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Studies were performed to elucidate the effects of 1-[2-[bis (fluorophenyl) methoxy]ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893), a newly synthesized aryl-1,4-dialkyl-piperazine derivative, on turnover of dopamine and norepinephrine in the rat brain. The contents of both monoamines were not affected by I-893 at an oral dose of 10 mg/kg. The oral administration of 50-250 mg/kg produced a transient increase in dopamine content of the caudate nucleus and hypothalamus, and thereafter, the content dose-dependently decreased. Norepinephrine levels in the hypothalamus and frontal cortex were slightly decreased by I-893. I-893 potentiated the rate of alpha-methyl-p-tyrosine-induced depletion of dopamine and norepinephrine. The 3-methoxytyramine content in animals treated with pargyline was increased by I-893 in the caudate nucleus and olfactory tubercle. NSD-1015-induced accumulation of DOPA was suppressed by larger doses of I-893. Oral administration of I-893 (10-50 mg/kg/day) for 14 days slightly attenuated the inhibitory effects of the drug on the norepinephrine level, while it did not affect the inhibitory effect on the dopamine level. These results suggest that I-893 facilitates the release of dopamine and norepinephrine and/or inhibits the uptake of the monoamines in the presynaptic nerve terminals.

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Effects of 1-(2-(bis(fluorophenyl)methoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride(I-893) on turnover of dopamine and norepinephrine in the brain.