Inhibition of human and canine diamine oxidase by drugs used in an intensive care unit: relevance for clinical side effects?

Abstract

Three hundred and forty-one drugs, commonly used in intensive care units (ICU), were chosen for an investigation of possible activation or inhibition of the histamine metabolizing enzyme diamine oxidase (DAO). After examination of 164 substances, using both canine and human DAO in an in vitro screening test, 61 agents inhibited DAO activity to various degrees. Of these, 44 inhibited the enzyme from both species, 4 inhibited the canine enzyme only and 13 the human DAO only. No compound tested was able to enhance the enzyme activity. The inhibiting agents included representatives of all major therapeutic groups. A particularly strong inhibition was observed with the neuromuscular blocking drugs d-tubocurarine, pancuronium and alcuronium, however, the other commonly used neuromuscular blocking drug, suxamethonium, was without effect. Similarly with the cephalosporines, cefotiame and cefuroxime caused a marked inhibition of the human DAO activity, whereas another regularly-used substance of this class, cefotaxime, inhibited neither the human nor the canine enzyme in concentrations up to 10(-3) M. The observation that within a given therapeutic group some members inhibit and others do not, could be useful in choosing a therapy concept which minimizes the risk of a more severe 'histamine' reaction in seriously ill patients.