Contribution of monoamine oxidase (MAO) to the binding of tertiary basic drugs in lung mitochondria.
The effects of tertiary amine-containing basic drugs on the enzymes located in the mitochondria and the effect of monoamine oxidase inhibitors (MAOIs) on drug accumulation in lung mitochondria have been studied. Various basic drugs inhibited MAO activity but not other mitochondrial marker enzymes. The potency of MAO inhibition correlated well with their lipid solubility, and the basic drugs inhibited MAO activity dose dependently and competitively. Further, MAO inhibition correlated well with binding affinity to lung mitochondria, and the binding of tertiary amine drugs to lung mitochondria was decreased by treatment with MAOIs. A good correlation was observed between the potency of MAOIs to inhibit the binding of the basic drug to the high-affinity site in mitochondria and the MAO inhibitory activity in mitochondria. These results indicate that mitochondrial MAO is one of the binding sites for tertiary basic drugs in the lung. We think that the action and/or adverse reaction of some drugs may result from inhibition of mitochondrial MAO to metabolize various biogenic amines and that mitochondrial MAO may function as a reservoir for basic drugs.
Yoshida
H
H
Department of Transfusion Medicine, Faculty of Medicine, Kyoto University, Japan.
Kamiya
A
A
Okumura
K
K
Hori
R
R
D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D008996:Monoamine Oxidase Inhibitors; D004364:Pharmaceutical Preparations; D008995:Monoamine Oxidase