Analysis of p-Chloroamphetamine and a side-chain monofluorinated analogue in rat brain

Abstract

p-Chloro-α-fluoromethylphenylethylamine(fluoro-p-chloroamphetamine)(FpCA) has been shown in acute studies to be a less potent depletor of the neurotransmitter amine 5-hydroxytryptamine (5-HT) in brain than is p-chloroamphetamine (pCA). Gas Chromatographie assay procedures for FpCA and PCA have been developed in our laboratories and applied to preliminary measurements in brain tissue from rats injected intraperitoneally with pCA or FpCA. Groups of male Sprague-Dawley rats were injected with pCA (0.03 mmol/kg) or FpCA (0.05 or 0.1 mmol/kg) and killed 1, 2, or 4 hr later. The brains were analyzed for the halogenated amphetamines by gas chromatography with electron-capture detection (GC-ECD) following derivatization with pentafluorobenzenesulfonyl chloride (for pCA) or trichloroacetic anhydride (for FpCA). At the 0.05-mmol/kg dose, FpCA attained lower brain concentrations at 1, 2, and 4 hr after injection than did pCA at a considerably lower dose (0.03 mmol/kg). Even at the higher dose of FpCA used (0.10 mmol/kg), where concentrations of FpCA were higher than those of pCA initially, concentrations of FpCA had dropped below those of pCA by 4-hr. These preliminary results indicate that FpCA attains lower brain concentrations and is eliminated from the brain more rapidly than is the parent drug, pCA. However, differences in potency between FpCA and pCA on 5-HT depletion cannot be explained fully on the basis of obtained brain levels of the drug as even at time intervals where FpCA levels were higher than or equal to those of pCA, there was less depletion of 5-HT by the former drug.