Elevation of epinephrine concentration in rat brain by LY51641, a selective inhibitor of type A monoamine oxidase.
LY51641, N-[2-(o-chlorophenoxy)ethyl]cyclopropylamine hydrochloride, selectively inhibited type A monoamine oxidase (MAO) (measured with 10 microM 14C-serotonin as substrate) without inhibiting type B MAO (measured with 12.5 microM 14C-phenylethylamine as substrate) in rat brain. The inhibition of type A MAO was accompanied by an increase in epinephrine concentration in hypothalamus. Although the absolute concentration of epinephrine in rat hypothalamus is low relative to norepinephrine and dopamine, the percentage increase in epinephrine after LY51641 was greater than the percentage increase in dopamine or norepinephrine. The inhibition of type A MAO activity and increase in hypothalamic epinephrine 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 epinephrine concentration. Two analogs of LY51641 of differing selectivity elevated epinephrine 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. These findings support earlier evidence that in rat hypothalamus, epinephrine oxidation occurs by type A not type B MAO.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000032:analysis* / Q000502:physiology; D006246:Harmaline / Q000494:pharmacology; D007031:Hypothalamus / Q000032:analysis; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology; D010293:Pargyline / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology; D051381:Rats
D003521:Cyclopropanes; D008996:Monoamine Oxidase Inhibitors; D010647:Phenyl Ethers; C000434:Lilly 51641; D010293:Pargyline; D006246:Harmaline; D004837:Epinephrine