P-chloroamphetamine formation responsible for long-term depletion of brain serotonin after N-cyclopropyl-p-chloroamphetamine injection in rats

Abstract

After the injection of N-cyclopropyl-p-chloroamphetamine (N-cyclopropyl-PCA) into rats, p-chloroamphetamine (PCA) was identified in brain by high performance liquid chromatography with UV detection and was quantitated by that method and by spectroflurometric analysis involving reaction with fluorescamine. The identity of PCA in brains of rats treated with N-cyclopropyl-PCA was confirmed by mass spectrometry. The peak concentrations of PCA in brain occurred 4 hrs after N-cyclopropyl-PCA injection. Brain concentrations of PCA and of N-cyclopropyl-PCA were measured at 1 or 4 hrs, respectively, after the injection of various doses of PCA or of N-cyclopropyl-PCA into rats. The depletion of brain serotonin and 5-hydroxyindoleacetic acid (5-HIAA) was measured 1 week after injection of those same doses of PCA or N-cyclopropyl-PCA. Comparing peak concentrations of PCA with the degree of depletion of brain serotonin supported the interpretation that PCA formed metabolically accounted for the long-term depletion of brain 5-hydroxyindoles after injection of N-cyclopropyl-PCA in rats.