Inhibition 1-aminobenzotriazole

Figure 16 Mechanism of inhibition of the CYP enzyme inactivator ABT. Abbreviations CYP, cytochrome P450 ABT, 1-aminobenzotriazole.

Examples of enzyme-inhibiting chemicals are disulfiram, metyrapone, diethyl maleate, and 1-aminobenzotriazole. 

An inhibiting chemical slows the enzymatic metabolism of a toxic chemical. In this instance, if the uptaken chemical itself is the toxin, inhibition will slow the metabolism and intensify its action. If the metabolite of the absorbed xenobiotic is the toxic agent, inhibition will decrease the toxic affect. Vinyl chloride uptake in rats results in the lowering of cytochrome P450 and a corresponding loss of ability to metabolize other xenobiotics. Other inhibitors include diethyl maleate, which inhibits glutathione s-transferase and 1-aminobenzotriazole, which inhibits P450. 

Figure 2. Synergy of chlortoluron (CTU) by aminobenzotriazole (ABT) in wheat.(A) Inhibition of chlortoluron degradation, (B) Synergism of inhibition of wheat growth. Source Replotted from data in Cabanne et al. (33).

Figure 3. Tetcyclasis inhibition of chlortoluron catabolism in cotton. Note the much greater level of activity than that of aminobenzotriazole (Figure 2). Source Redrawn from data in Cole and Owen (36).

In considering whether MFO-catalyzed metabolism of herbicides is associated with cross-resistance in Lolium rigidum we have taken, initially, an indirect approach. Growth experiments with wheat showed that the MFO inhibitors aminobenzotriazole (ABT) and PBO synergized chlortoluron when the herbicide and inhibitors were added as a soil drench (34). This synergism was presumed to be due to the inhibition of MFO-catalysed metabolism of chlortoluron (27-29). Significantly, Kemp and Caseley (2) have shown that cross-resistant Alopecurus are relatively more susceptible to chlortoluron in the presence of ABT and other... 

S. Takemori, and H.D. Colby (1994). Inhibition of adrenal cytochromes P450 by 1-aminobenzotriazole in vitro. Selectivity for xenobiotic metabolism. BiocAew. Pharmacol. 48, 1421-1426. 

Sinai, C.J. and J.R. Bend (1996). Kinetics and selectivity of mechanism-based inhibition of guinea pig hepatic and pulmonary cytochrome P450 by N-benzyl-1-aminobenzotriazole and N-alpha-methylbenzyl-1 -aminobenzotriazole. Drug Metab. Dispos. 24, 996-1001. 

Mico, B.A., D.A. Federowicz, M.G. Ripple, and W. Kerns (1988). In vivo inhibition of oxidative drug metabolism by, and acute toxicity of l-aminobenzotriazole (ABT). Biochem. Pharmacol. 37,2515-2519. 

Cinnamic Acid 4-Hvdroxvlase - The p-hydroxylation of cinnamic acid in the biosynthesis of lignins by plants is mediated by a cytochrome P-450 enz3nne.l ° The cinnamic acid 4-hydroxylase of Jerusalem artichoke tubers is preferentially inactivated by 1-aminobenzotriazole in a tlme-and catalysis-dependent manner.The specific inhibition of cytochrome P-450 enzymes in plants provides a possible avenue for the design of new classes of herbicides and other crop-protection agents. 

In the animal model, based on variations between strains and males versus females, there was a correlation between the blood level of nevirapine and the incidence of rash (Chen et al. 2008). In addition, inhibition of metabolism by aminobenzotriazole led to higher nevirapine blood levels and rash at a lower dose, with lower levels of most metabolites. However, there was one metabolite... 

Balani SK, Zhu T, Yang TJ, Liu Z, He B, Lee FW. Effective dosing regimen of 1-aminobenzotriazole for inhibition of antipyrine clearance in rats, dogs, and monkeys. Drug Metab Dispos 2002 30 1059-1062. 

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