3-(methyleneaminoxy)methylpiperidine derivatives as uptake inhibitors of biogenic amines in the brain synaptosomal fraction

Article abstract of DOI:10.1016/0223-5234(94)90197-X

A series of 3-(methyleneaminoxy)methylpiperidines (5a-h) and their corresponding N-methyl derivatives (6a-h) with a variety of substituents on the imino carbon were synthesized and tested for their potential antidepressant properties; their capacity to inhibit the re-uptake of biogenic amines (NA, 5-HT and DA) in rabbit brain synaptosomal fractions was also evaluated.The biological results obtained for the piperidine derivatives 5a-h and 6a-h and viloxazine 1, the reference drug, on the 3 re-uptake systems revealed that compounds 5 and 6 are generally able to inhibitbiogenic amine uptake.The IC50 values for 5 and 6 were often lower than that of viloxazine 1, in particular for the serotonin- and/or dopamine-uptake systems.A higher activity was found for compounds substituted with at least one phenyl ring on the imino carbon with respect to completely aliphatic systems, and for N-unsubstituted compounds with respect to N-methyl-substituted compounds. 3-(methyleneaminoxy)methylpiperidine derivative / NA uptake inhibitor / 5-HT uptake inhibitor / DA uptake inhibitor / antidepressant drug