Recent studies on the MAO inhibitor phenelzine and its possible metabolites

Summary

Although N²-acetylphenelzine (N²AcPLZ) appears to be only a minor metabolite of phenelzine (PLZ), other investigations have demonstrated that it may be worthy of study as an antidepressant in its own right. In the present report, the possibility of ring hydroxylation as a metabolic route for PLZ was investigated in the rat. Indirect evidence for such a route was obtained using iprindole, a drug known to block ring hydroxylation. Treatment of rats with iprindole followed by PLZ was demonstrated to result in increased brain levels of PLZ and β-phenylethylamine (control rats were treated with vehicle and then PLZ). The possibility that hydroxylation in the para-position might be a metabolic route for PLZ has led to interest in the possible use of analogues in which this position is blocked with a substituent. In preliminary acute studies at a dose of 0.1 mmol/kg p-chloro-PLZ was found to have a similar effect to PLZ on the inhibition of MAO and to lead to an elevation of catecholamines and 5-hydroxytryptamine (5-HT) in rat whole brain.