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Biochemical Strategies for the Development of Antidepressants

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  • Pharmacology and Pathophysiology
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Summary

Evidence is available regarding the relationship between the specificity of antidepressants in modulating neurotransmitter systems and their therapeutic activity. All antidepressant treatments initiate adaptive changes in central serotonin (5-hydroxytryptamine; 5-HT) neurotransmission. This involves a desensitisation of postsynaptic serotonergic 5-HT1A receptors and an enhanced responsiveness of 5-HT2 receptors that are located postsynaptically. Antidepressants also induce changes in central noradrenergic transmission. This effect possibly arises as a consequence of alteration in serotonin heteroceptors that are located on noradrenergic terminals.

There are several different classes of antidepressants available at present that modulate biogenic amine neurotransmitters, e.g. reversible monoamine oxidase A inhibitors, selective serotonin reuptake inhibitors, α2-adrenoceptor antagonists, atypical benzodiazepines and 5-HT1A partial agonists.

The next generation of antidepressant drugs may be developed based on their ability to modify signal transductors (G proteins), or possibly to act at sites distal to receptors, such as second messenger complexes.

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    B. E. Leonard

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Leonard, B.E. Biochemical Strategies for the Development of Antidepressants. CNS Drugs 1, 285–304 (1994). https://doi.org/10.2165/00023210-199401040-00006

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