INHIBITORY ACTIONS OF THE ANTIDEPRESSANT ANTIPANIC DRUG PHENELZINE ONBRAIN GABA TRANSAMINASE/

Brain GABA transaminase is inactivated by preincubation with antidepre ssant/antipanic drug phenelzine (beta-ethylphenylhydrazine) (mixing mo lar ratio 10:1) at pH 7.4. The reaction of enzyme with phenelzine was monitored by absorption and fluorescence spectroscopic methods. The in active enzyme was fully reconstituted by addition of cofactor pyridoxa l-5-phosphate. This result implies that the blocking of 1 mot of pyrid oxal-5-phosphate per enzyme dimer is needed for inactivation of the en zyme. The time course of the reaction is significantly affected by:the substrate cc-ketoglutarate, which afforded complete protection agains t the loss of catalytic activity. The kinetic studies shows that phene lzine reacts with the cofactor of enzyme with a second-order rate cons tant of 2.1x10(3) M(-1)s(-1). If is postulated that the antidepressant /antipanic drug phenelzine is able to elevate the neurotransmitter GAB A levels in central nervous system by inhibitory action on GABA degrad ative enzyme GABA transaminase.