5-Hydroxyindoleacetic acid formation

HT reuptake into the presynaptic neuron. Inhibiting reuptake of 5-HT makes more 5-HT available to postsynaptic receptors and reduces formation of the 5-HT metabolite 5-hydroxyindoleacetic acid. Although other antidepressants, such as imipramine and amitriptyline, inhibit 5-HT reuptake, they are less potent and selective than the SSRIs and clomipramine. Prolonged exposure to increased amounts of 5-HT after chronic antidepressant treatment (2 to 3 weeks) leads to altered responsiveness of postsynaptic 5-HT receptors or presynaptic autoregulatory receptors that govern 5-HT release in specific brain regions. ... 

Most of the common amino acids and their peptides are not oxidisable at commonly used electrodes. The exceptions are the amino acids tryptophan, tyrosine and cysteine. The oxidation of tyrosine is analogous to that of the catechols shown above. In the case of tryptophan and its metabolites serotonin and 5-hydroxyindoleacetic acid, the electrochemistry involves the oxidation of the carbon at position 2 on the indole ring with the formation of oxyindolalanine (Figure 2.9). 

Considerable information about serotonin metabolism has been learned from the action of monoamine oxidase inhibitors. One of the first of these compounds to be discovered was l-isonicotinyl-2-isopropyl hydrazide (Marsilid) 376) Many other compounds have since been discovered that inhibit monoamine oxidase both in vHxo and in vivo 368). The outcome of the studies with monoamine oxidase inhibitors has been to show that when the enzyme is inhibited there is a diminished formation of 5-hydroxyindoleacetic acid and serotonin is converted to the 0-glucuronide and excreted in rodents. In man there is little formation of serotonin glucuro-nide. The fate of serotonin in man under these conditions is not known definitely, although serotonin-O-sulfate has been observed in carcinoid patients. Serotonin may also be methylated to yield W-methyl-serotonin 368). 

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