Ihibition of rat brain norepinephrine N-methyltransferase in vitro and in vivo by chloro-substituted 1-aminoindans.
Norepinephrine N-methyltransferase from rat brain stem was inhibited in vitro by 1-aminoindans with chlorine substituents on the aromatic ring. The order of inhibitory potency among these compounds was 4.5-dichloro greater than 4-chloro greater than 5-chloro approximately or equal to 5,6-dichloro approximately or equal to 6,7-dichloro greater than 6-chloro greater than 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 value determined from a Dixon plot was 3.3 x 10(-7) M. At doses of 10-40 mg/kg i.p., this compound inhibited brain stem and hypothalamic norepinephrine N-methyltransferase in vitro and lowered hypothalamic concentrations of epinephrine in rats, effects that lasted for several hours. 4,5-Dichloro-1-aminoindan may be a useful pharmacologic tool for studies of epinephrine-forming neurons in brain.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D004837:Epinephrine / Q000378:metabolism; D007031:Hypothalamus / Q000201:enzymology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D051381:Rats
D007189:Indans; D007192:Indenes; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine