The compounds that are called tricyclic antidepressants (doxepin hydrochloride, amitriptyline hydrochloride, imipramine hydrochloride, trimipramine maleate, nortriptyline hydrochloride, protriptyline hydrochloride, and desipramine hydrochloride) were discovered to have antidepressant efficacy beginning in the 1950s, shortly after
chlorpromazine hydrochloride was found to be effective for treating psychoses. Researchers took compounds from the shelves of pharmaceutical houses that were similar to chlorpromazine in structure and pharmacology to look for other agents for the treatment of psychoses. The antihistamine imipramine was the first drug in this group to be shown to be effective as an antidepressant after it failed to demonstrate antipsychotic efficacy.1
Soon after the tricyclic antidepressants became available for use clinically, it was learned that these compounds were potent inhibitors of the presynaptic uptake of norepinephrine and serotonin. These early findings represent some of the cornerstones of the biogenic amine hypothesis of mood disorders. More recently, we have learned about the effects
Richelson E. Tricyclic Antidepressants: Drugs for Other Diseases. Arch Intern Med. 1982;142(2):231–232. doi:10.1001/archinte.1982.00340150031005
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