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Revision as of 16:26, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 470514738 of page Yohimbine for the Chem/Drugbox validation project (updated: '').  Latest revision as of 05:56, 20 December 2024 edit Ttocserp (talk | contribs)Extended confirmed users35,368 edits →Extracts and chemistry: Replacing dead link 
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{{Redirect|Yoman|the film called "Yoman" in Hebrew|Diary (1983 film)}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{About|the chemical compound|the plant and its medicinal bark preparation|yohimbe}}
{{Short description|Chemical compound}}
{{Drugbox {{Drugbox
| verifiedrevid = 470634701
| Verifiedfields = changed
| image = Yohimbine.png
| verifiedrevid = 440670147
| width =
| IUPAC_name = 17α-hydroxy-yohimban-16α-<br />carboxylic acid methyl ester
| image = Yohimbine structure.svg | image2 = Yohimbine-from-xtal-3D-bs-17.png
| width = 200 | width2 =


<!--Clinical data--> <!--Clinical data-->
| pregnancy_category =
| tradename = Yocon
| routes_of_administration = ]
| pregnancy_category =
| legal_status = OTC | ATC_prefix = G04
| ATC_suffix = BE04
| routes_of_administration = Oral
| ATC_supplemental = {{ATCvet|V03|AB93}}
| legal_AU = S4
| legal_CA = Rx-only
| legal_US = unscheduled
| legal_US_comment =


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability = 7-86% (mean 33%)
| metabolism = | metabolism =
| excretion = | excretion = Urine (as metabolites)
| elimination_half-life = 0.25-2.5 hours<ref>{{cite journal | vauthors = Hedner T, Edgar B, Edvinsson L, Hedner J, Persson B, Pettersson A | title = Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers | journal = European Journal of Clinical Pharmacology | volume = 43 | issue = 6 | pages = 651–6 | year = 1992 | pmid = 1493849 | doi = 10.1007/BF02284967 | s2cid = 12346330 }}</ref>


<!--Identifiers--> <!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 146-48-5 | CAS_number = 146-48-5
| ATC_prefix = G04
| ATC_suffix = BE04
| ATC_supplemental = {{ATCvet|V03|AB93}}
| PubChem = 8969 | PubChem = 8969
| IUPHAR_ligand = 102 | IUPHAR_ligand = 102
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01392 | DrugBank = DB01392
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2Y49VWD90Q | UNII = 2Y49VWD90Q
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10093 | ChEBI = 10093
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 15245 | ChEMBL = 15245
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08685
| synonyms =


<!--Chemical data--> <!--Chemical data-->
| IUPAC_name = 17α-hydroxyyohimban-16α-carboxylic acid methyl ester
| C=21 | H=26 | N=2 | O=3
| C=21 | H=26 | N=2 | O=3
| molecular_weight = 354.44 g/mol (base)<br />390.90 g/mol (hydrochloride)
| smiles = O=C(OC)54C3c2nc1ccccc1c2CCN3C4CC5O | SMILES = 15CC(O)(C(=O)OC)1()C4()c3c2ccccc2c3CCN4C5
| InChI = 1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15-,17-,18-,19+/m0/s1
| InChIKey = BLGXFZZNTVWLAY-SCYLSFHTSA-N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15-,17-,18-,19+/m0/s1 | StdInChI = 1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15-,17-,18-,19+/m0/s1
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| StdInChIKey = BLGXFZZNTVWLAY-SCYLSFHTSA-N | StdInChIKey = BLGXFZZNTVWLAY-SCYLSFHTSA-N
}} }}

'''Yohimbine''' ({{IPAc-en|j|oU|'|h|I|m|b|i:|n}}),<ref>{{cite web | title = Yohimbine. (n.d.) | work = Collins English Dictionary – Complete and Unabridged. (1991, 1994, 1998, 2000, 2003). | access-date = 27 January 2015 | url = http://www.thefreedictionary.com/yohimbine }}</ref> also known as '''quebrachine''', is an ] ] derived from the bark of the African tree '']''; also from the bark of the unrelated South American tree '']''. Yohimbine is an ], and has been used in a variety of research projects. It is a veterinary drug used to reverse sedation in dogs and deer.

