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

Brain GABA transaminase is inactivated by preincubation with antidepressant/antipanic drug phenelzine (β-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 α-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 × 10³ M^-1s^-1. It is postulated that the antidepressanl/antipanic drug phenelzine is able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on GABA degradative enzyme GABA transaminase.