[Biochemistry of depression and antidepressants]

Abstract

The pathways for the synthesis and degradation of the principal monoamines (dopamine, noradrenaline, serotonin, and phenylethylamine) concerned in the pathology of depression are briefly presented. Differences in the activities of the enzymes which control the amounts of monoamines or their principal metabolites in serum, urine or cerebrospinal fluid are discussed in relation to the different types of depression, as is also the role of changes in the sensitivity of neuronal receptors. The specific biochemical effects of monoamine oxidase inhibitors (MAOI's) and of the inhibitors of monoamine re-uptake are considered. MAOI's are classified as irreversible mixed inhibitors (A + B), as irreversible specific inhibitors and as reversible specific inhibitors; their mechanism of interaction with the enzyme is presented. Inhibitors of monamine re-uptake are classified according to their specificity for different monoamines. The mechanism of action of some antidepressants which have an atypical mechanism of action is outlined. Finally, the effect of chronic treatment with antidepressants on the sensitivities of the noradrenergic, serotoninergic and dopaminergic pre- and post-synaptic receptors is discussed.