While yohimbine behaves as an ] in some mammals, it does not do so in humans. It has been prescribed as a treatment for ], although its reported clinical benefits were modest and it has largely been superseded by the ] class of drugs. Substances that have purported to be extracts from the yohimbe tree have been marketed as dietary supplements for various purposes, but they contain highly variable amounts of yohimbine, if any; no published ] supports their efficacy.

==Uses==
Yohimbine is a drug used in veterinary medicine to reverse the effects of ] in dogs and deer.<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=522.2670 | title = 21 CFR Sec. 522.2670 Yohimbine }}</ref> It is used as a research reagent. In the US, it is prescribed, but now rarely, for erectile dysfunction in men.

==Yohimbine and yohimbe==
===Confusion===
Yohimbine should not be confused with ]<ref>{{cite book|title=Mosby's Dental Drug Reference - E-Book| veditors = Jeske AH |edition=11th |publisher=Elsevier Health Sciences|year=2013|isbn= 978-0323172264}}, Appendix H, e83;
</ref> but often is.<ref>{{cite book| vauthors = Holt S, Atkins RC, Krueger RJ, Sinatra ST, Taylor T |title=The sexual revolution: natural and healthy alternatives to sex|publisher=ProMotion Pub|year=1999|isbn=978-1579010409|page=105}}</ref>

Yohimbe is the common English name for the tree species ''P. johimbe'' (also called ''Corynanthe johimbe'')
and, by extension, the name of a medicinal preparation made from the bark of that tree, sold as an ].<ref>''Oxford English Dictionary Online'', article "Yohimbe", senses 1 and 2, respectively; ''Merriam-Webster Online'', article "Yohimbe", first and second senses, respectively.</ref> In contrast, yohimbine is a pure alkaloid that can be isolated from yohimbe bark.

Yohimbine is just one of at least 55 indole alkaloids that have been isolated from the bark;<ref>{{cite journal | vauthors = Sun J, Baker A, Chen P | title = Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry | journal = Rapid Communications in Mass Spectrometry | volume = 25 | issue = 18 | pages = 2591–602 | date = September 2011 | pmid = 23657953 | doi = 10.1002/rcm.5158 | bibcode = 2011RCMS...25.2591S }}</ref> and, while it has been described as the most active of these,<ref name = "Cohen_2015">{{cite journal | vauthors = Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA | title = Pharmaceutical quantities of yohimbine found in dietary supplements in the USA | journal = Drug Testing and Analysis | volume = 8 | issue = 3–4 | pages = 357–69 | year = 2015 | pmid = 26391406 | doi = 10.1002/dta.1849 | doi-access = free }}</ref> it constitutes only 15% of the total alkaloid content.<ref name = "Betz_2010">{{cite book | vauthors = Betz JM |chapter=Yohimbe | veditors = Coates PM, Betz JM, Blackman MR, Cragg GM, Levine M, Moss J, White JD |title=Encyclopedia of Dietary Supplements|url=https://archive.org/details/encyclopediadiet00pcoa |url-access=limited |publisher=Informa Healthcare|location=New York and London |pages=–3 |year=2010 |edition=2nd |isbn=9781439819289 }}</ref> Others include ], ] and ];<ref name = "Betz_2010" /> the bark also contains non-alkaloids about which virtually nothing is known.<ref name = "Betz_2010" />

Yohimbe, thus a complex mixture, has been studied far less thoroughly than yohimbine, the pure compound.<ref name = "Betz_2010" /> Pharmaceutical grade yohimbine is usually presented as the ],<ref name = "EFSA_2013">{{cite journal|title=Scientific Opinion on the evaluation of the safety in use of Yohimbe (Pausinystalia yohimbe (K. Schum.) Pierre ex Beille|last=EFSA Panel on Food Additives and Nutrient Sources Added to Food (ANS)|journal=EFSA Journal|volume=11|issue=7|year=2013|pages=1–46 | doi = 10.2903/j.efsa.2013.3302|doi-access=free}}</ref>{{rp|3,14,34}}<ref name = "Betz_2010" /> which is more soluble.

