Effects of Some Centrally Acting Drugs on Caeruloplasmin


The copper-containing oxidase caeruloplasmin is studied in this chapter as a potential model for those receptors in the CNS with which certain centrally acting drugs must interact in order to produce their characteristic effects. Lysergic acid diethylamide (LSD), and to a lesser degree ibogaine and 2–bromo–LSD, inhibit the enzymic oxidation of 5-HT but accelerated the oxidation of NA. Harmine and harmol inhibit the enzymic oxidation of both substrates. Phenylethylamines and anticholinergics with reported central activity have no effects on the enzymic oxidation of NA and 5-HT. Some of the drugs used in the treatment of mental illness affect the caeruloplasmin-catalysed oxidation of NA and 5-HT. Tranquillizers of the phenothiazine type, for example, accelerate the oxidation of both substrates, whilst anti-depressant drugs (other than monoamine oxidase inhibitors) inhibit the oxidation of both substrates. The results have led to the tentative suggestion that caeruloplasmin, or an enzyme with similar properties, may be of importance in controlling the relative concentrations of NA and 5-HT in some areas of the brain. The relevance of this suggestion to the mode of action of LSD, and other centrally acting drugs are discussed here.



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