Adrenochrome is a very unstable substance: it is completely destroyed in 4 min. by 1 % hydrochloric acid, and in 40 sec. by 1 % ammonia. At pH7-3 and 37 0C the red colour disappears in 35 min., and even under the optimum conditions for keeping the solution, at pH 4-0 and 0C, marked decomposition and melanin formation could be observed in 4-5 hours.
In the dry crystalline condition adrenochrome could be kept for several weeks, but on standing in a vacuum desiccator it decomposes to give a brown amorphous product. The crystalline substance appears to be a hydrate. The crystals decompose on heating at about 115-120°.
Adrenochrome is very soluble in water and crystallizes from water only on evaporation practically to dryness. It is also readily soluble in methyl alcohol. It is removed quantitatively from the aqueous solution by adsorption on charcoal, and can be eluted again from the charcoal with methyl alcohol.
The formula for adrenochrome is according to the equation:
C9H1303N+02-->C9H9O3N+2H20
Adrenochrome behaves as an ortho-quinone in that it is readily reduced by sulphur dioxide, hydrogen sulphide or palladium and hydrogen to give a colour- less leuco-compound which give the colour reactions of a catechol derivatives with ferric chloride. Leuco-adrenochrome is optically active.
The brilliant red colour of adrenochrome indicated that substitution in the benzene nucleus might have occurred.
Adrenochrome contains 4 hydrogen atoms less than adrenaline. Two of these hydrogen atoms have been removed in quinone formation: the other two hydrogen atoms have been removed in a reaction which has diminished the basicity of the nitrogen atom and at the same time appears to have effected a substitution in the benzene nucleus. This is best explained by ring closure between the nitrogen atom and the benzene nucleus to give a dihydroindole derivative IV.
The constitutional formula for adrenochrome gives an interpretation of all the properties hitherto observed and indicates that it may be related to the naturally occurring pigment hallachrome which was isolated from the polychaete Halla parthenopea.
Adrenaline is found to be rapidly oxidized by cytochrome and by the indophenol oxidase-cytochrome system. The oxidation product adrenochrome, although active as an oxidation carrier, is comparatively inactive as a vasoconstrictor.
The oxidation of adrenaline to adrenochrome is catalysed: (1) by a cyanide-insensitive system present in heart and skeletal muscle, and (2) by the cytochrome-indophenol oxidase system present in all tissues.
Adrenochrome has been reported to produce psychotomimetic effects following intravenous injection (A. Hoffer, H. Osmond, V. Smythies, J. Mental Sci. 100, 29 (1954). and H. Osmond, in Neuropharmacology (Josiah Macy, Jr. Foundation, New York, 1956), p. 183) and it has also been reported to be markedly elevated in the blood of normal subjects receiving lysergic acid diethylamide.
"pinkish adrenaline could be related to every hallucinogen then known".
"changes in perception, thinking and mood occurred, not of the extreme kind one sees with mescalin but mildly and insidiously, not unlike those seen early in schizophrenia."
"Plasma can convert adrenaline to adrenochrome and then adrenolutin enzumatically and adrenochrome in the brain is hallucinogenic."
"When the enormously powerful L.S.D.-25 is given to normal subjects, if psychological changes occur there is usually a dramatic and coincident rise in the levels of adrenochrome in the blood, and that adrenochrome injected intravenously is destroyed much less rapidly. Schizophrenic people seem less able to remove adrenochrome from blood than normals."