazine herbicides by plants and concluded that there was a good correlation between resistance in plants and the extent of their metabolism. A common pathway of degradation for these chemicals was indicated by the presence of 2-hydroxy analogs. 

Having said this, no criticism of the early researchers in the field of steroid hormone metabolism is intended they could only experiment with materials currently available to them. 

Westerink WM, Stevenson JC, Horbach GJ, Schoonen WG (2010) The development of RAD51C, Cystatin A, p53 and Nrf2 luciferase-reporter assays in metabolically competent HepG2 cells for the assessment of mechanism-based genotoxicity and of oxidative stress in the early research phase of drug development. Mutat Res 696 21 0... 

Dissimilarities in the metabolism of the kavalactones between humans and rats undoubtedly demonstrate the difference in metabolic pathways between the two species. Differences may also be related to the fact that the kavalactones were given as individual components in the rat, whereas they were administered in humans as a mixture from an aqueous extract of the kava rootstock. These intriguing results with respect to the metabolism of kavalactones may also explain the observation by many early researchers that the physiological effects of the kava extract were more pronounced than with the individual lactones (Klohs etal., 1959b Steinmetz, I960 Meyer, 1979). Therefore the lactones may be acting synergisticaUy or may facilitate each other s transport... 

The history of cytochrome P450 (P450) really began with studies on the metabolism of drags, carcinogens, and steroids. The early research in these fields necessarily involved animal models, but the intent was always to imderstand the human systems in the context of the enzymes catalyzing the observed transformations. 

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

Lin, J.H. and Rodrigues, A.D. 2001. In vitro models for early studies of drug metabolism. In Pharmacokinetic Optimization in Drug Research Biological, Physicochemical and Computational Strategies. Testa, B. et al., Eds., Wiley, New York, p. 217. 

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