===Effect on sexual function===
====History, research and literature====
Yohimbe is used in folk medicine as an ]. In 1900, it attracted scientific interest in Germany, where an initial report claimed that yohimbe exerted a strong aphrodisiacal effect in animals and humans.<ref name = "Betz_2010" /> Attention soon shifted from the plant to its active constituents, particularly yohimbine.<ref name = "Betz_2010" /> According to a 2010 encyclopedia article by Joseph M. Betz<ref>Dr Betz was described as "a leading ''P. johimbe'' expert" by Cohen et al, 357. In 2018 he was appointed acting director of the Office of Dietary Supplements of the. NIH: {{cite web|url=https://ods.od.nih.gov/About/Joseph_Betz.aspx|access-date=28 January 2019|title=JOSEPH M. BETZ, PH.D., ACTING DIRECTOR, ODS|work=National Institutes of Health: Office of Dietary Supplements|archive-date=1 February 2019|archive-url=https://web.archive.org/web/20190201013503/https://ods.od.nih.gov/About/Joseph_Betz.aspx|url-status=dead}}</ref> of the ]:

{{quote|Probably as a result of this trend, no reports of human studies on the effects of crude yohimbe bark or its extracts on sexual performance can be found in the literature... Any discussion of the use of the bark for sexual enhancement thus begins and ends with folklore.}} In contrast, there is a "fairly rich literature on yohimbine".<ref name = "Betz_2010" />

Subsequent work on yohimbine, while confirming that it behaves as an aphrodisiac in animals, including rats, dogs and golden hamsters,<ref name = "Betz_2010" /> has failed to do so in humans. According to Betz:
{{quote|experiments show that the alkaloid increases sexual motivation even in sexually exhausted rats due to its action on the central α<sub>2</sub>-adrenoreceptors found in the ] in the brain. Blockage of these brain adrenoreceptors appears to reverse a central ] mechanism that regulates penile erection and maintains ]... the compound does not increase sexual desire and thoughts in human clinical trials. The combined evidence from human and animal clinical studies indicates that yohimbine is far less potent in stimulating sexual behavior in humans than in rats. One possible explanation for this finding is the existence of powerful and multiple inhibitory controls on sexual behavior in humans that are not present in rats i.e. the cognitive aspects of sex are far more important in humans than the basic instinctive functions observed in animals.<ref name = "Betz_2010" />|sign=|source=}}

====Clinical efficacy====
Yohimbine has been used to treat female sexual dysfunction, but there are few reported clinical trials and these do not show it to be better than placebo.<ref>Betz, 2010, 862.</ref> On treatment for male erectile dysfunction (ED), a review article by Tam ''et al.'' (2001) concluded:

{{quote|Although well-tolerated and safe, even when greatly exceeding the likely therapeutic range, it is obvious that the efficacy of as monotherapy in the general ED population is likely to be modest.<ref>{{cite journal | vauthors = Tam SW, Worcel M, Wyllie M |title=Yohimbine: a clinical review |journal=Pharmacology and Therapeutics |year=2001 |volume=91 |issue=3 |page =239 | doi = 10.1016/S0163-7258(01)00156-5 |pmid=11744068 }}</ref>}}

Again according to Betz (2010),

{{quote|The modern consensus appears to be that the pure compound yohimbine is effective for treating certain mild types of erectile dysfunction in some men, but does not act as an aphrodisiac".<ref name = "Betz_2010" />}}

