The 3-and 4benzoylpiperidines and 3-benzoylpyrrolidines were prepared by the reaction of l-acetylisonipecotoyl or 1-acetylnipecotoyl chloride with a substituted aromatic compound under Friedel-Crafts conditions or by treatment of the cyanopiperidines and pyrrolidines with an arylmagnesium halide. Alkylation gave the I-substituted compounds which were evaluated as CNS depressants. The I-substituted 4(p-fluorobenzoyl)piperidines were the most active compounds, several of which were more potent than chlorpromazine, triperidol, or haloperidol in the fighting mouse assay.

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Flutamide (FTA), an anti-androgenic compound, inhibited the effects of methyltestosterone (MT) on the weight of the ventral prostate, seminal vesicles and levator ani in male castrate mice. Castration prevented the development of aggressive behavior in mice isolated for 3 weeks. While chronic administration of MT to castrate isolated mice returned the incidence of fighting behavior to control values, chronic administration of FTA + MTdid not significantly reduce the incidence of fighting as compared to castrate + MT values. These results suggest that the mechanism for androgen stimulation of secondary sex organ weight may differ from that involved in the development and maintenance of aggression resulting from isolation.

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