Inhibition of brain mitochondrial monoamine oxidases by the endogenous compound 5-hydroxyoxindole.
5-Hydroxyoxindole is a recently identified endogenous compound. Its physiological role remains unclear but certain evidence exists, that it may share some regulatory properties with isatin, a known endogenous inhibitor of monoamine oxidase (MAO) type B (MAO-B). In this study several oxidized indoles were tested for their in vitro inhibition of MAO type A (MAO-A) and B of rat brain non-synaptic mitochondria. 5-Hydroxyoxindole was less potent MAO-A inhibitor (IC50 56.8 microM) than isatin (31.8 microM) and especially 5-hydroxyisatin (6.5 microM), but it was the only highly selective MAO-A inhibitor among the all compounds studied (IC50 MAO-A:IC50 MAO-B = 0.044). Thus, the in vitro data suggest that MAO-A may represent potential target for 5-hydroxyoxindole.
Crumeyrolle-Arias
Michèle
M
Laboratoire CRRET-FRE CNRS 2412, Université Paris 12 Val-de-Marne, 94010 Créteil, France. crumeyrolle@univ-paris12.fr
Tournaire
Marie-Claude
MC
Cane
Agnès
A
Launay
Jean-Marie
JM
Barritault
Denis
D
Medvedev
Alexei
A
D000818:Animals; D001921:Brain / Q000166:cytology; D007211:Indoles / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000078183:Oxindoles; D051381:Rats
C464901:5-hydroxyisatin; C484744:5-hydroxyoxindole; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D000078183:Oxindoles; D007510:Isatin; D008995:Monoamine Oxidase