Inhibitory actions of the antidepressant/antipanic drug phenelzine on brain GABA transaminase

• Published in: Archives of pharmacal research 1996, Vol.19 (6), p.480-485
• Main Authors: Yoo, Byung-Kwon, Hong, Joung-Woo, Suk, Jae-Wook, Ahn, Jee-Yin, Yoo, Jeong-Suk, Lee, Kil-Soo, Cho, Sung-Woo, Choi, Soo-Young
• Format: Article
• Language: Korean
• ISSN: 0253-6269; 1976-3786

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.