Tranylcypromine sulfate, (±)-trans-2-phenylcyclopropylaminesulfate (Parnate), was synthesized to be an amphetamineanalog (visualize the α-methyl of amphetaminecondensed onto the β-carbon atom).It does have someamphetamine-like properties, which may be why it has moreimmediate CNS-stimulant effects than agents that act byMAO inhibition alone. For MAO inhibition, there may betwo components to the action of this agent. One is thoughtto arise because tranylcypromine has structural features (thebasic nitrogen and the quasi-π character of the α- andβ-cyclopropane carbon atoms) that approximate the transitionstate in a route of metabolism of β-arylamines. As α-and β-hydrogen atoms are removed from the normal substrateof the enzyme, the quasi-π character develops over theα,β-carbon system. Duplication of the transition state permitsextremely strong, but reversible, attachment to the enzyme.Additionally, tranylcypromine is a mechanism-based inactivator.It is metabolized by MAO, with one electron of the nitrogenpair lost to flavin. This, in turn, produces homolyticfission of a carbon–carbon bond of cyclopropane, with oneelectron from the fission pairing with the remaining lone nitrogenelectron to generate an imine (protonated) and with theother residing on a methylene carbon. Thus, a free radical isformed that reacts to form a covalent bond with the enzymeor with reduced flavin to inactivate the enzyme.
