Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders.
Psoralen and isopsoralen, furocoumarins isolated from the plant Psoralea corylifolia L., were demonstrated to exhibit in vitro inhibitory actions on monoamine oxidase (MAO) activities in rat brain mitochondria, preferentially inhibiting MAO-A activity over MAO-B activity. This inhibition of enzyme activities was found to be dose-dependent and reversible. For MAO-A, the IC50 values are 15.2 +/- 1.3 microM psoralen and 9.0 +/- 0.6 microM isopsoralen. For MAO-B, the IC50 values are 61.8 +/- 4.3 microM psoralen and 12.8 +/- 0.5 microM isopsoralen. Lineweaver-Burk transformation of the inhibition data indicates that inhibition by both psoralen and isopsoralen is non-competitive for MAO-A. The Ki values were calculated to be 14.0 microM for psoralen and 6.5 microM for isopsoralen. On the other hand, inhibition by both psoralen and isopsoralen is competitive for MAO-B. The Ki values were calculated to be 58.1 microM for psoralen and 10.8 microM for isopsoralen. These inhibitory actions of psoralen and isopsoralen on rat brain mitochondrial MAO activities are discussed in relation to their toxicities and their potential applications to treat affective disorders.
Kong
L D
LD
State Key Laboratory of Pharmaceutical Biotechnology, Institute of Pharmaceutical Biology and Phytochemistry, Nanjing University, NT, Hong Kong, China.
Tan
R X
RX
Woo
A Y
AY
Cheng
C H
CH
D000341:Affective Disorders, Psychotic / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D005363:Ficusin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011564:Furocoumarins / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011564:Furocoumarins; D008996:Monoamine Oxidase Inhibitors; D010936:Plant Extracts; C011659:angelicin; D008995:Monoamine Oxidase; D005363:Ficusin