A Study of the Interaction of Copper with Selected Psychotropic Compounds

Abstract

The investigation of the interaction of copper (II) with two classes of compounds which are active in the central nervous system, the "sympathomimetic amines" (central nervous stimulants) and the phenothiazines (neuroleptics and major tranquillizers) began after noting several tenuously joined observations. The former class of compounds when administered in excess can produce varying symptoms from acute anxiety, (ephedrine) to a toxic psychosis, (amphetamine) so resembling schizophrenia that it could be used as a "model schizophrenia". The latter class could be used as a therapeutic control of the symptoms of schizophrenia, chlorpromazine being the best known member. Both classes of compounds act via dopamine systems in the brain and one of the active enzymes in the brain bringing about the removal of dopamine, dopamine β-hydroxylase, contains copper. Both classes have the ability to form complexes with copper. The “sympathomimetic amines" contain the aliphatic amino nitrogen atom whilst the phenothiazines also have the sulphur atom. The literature survey introduces the importance of trace metals and their complexes in health and disease and the consequence of their excess or deficiency is discussed. Previous work carried out in the preparation and characterization of complexes with the two classes of compounds is reported. The preparation of new complexes of copper (II) with selected "sympathomimetic amines" and selected phenothiazines is reported and their characterization, using various analytical techniques including thermogravimetric analysis, spectroscopic techniques: infrared, electronic and electronic spin resonance spectroscopy, magnetic and conductance measurements and x-ray analysis in certain cases. Measurements of ΔHvap for methylamphetamine and amphetamine have been made and ΔHdissoc for the dissociation of complexes of these bases have been determined. Several new complexes of each amine were isolated.