The enzymic dephosphorylation and oxidation of psilocybin and pscilocin by mammalian tissue homogenates

Incubation of psilocybin with rat kidney homogenates caused a rapid liberation of its -OH congener, psilocin, through the action of alkaline phosphatase. The psilocin thus formed underwent further degradation to form a blue-colored product. This last step appeared to be catalyzed by an oxidative enzyme which was cyanide-sensitive, but not to β-phenylisopropylhydrazine, a monoamine oxidase inhibitor; its optimal activity was at pH 9.0. In many respects it resembles the characteristics of a phenolase type enzyme. The distribution of the phosphatase and oxidase enzymes in a number of tissues from several species of animals was also investigated. Psilocybin-dephosphorylating activity was highest in the rat and mouse kidney and the mucosa of the small intestine of guinea pig and rabbit. Oxidase activity was highest in the heart of all species and in the kidney of the rat and mouse. These experiments indicate that possibly in the intact animal psilocybin is rapidly dephosphorylated and is pharmacologically active as psilocin, while the duration of the effect might be controlled by the oxidation of the latter compound to an o-quinone type of structure.