Monooxygenase inhibitors

Also included in these in vivo studies were trials with the microsomal monooxygenase inhibitor, SKF 525-A. As in the cases of the susbtrates, no remarkable effects were observed. The fate of the inhibitor is unknown. To date, SKF 525-A exposures have not been coupled with measurements of oxidative metabolism. 

Microsomal monooxygenase inhibitors that form stable inhibitory complexes with P450, such as SKF-525A, piperonyl butoxide, and other methylenedioxphenyl compounds, and amphetamine and its derivatives, can be readily investigated in this way. This is because the microsomes isolated from pretreated animals have a reduced capacity to oxidize many xenobiotics. 

Hunt D. W. A. and Smirle M. J. (1988) Partial inhibition of pheromone production in Dendroctonus ponderosae (Coleoptera Scolytidae) by polysubstrate monooxygenase inhibitors. J. Chem. Ecol. 14, 529-536. 

Tyrosinase inhibitors prevent browning in foodbecause they inhibit the oxidation caused by the enzyme tyrosinase. Cuminaldehyde is identified as a potent mushroom tyrosinase monophenol monooxygenase inhibitor from cumin seeds, ft inhibits the oxidation of L-3,4-dihydroxyphenylalanine (l-DOPA) by mushroom tyrosinase with an ID50 of 7.7g/ml (0.05 mM). Its oxidized analogue, cumic acid (p-isopropylbenzoic acid), also inhibits this oxidation with an 1D50 of 43g/ml (0.26mM). These two inhibitors affect mushroom tyrosinase activity in different ways (Kubo and Kinst-Hori, 1998). 

A number of classes of monooxygenase inhibitors, in addition to methylene-dioxyphenyl compounds, are now known to form metabolic-intermediate complexes including amphetamine and its derivatives and SKF-525A and its derivatives. 

A number of inhibitors of methyl farnesoate epoxidase of Blaberus glganteus corpora allata have been described (18). They include typical cytochrome P-450 monooxygenase inhibitors such as methylenedloxyphenyl compounds and substituted imidazoles. In assays of JH III biosynthesis by Perlplaneta amerlcana CA in vitro some methylenedloxyphenyl compounds were shown to inhibit hormone production at moderate to high concentrations (19). Both methylenedloxyphenyl compounds and terpenoid imidazoles have also some anti-juvenile hormone activity in Lepidoptera (7, 20). 

A-demethylation of 1,1-dimethylhydrazine by rat and hamster liver microsomes in vitro required the presence of NADPH and oxygen and was decreased by the addition of flavin-containing monooxygenase inhibitor (methimazole) but not by the addition of cytochrome P-450 inhibitors (Prough et al. 1981). 

Table 4. The suppression of herbicide degradation by monooxygenase inhibitors...

Table 10.1. Effect of Monooxygenase Inhibitors on the Metabolism of Chlortoluron in Maize and Cotton Suspension Cultures" ...

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