Direct and Indirect Effects of MAO Inhibitors and Trace Amines on Serotonergic Neurotransmission

Abstract

According to the “dopamine hypothesis of schizophrenia” an increase of dopamine (DA), especially in the mesolimbic system, plays an important role in the pathogenesis of this central disorder (Ackenheil et al., 1978). Since increased DA levels might reflect a deficiency of MAO [monoamine: O₂ oxidoreductase, deaminating (EC 1.4.3.4)] besides DA also the concentrations of other endogenous and exogenous amines could be enhanced in schizophrenia. On the basis of the assumption that decreased MAO activity reflects a genetic defect, the activity of this enzyme should be affected not only in the brain but also in other tissues. As a peripheral marker of synaptic function and metabolism, blood platelets are frequently used. Many studies were published on the MAO activity in platelets of patients with schizophrenia using different substrates. The results obtained are disappointing and controversial: if MAO deficiency plays a role in the pathogenesis of this disease then probably only in different subtypes of chronic schizophrenia. — Besides the “DA hypothesis” O- and N-methylated derivatives of DA and serotonin (5-HT) are discussed as a biochemical basis of schizophrenia (“transmethylation hypothesis”), since some of these derivatives induce experimental psychosis (Krüger, 1981).