METABOLISM OF (-)-DEPRENYL AND PF-(-)-DEPRENYL IN BRAIN AFTER CENTRALAND PERIPHERAL ADMINISTRATION

We examined the cerebral metabolism of L-deprenyl and its fluoro-deriv ative pF-deprenyl, assaying the parent compounds, their metabolites de smethyl deprenyl, L-amphetamine, and L-methamphetamine, and the fluoro analogs of these metabolites. We compared the levels of the metabolit es after subcutaneous injection with those after intracerebral adminis tration (via microdialysis) of the parent compounds. The assay of the parent compounds and their metabolites was by GC-MS measurement of the components of brain microdialysate samples. After their subcutaneous administration, deprenyl, and F-deprenyl rapidly entered the brain and then their concentration decreased, with an approximate half-life of 4.5 h. After the intracerebral administration the diffusion from the s ite of administration was minor. A small fraction (a few percent) of t he intracerebrally administered deprenyl was metabolized in situ in th e brain possibly by a nonenzymatic process. Metabolism of pF-deprenyl was somewhat more rapid. The higher cerebral levels of metabolites aft er the subcutaneous administration indicate their exogenous origin-met abolism of parent compounds in the periphery and penetration of the br ain by the metabolites.