Editing Reserpine (section)

==History==
Reserpine was isolated in 1952 from the dried root of ''[[Rauvolfia serpentina]]'' (Indian snakeroot),<ref name="mercksource">[http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_r_03zPzhtm#1093125 Rauwolfia] Dorlands Medical Dictionary. Merck Source. 2002.</ref> which had been known as ''Sarpagandha'' and had been used for centuries in India for the treatment of insanity, as well as fever and snakebites<ref name="Columbia">{{cite encyclopedia | title = Reserpine | url = http://www.bartleby.com/65/re/reserpin.html | archive-url = https://web.archive.org/web/20090212221725/http://www.bartleby.com/65/re/reserpin.html | archive-date=2009-02-12 | encyclopedia = The Columbia Encyclopedia | edition = Sixth | date = 2005 | publisher = Columbia University Press }}</ref>&nbsp;— [[Mahatma Gandhi]] used it as a [[tranquilizer]].<ref>[https://web.archive.org/web/20080627161307/http://www.time.com/time/magazine/article/0,9171,857672,00.html Pills for Mental Illness?], ''[[TIME Magazine]]'', November 8, 1954</ref> It was first used in the United States by [[Robert Wallace Wilkins]] in 1950.  Its molecular structure was elucidated in 1953 and natural [[Cis-trans isomerism|configuration]] published in 1955.<ref name="Nicolaou">{{cite book |title= Classics in Total Synthesis| vauthors = Nicolaou KC, Sorensen EJ | author-link1 = K. C. Nicolaou  |year= 1996|publisher= VCH|location= Weinheim, Germany|isbn= 978-3-527-29284-4|page= [https://archive.org/details/classicstotalmet00kcni_087/page/n80 55] |url=https://archive.org/details/classicstotalmet00kcni_087|url-access= limited}}</ref> It was introduced in 1954, two years after [[chlorpromazine]].<ref name="history1">{{cite journal | vauthors = López-Muñoz F, Bhatara VS, Alamo C, Cuenca E | title = [Historical approach to reserpine discovery and its introduction in psychiatry] | journal = Actas Españolas de Psiquiatría | volume = 32 | issue = 6 | pages = 387–95 | year = 2004 | pmid = 15529229 | url = http://www.arsxxi.com/Revistas/mostrararticulo.php?idarticulo=411106110 }}</ref> The first [[total synthesis]] was accomplished by [[R. B. Woodward]] in 1958.<ref name="Nicolaou"/>

Reserpine was influential in promoting the thought of a [[biogenic amine]] hypothesis of depression.<ref>{{cite journal | vauthors = Everett GM, Toman JE | date =1959 | title = Mode of action of Rauwolfia alkaloids and motor activity | journal = Biol Psychiat | volume = 2 | pages = 75–81 }}</ref><ref>{{cite book | vauthors = Govindarajulu M | veditors = Agrawal D | title = Medicinal herbs and fungi : neurotoxicity vs. neuroprotection | publisher = Springer | location = Singapore | year = 2021 |chapter=Reserpine-Induced Depression and Other Neurotoxicity: A Monoaminergic Hypothesis. | isbn = 978-981-334-140-1 }}</ref> Reserpine-induced depletion of monoamine [[neurotransmitter]]s in the [[synapse]] allegedly caused depression and was cited as evidence that a "chemical imbalance", namely low levels of monoamine neurotransmitters, is what causes [[clinical depression]] in humans. A 2003 review showed barely any evidence that reserpine actually causes depression in either human patients or animal models.<ref>{{cite journal | vauthors = Baumeister AA, Hawkins MF, Uzelac SM | title = The myth of reserpine-induced depression: role in the historical development of the monoamine hypothesis | journal = Journal of the History of the Neurosciences | volume = 12 | issue = 2 | pages = 207–20 | date = June 2003 | pmid = 12953623 | doi = 10.1076/jhin.12.2.207.15535 | s2cid = 42407412 }}</ref> Notably, reserpine was the first compound ever to be shown to be an effective antidepressant in a randomized placebo-controlled trial.<ref>{{cite journal | vauthors = Davies DL, Shepherd M | title = Reserpine in the treatment of anxious and depressed patients | journal = Lancet | volume = 269 | issue = 6881 | pages = 117–20 | date = July 1955 | pmid = 14392947 | doi = 10.1016/s0140-6736(55)92118-8 }}</ref><ref>{{cite book | author=Healy, David|title=The Antidepressant Era|publisher=Harvard University Press|year=1997|isbn=978-0-674-03958-2}}</ref> A 2022 [[systematic review]] found that studies of the influence of reserpine on mood were highly inconsistent, with similar proportions of studies reporting depressogenic effects, no influence on mood, and antidepressant effects.<ref name="pmid36000248">{{cite journal | vauthors = Strawbridge R, Javed RR, Cave J, Jauhar S, Young AH | title = The effects of reserpine on depression: A systematic review | journal = J Psychopharmacol | volume = 37| issue = 3| pages = 248–260 | date = August 2022 | pmid = 36000248 | doi = 10.1177/02698811221115762 | s2cid = 251765916 | url = | pmc = 10076328 }}</ref> The [[quality of evidence]] was limited, and only a subset of studies were [[randomized controlled trial]]s.<ref name="pmid36000248" /> Although reserpine itself cannot provide good evidence for the [[monoamine hypothesis]] of depression, other lines of evidence support the idea that boosting serotonin or norepinephrine can effectively treat depression, as shown by [[SSRI]]s, [[SNRI]]s, and [[tricyclic antidepressants]].