Editing Anxiolytic (section)

== History ==
The first monoamine oxidase inhibitor (MAOI), [[iproniazid]], was discovered accidentally when developing the new [[Tuberculosis management|antitubercular]] drug [[isoniazid]]. The drug was found to induce euphoria and improve the patient's appetite and sleep quality.<ref>{{Cite journal |last1=Van Der Walt |first1=Martie |last2=Keddy |first2=Karen H. |date=2021-06-01 |title=The Tuberculosis-Depression Syndemic and Evolution of Pharmaceutical Therapeutics: From Ancient Times to the Future |journal=Frontiers in Psychiatry |volume=12 |pages=617751 |doi=10.3389/fpsyt.2021.617751 |doi-access=free |issn=1664-0640 |pmc=8203803 |pmid=34140898}}</ref>

The first tricyclic antidepressant, [[imipramine]], was originally developed and studied to be an [[antihistamine]] alongside other first-generation antihistamines of the time, such as [[promethazine]].<ref name="Hillhouse">{{Cite journal |last1=Hillhouse |first1=Todd M. |last2=Porter |first2=Joseph H. |title=A brief history of the development of antidepressant drugs: From monoamines to glutamate. |url=http://dx.doi.org/10.1037/a0038550 |journal=Experimental and Clinical Psychopharmacology |year=2015 |volume=23 |issue=1 |pages=1–21 |doi=10.1037/a0038550 |pmid=25643025 |pmc=4428540 |issn=1936-2293}}</ref> TCAs can increase the level of norepinephrine and serotonin by inhibiting their reuptake transport proteins.<ref>{{Citation |last1=Moraczewski |first1=Jordan |title=Tricyclic Antidepressants |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK557791/ |work=StatPearls |access-date=2024-01-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491723 |last2=Awosika |first2=Ayoola O. |last3=Aedma |first3=Kapil K.}}</ref> The majority of TCAs exert greater effect on norepinephrine, which leads to side effects like drowsiness and memory loss. {{citation needed|date=January 2024}}

In order to be more effective on serotonin agonism and avoid anticholinergic and antihistaminergic side effects, selective serotonin reuptake inhibitors (SSRI) were researched and introduced to treat anxiety disorders. The first SSRI, [[fluoxetine]] (Prozac), was discovered in 1974 and approved by FDA in 1987. After that, other SSRIs like [[sertraline]] (Zoloft), [[paroxetine]] (Paxil), and [[escitalopram]] (Lexapro) have entered the market.<ref name="Hillhouse" />

The first serotonin norepinephrine reuptake inhibitor (SNRI), [[venlafaxine]] (Effexor), entered the market in 1993.<ref name="Hillhouse" /> SNRIs can target serotonin and norepinephrine transporters while avoiding imposing significant effects on other adrenergic (α<sub>1</sub>, α<sub>2</sub>, and β), histamine (H<sub>1</sub>), [[Muscarinic acetylcholine receptor|muscarinic]], dopamine, or postsynaptic serotonin receptors.<ref>{{Citation |last=Chu |first=Andrew |title=Selective Serotonin Reuptake Inhibitors |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK554406/ |access-date=2025-04-22 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119293 |last2=Wadhwa |first2=Roopma}}</ref>