Biotransformation of xenobiotics by amine oxidases

Although the cytochrome P450 (CYP) system ranks first in terms of catalytic versatility and the wide range of xenobiotics it detoxifies or activates t o reactive intermediates, the contribution of amine oxidases and in particu lar of monoamine oxidases (MAOs) to the metabolism of xenobiotics is far fr om negligible but has been largely neglected, In this review on the involvement of amine oxidases in the metabolism of xe nobiotics, the major characteristics reported for the CYP system (protein, reaction, tissue distribution, subcellular localisation, substrates, inhibi tors, inducers, genetic polymorphism, impact of different physiopathologica l conditions on the activity, turnover) will be compared, whenever possible , with the corresponding characteristics of amine oxidases (MAOs in particu lar). The knowledge of the involvement of MAO-A, -B or both in the metabolism of a drug allows us to predict interactions with selective or non-selective MA O inhibitors (e.g. the metabolism of a drug deaminated by both forms of MAO is not necessarily inhibited in vivo by a selective MAO-A or -B inhibitor) . If a drug is metabolized by MAOs, competitive interactions can Occur with other drugs that are MAO substrates, e.g. with beta -adrenoceptor agonists and antagonists, prodrugs of dopamine, serotonin 5-HT1-receptor agonists a s well as with primaquine, flurazepam and citalopram. Moreover, the knowled ge of the involvement of MAOs in the metabolism of a drug may suggest possi ble, although not obligatory, interactions with tyramine-containing food or drink, with over the counter medicines sold to relieve the symptoms of cou ghs and colds (generally containing the indirectly-acting sympathomimetic a mine phenylpropanolamine) or with phenylephrine-containing preparations. Finally, biotransformation by amine oxidases, as by CYP, does not always le ad to detoxication but can produce toxic compounds.