Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase.
The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-14C]hydroxytryptamine binoxalate (100 microM) and beta-[ethyl-14C]phenylethylamine hydrochloride (20 microM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (Ki) of 12.5 microM and greater than 500 microM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10(-8) to 10(-6) M), more than 20% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.
Adem
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Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
Jossan
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Oreland
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D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000609:Aminoacridines / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013619:Tacrine / Q000494:pharmacology* / Q000627:therapeutic use
D000609:Aminoacridines; D008996:Monoamine Oxidase Inhibitors; D013619:Tacrine; D008995:Monoamine Oxidase