INVIVO EFFECTS OF LR5182, CIS-3-(3,4-DICHLOROPHENYL)-2-N,N-DIMETHYLAMINOMETHYL-BICYCLO-[2,2,2]-OCTANE HYDROCHLORIDE, AN INHIBITOR OF UPTAKE INTO DOPAMINE AND NOREPINEPHRINE NEURONS

cis-3-(3,4-Dichlorophenyl)-2-N,N-dimethylaminomethyl-bicyclo-[2,2,2]-octane hydrochloride, (LR5182) antagonized the depletion of heart norepinephrine by 6-hydroxydopamine but not the depletion of brain serotonin by p-chloroamphetamine in mice. Norepinephrine depletion was antagonized by LR5182 following α-methyl-m-tyrosine injection into rats both in the cerebral hemispheres and in the hypothalamus. The drug also antagonized dopamine depletion in the cerebral hemispheres but did not antagonize epinephrine depletion in the hypothalamus in these rats. The concentration of α-methyl-m-tyramine and of metaraminol in the cerebral hemispheres of rats was lowered by LR5182 after α-methyl-m-tyrosine injection; since these amine metabolites are taken up and retained by dopamine and norepinephrine neurons, respectively, this lowering is a further indication of the inhibition of uptake into dopamine and norepinephrine neurons by LR5182. The elevation of brain DOPAC (3,4-dihydroxyphenylacetic acid) was significantly enhanced by LR5182 following spiperone injection, an effect characteristic of a particular subclass of dopamine uptake inhibitors. © 1979.