INHIBITION OF RAT-BRAIN NOREPINEPHRINE NORMAL-METHYLTRANSFERASE INVITRO AND INVIVO BY CHLORO-SUBSTITUTED 1-AMINOINDANS

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 27  (3) , 485-495
Abstract
Norepinephrine N-methyltransferase from rat brain stem was inhibited in vitro by l-aminoindans with chlorine substituents on the aromatic ring. The order of inhibitory potency among these compounds was 4,5-dichloro > 4-chloro > 5-chloro .simeq. 5,6-dichloro .simeq. 6,7-dichloro > 6-chloro > 7-chloro. All except the 7-chloro compound were more potent inhibitors than the parent unsubstituted 1-aminoindan. 4,5-Dichloro-1-aminoindan was a competitive inhibitor in kinetic studies with L-norepinephrine as the variable substrate; its Ki [inhibition constant] value determined from a Dixon plot was 3.3 .times. 10-7 M. At doses of 10-40 mg/kg i.p., this compound inhibited brain stem and hypothalamic norepinephrine N-methyltransferase in vivo and lowered hypothalamic concentrations of epinephrine in rats, effects that lasted for several hours. 4,5-Dichloro-1-aminoindan may be a useful pharamacologic tool for studies of epinephrine-forming neurons in brain.