ELEVATION OF EPINEPHRINE CONCENTRATION IN RAT-BRAIN BY LY51641, A SELECTIVE INHIBITOR OF TYPE-A MONOAMINE-OXIDASE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 32  (2) , 207-221
Abstract
LY51641, N-[2-(o-chlorophenoxy)ethyl]cyclopropylamine hydrochloride, selectively inhibited type A monoamine oxidase (MAO) (measured with 100 .mu.M 14C-serotonin as substrate) without inhibiting type B MAO (measured with 12.5 .mu.M 14C-phenylethylamine as substrate) in rat brain. The inhibition of type A MAO was accompanied by an increase in epinephrine [E] concentration in hypothalamus. The absolute concentration of E in rat hypothalamus is low relative to norepinephrine [NE] and dopamine [D], but the percentage increase in E after LY51641 was greater than the percentage increase in D or NE. The inhibition of type A MAO activity and increase in hypothalamic E concentration following a single 30 mg/kg dose of LY51641 persisted for at least 10 days. Both effects were seen at doses as low as 0.03 mg/kg of LY51641. A 0.2 mg/kg dose of LY51641 given daily for 5 days retained selectivity in inhibiting type A MAO and increased E concentration. Two analogs of LY51641 of differing selectivity elevated E concentration to a degree related to percentage inhibition of type A MAO, and the effect of LY51641 was antagonized by pretreatment with harmaline, a short-acting reversible inhibitor of type A MAO. In rat hypothalamus, E oxidation occurs by type A, not type B MAO.