Interaction of some centrally active drugs with caeruloplasmin

Abstract

Centrally active drugs such as D-lysergic acid diethylamide (LSD), and to a lesser extent ibogaine and 2-bromo-LSD, are shown to inhibit the caeruloplasmin-catalysed oxidation of 5-hydroxytryptamine but accelerate the oxidation of noradrenaline and dopamine. Harmine and harmol inhibit the enzymic oxidation of all three substrates. Centrally active anticholinergics and substituted phenylethylamines do not affect the enzymic oxidation of these substrates. Some drugs used in the treatment of mental illness affect the caeruloplasmin-catalysed oxidation of noradrenaline, dopamine and 5-hydroxytryptamine. Tranquillizers of the phenothiazine class, for example, accelerate the oxidation of all three substrates whilst antidepressant drugs (other than monoamine oxidase inhibitors) inhibit the oxidation of all three substrates. The results obtained show that caeruloplasmin cannot be generally used as a model for those receptors with which some centrally active drugs must interact to produce their characteristic effects; they do, however, suggest that caeruloplasmin, or an enzyme with similar properties, may be of importance in controlling the relative concentrations of noradrenaline, dopamine and 5-hydroxytryptamine in those areas of the brain where these compounds act as neuro-transmitters.