Dopamine, Noradrenalin and Adrenalin Metabolism to Methylated or Chrome Indole Derivatives: Two Pathways or One?
Introduction
Indoles and their derivatives, the melanins, are among the most important compounds in the body, and perhaps the most neglected.1 This is not because they are uninteresting – they are very reactive, are present in every cell, and may be involved in most reactions in the body. Barr summarized the data, from which he concluded melanins were the organizing molecules that control growth and development and continuing function of the body.1 Perhaps they have been neglected because they are so common. We can hardly avoid seeing our own and everyone else’s melanin. More likely melanins have been neglected because they are too stable, while their immediate precursors are too unstable. Chemists did not have the techniques, skills, or patience to work with either the precursors or the final polymers. Simple indoles are derived from dopamine, noradrenalin, and adrenalin. These oxidized indoles – dopachrome, noradrenochrome, adrenochrome, and adrenolutin – are very reactive, as are all free radicals. Before they can be extracted from body fluids they will have to be trapped or stabilized by converting them into stable compounds. Adrenochrome forms a stable derivative with semicarbazone. In fact, the first workers who attempted to repeat our adrenochrome psychological studies, not knowing the difference between adrenochrome-semicarbazide and adrenochrome, and not knowing where to obtain adrenochrome, used the stable derivative that is not an hallucinogen. On the contrary, it has very mild anti-anxiety properties.2,3 Naturally, they did not find it to be an hallucinogen. Until these stable derivatives are isolated, the proof of their presence exists in the extraction of another class of stable derivatives, the melanins.
The sympathomimetic amines and their chrome indole derivatives are involved in the schizophrenias, in coronary disease, in aging, in some neurological diseases, such as Parkinsonism, and perhaps the organization and control of life itself.
Research scientists in fields other than psychiatry are leading the field.4,5 Research dermatologists interested in skin pigment and its diseases have been the pioneers in determining the structure and precursors of melanin. A few clinicians have become excited about the connection between arrhythmias and adrenochrome metabolism, but psychiatric interest remains very low. It was killed by two main factors: one political, one scientific. After NIMH, Washington, took a hostile attitude toward the Adrenochrome Hypothesis, it became clear to American investigators there would be little point in applying for grants. One of the major directors of research was advised personally during an on-site visit he could expect no funds unless he changed the direction of his research.
Scientifically, two lines of evidence were used to discredit the adrenochrome work. It was claimed it was not an hallucinogen because Rinkel, Hyde and Solomon had found adrenochrome semicarbazide not to be an hallucinogen. (1954) All the positive studies, including the double-blind studies in Czechoslovakia, were ignored. It was further claimed that all the adrenalin was metabolized by other pathways, leaving none to be oxidized into adrenochrome. In one “devastating” study using crude tracer techniques, it was proven that up to 120% of the adrenalin was accounted for by non indolic compounds.
In this report I will review briefly the history of the Adrenochrome Hypothesis of schizophrenia and show how it led to a number of interesting developments in medicine and psychiatry.
