Depletion of epinephrine in rat hypothalamus by Ro 4-1284: influence of pargyline and harmaline.

Ro 4-1284, 2-ethyl-2,3,4,6,7,11b-hexahydro-3 isobutyl-9,10-dimethoxy-2H-benzo[a]quinolizin-2-ol hydrochloride, depleted epinephrine in rat hypothalamus; the depletion occurred within 1 hr and persisted at 24 hr. The rapid lowering of epinephrine by Ro 4-1284 was antagonized by pargyline, a monoamine oxidase inhibitor, which alone elevated epinephrine concentration. The ability of pargyline to antagonize epinephrine depletion by Ro 4-1284 was prevented by co-treatment with harmaline, which protects aginst type A but not type B monoamine oxidase inhibition by pargyline. Pargyline also antagonized the Ro 4-1284-induced depletion of norepinephrine in hypothalamus and of norepinephrine and dopamine in cerebral hemispheres, and these effects of pargyline were also prevented by co-treatment with harmaline. The results suggest that epinephrine in rat brain, like norepinephrine and dopamine, is destroyed primarily by type A monoamine oxidase.