A 2011 review by Andersson said:
{{quote|The effects of yohimbine have been investigated in several controlled trials on patients with different types of ED, but the effect has been modest... It cannot be excluded that orally administered yohimbine may have a beneficial effect in some patients with ED. However, as a consequence of the conflicting results, it is not currently recommended in most guidelines for management of ED.<ref>{{cite journal | vauthors = Andersson KE | title = Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction | journal = Pharmacological Reviews | volume = 63 | issue = 4 | pages = 811–59 | date = December 2011 | pmid = 21880989 | doi = 10.1124/pr.111.004515 | s2cid = 6146853 }}</ref>}}

Yohimbine has been largely superseded by the ] drugs such as ] (Viagra). Prescriptions for it are now rare, and most US pharmaceutical manufacturers have discontinued production of prescription capsules and tablets.<ref name="Cohen_2015" />{{rp|357–8}}

===Yohimbine and dietary supplements===

In the US, "yohimbe" preparations are sold as a dietary supplements for enhancing ], for weight loss and as aids for bodybuilding; but "There is virtually no published research on yohimbe which supports these or any other claims".<ref name = "Betz_2010" />{{rp|861}} Often, these products explicitly claim to contain yohim''bine''.<ref name="Cohen_2015" />

Cohen et al. found that samples of brands sold in American brick-and-mortar stores contained highly variable amounts of yohimbine, and sometimes none at all.<ref name="Cohen_2015" />{{rp|368}} Labelling claims were often misleading.<ref name = "Cohen_2015" />{{rp|368}} Similar results have been reported by other laboratories for products sold in the U.S., in other countries and on the internet.<ref>{{cite journal | vauthors = Betz JM, White KD, der Marderosian AH | title = Gas chromatographic determination of yohimbine in commercial yohimbe products | journal = Journal of AOAC International | volume = 78 | issue = 5 | pages = 1189–94 | year = 1995 | doi = 10.1093/jaoac/78.5.1189 | pmid = 7549534 | quote = Concentrations of yohimbine in the commercial products ranged from < 0.1 to 489 ppm, compared with 7089 ppm in the authentic bark. | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zanolari B, Ndjoko K, Ioset JR, Marston A, Hostettmann K | title = Qualitative and quantitative determination of yohimbine in authentic yohimbe bark and in commercial aphrodisiacs by HPLC-UV-API/ MS methods | journal = Phytochemical Analysis | volume = 14 | issue = 4 | pages = 193–201 | year = 2003 | pmid = 12892413 | doi = 10.1002/pca.699 | bibcode = 2003PChAn..14..193Z | quote = Twenty commercial aphrodisiac preparations were analysed and the amount of yohimbine measured and expressed as the maximal dose per day suggested on product labels ranged from 1.32 to 23.16 mg. }}</ref><ref>{{cite journal | vauthors = Raman V, Avula B, Galal AM, Wang YH, Khan IA | title = Microscopic and UPLC-UV-MS analyses of authentic and commercial yohimbe (Pausinystalia johimbe) bark samples | journal = Journal of Natural Medicines | volume = 67 | issue = 1 | pages = 42–50 | date = January 2013 | pmid = 22402817 | doi = 10.1007/s11418-012-0642-2 | s2cid = 11977944 | quote = Of 12 commercial samples tested, yohimbine was not detected in one; its presence in other samples was found to be in the range 0.1–0.91%.}}</ref><ref>{{cite journal | vauthors = Sun J, Chen P | title = Chromatographic fingerprint analysis of yohimbe bark and related dietary supplements using UHPLC/UV/MS | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 61 | pages = 142–9 | date = March 2012 | pmid = 22221902 | doi = 10.1016/j.jpba.2011.11.013 | quote = Wide variability was observed in fingerprints and yohimbine content among yohimbe dietary supplement samples. For most of the dietary supplements, the yohimbine content was not consistent with the label claims. }}</ref><ref>{{cite journal | vauthors = Badr JM | title = A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations | journal = Pharmacognosy Magazine | volume = 9 | issue = 33 | pages = 4–8 | date = January 2013 | pmid = 23661986 | pmc = 3647393 | doi = 10.4103/0973-1296.108124 | quote = Amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero to 1.5–1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. | doi-access = free }}</ref> One study found that many brands of "yohimbe" might not derive from the ''P. johimbe'' tree in the first place.<ref>Cohen et al, 368. (Samples did not include other alkaloids characteristic of ''P. yohimbe''.)</ref> According to yet another source, the yohimbe sold in markets in West Africa, where the tree grows, is frequently adulterated with other species of the genus ''Pausinystalia''; these contain little yohimbine.<ref name = "Jiofack_2012">{{cite book |chapter=Pausinystalia johimbe| vauthors = Jiofack Tafokou RB |pages=516–519 | volume = 7 | title = Timbers 2 of Plant Resources of Tropical Africa | veditors = Lemmens RH, Louppe D, Oteng-Amoako AA |publisher=PROTA Foundation |year=2012 |location=Wageningen, Ne |isbn=978-9290814955 }}</ref> The amounts of alkaloid found even in genuine ''P. johimbe'' bark vary considerably, depending on the source of the bark (roots, stem, branches, height, etc.).<ref>{{cite journal|title=Répartition des alcaloïdes dans le Yohimbe (Pausinystalia yohimbe) (K. Schum.) ex Pierre| vauthors = Paris R, Letouzey R |journal=Journal d'Agriculture Traditionnelle et de Botanique Appliquée |year=1960 |volume=7 |issue=4–5 |pages = 256–258 |language=fr | doi = 10.3406/jatba.1960.2608 }}</ref>

