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The Pharmaceutical Society of Korea (대한약학회)
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Inhibitory actions of the antidepressant/antipanic drug phenelzine on brain GABA transaminase

  • Yoo, Byung-Kwon (Department of Genetic Engineering, College of Natural Science, Hallym University) ;
  • Hong, Joung-Woo (Department of Genetic Engineering, College of Natural Science, Hallym University) ;
  • Suk, Jae-Wook (Department of Genetic Engineering, College of Natural Science, Hallym University) ;
  • Ahn, Jee-Yin (Department of Genetic Engineering, College of Natural Science, Hallym University) ;
  • Yoo, Jeong-Suk (Department of Genetic Engineering, College of Natural Science, Hallym University) ;
  • Lee, Kil-Soo (Department of Biology, College of Natural Sciences, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry, College of Medicine, University of Ulsan) ;
  • Choi, Soo-Young (Department of Genetic Engineering, College of Medicine, University of Ulsan)
  • Published : 1996.12.01
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Abstract

Brain GABA transaminase is inactivated by preincubation with antidepressant/antipanic drug pheneizine (${\beta}$ethylphenylhydrazine) (mixing molar ratio 10:1) at pH 7.4. The reaction of enzyme with phenelzine was monitored by absorption and fluorescence spectroscopic methods. The inactive enzyme was fully reconstituted by addition of cofactor pyridoxal-5-phosphate. This result implies that the blocking of 1 mol of pyridoxal-5-phosphate per enzyme dimer is needed for inactivation of the enzyme. The time course of the reaction is significantly affected by the substrate .alpha.-ketoglutarate, which afforded complete protection against the loss of catalytic activity. The kinetic studies shows that phenelzine reacts with the cofactor of enzyme with a second-order rate constant of $2.1{\times}10^3M^{-1}s^{-1}$. It is postulated that the antidepressant/antipanic drug phenelzine is able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on GABA degradative enzyme GABA transaminase.

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