Cytochrome P450 enzymes selectivity

Lanza, D. L. Yost, G. S. Selective dehydrogenation/oxygenation of 3-methylindole by cytochrome P450 enzymes. Drug Metab. Dispos. 2001, 29, 950-953. 

Some selective serotonin re-uptake inhibitors are powerful inhibitors of cytochrome P450 enzymes and the metabolism of e.g. tricyclic antidepressants can be inhibited resulting in serious toxicity. Additive sedation can be expected when given in combination with CNS depressants such as benzodiazepines but also with alcohol. Selective serotonin re-uptake inhibitors should not be used in combination with monoamine oxidase inhibitors as fatal reactions have been reported. 

Harvey AT, Preskorn SH. Cytochrome P450 enzymes interpretation of their interactions with selective serotonin reuptake inhibitors (Part II). J Clin Psychopharmacol 1996 16 345-355. 

Ketoconazole was the first oral azole introduced into clinical use. It is distinguished from triazoles by its greater propensity to inhibit mammalian cytochrome P450 enzymes that is, it is less selective for fungal P450 than are the newer azoles. As a result, systemic ketoconazole has fallen out of clinical use in the USA and is not discussed in any detail here. Its dermatologic use is discussed in Chapter 61. 

Guengerich FP. Catalytic selectivity of human cytochrome P450 enzymes relevance to drug metabolism and toxicity. Toxicol Lett 1994 70 133-138. 

Verras, A., Kuntz, I.D., Ortiz De Montel-lano, P. R. Computer-assisted design of selective imidazole inhibitors for cytochrome P450 enzymes. J. Med. Chem. 2004, 47, 3572-3579. 

TABLE 5—3. Cytochrome P450 Enzyme Family and Selected Substrates... 

Kwon, H., Sahali, Y, Skipper, P. L., and Xannenbaum, S. R. (1992). Oxidation of cyclopenta[cmouse liver microsomes and selected cytochrome P450 enzymes. Chem Res Toxicol 5,... 

Differential selectivity in carbamazepine-induced inactivation of cytochrome P450 enzymes in rat and human liver. Arch. Toxicol. 75, 538-543. 

Tierney, D.J., A.L. Haas, and D.R. Koop (1992). Degradation of cytochrome P450 2E1 Selective loss after labilization of the enzyme. Arch. Biochem. Biophys. 293, 9-16. 

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