Effects of pre- and post-treatment with EXP 561 on the amine-depleting effects of p-chloroamphetamine and 6-hydroxydopamine in rats.

EXP 561, 4-phenyl-bicyclo(2,2,2)octan-1-amine hydrochloride monohydrate, antagonized brain serotonin depletion by p-chloroamphetamine and heart norepinephrine depletion by 6-hydroxydopamine in rats. The antagonism of p-chloroamphetamine action occurred with post- as well as pre-treatment with EXP 561. Simultaneous injection of EXP 561 with p-chloroamphetamine initially antagonized serotonin depletion but the effect diminished by 24 hrs. The antagonism of 6-hydroxydopamine action could be produced only by pre-treatment with EXP 561, post-treatment having no effect. When EXP 561 was injected simultaneously with 6-hydroxydopamine, its antagonistic effect did not decline with time. The duplications of these findings for the interpretation of data on uptake inhibitor antagonism of amine depletors are discussed.