Some brands sold over-the-counter were found to contain more yohimbine per serving than a standard pharmaceutical dose;<ref name = "Cohen_2015" />{{rp|368}} yet, in the US, pharmaceuticals are subject to the strict regulatory regime pertaining to medicines. It is illegal to introduce or deliver "drugs" into interstate commerce without the permission of the ]. The FDA has asserted that some yohimbine-containing products are "drugs" because they are so promoted as to show "they are intended for use in the cure, mitigation, treatment or prevention of disease": 21 U.S.C. § 321(g)(1)(B).<ref>E.g. {{cite web|url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm402397|access-date=1 February 2019|title=Inspections, Compliance, Enforcement, and Criminal Investigations|publisher=US Food and Drug Administratiom}}</ref> However the legal position is not entirely straightforward,<ref>{{cite web|title=21 U.S. Code § 321 - Definitions; generally|work=Legal Information Institute|publisher=Cornell Law School|url=https://www.law.cornell.edu/uscode/text/21/321|access-date=1 February 2019}}</ref> and as of 1 February 2019 there does not appear to be any record of a successful prosecution.

Because of the lack of reliable scientific data on yohimbe, the European Food Safety Authority Panel on Food Additives determined that it was not possible to conclude on its safety or to establish a health-based guidance value.<ref name = "EFSA_2013" />{{rp|38}} They wrote:
{{quote|Overall the missing information include quantitative data on the composition and specifications of yohimbe bark and its preparations used in food and food supplements covering other alkaloids besides yohimbine, data on the bioavailability of active ingredients from the yohimbe bark extract and data on the toxicity of well specified individual preparations of yohimbe bark and the major yohimbe bark alkaloids, especially regarding subchronic toxicity, genotoxicity and reproductive toxicity.}}

==Extracts and chemistry==
Yohimbe ('']'') is a tree that grows in western and central ];<ref name="princessleia">{{cite web | url = http://apps.kew.org/wcsp/namedetail.do?name_id=148191 | work = Kew World Checklist of Selected Plant Families | title = Pausinystalia johimbe }}</ref> yohimbine was named as originally extracted from the bark of yohimbe in 1896 by Adolph Spiegel<ref>{{cite book |title=Year Book of the American Pharmaceutical Association |publisher=American Pharmaceutical Association |url=https://babel.hathitrust.org/cgi/pt?id=chi.095495193&seq=632|page=564 |year=1914 |access-date=20 December 2024}}</ref> (but see ] below). In 1943 the correct constitution of yohimbine was proposed by Witkop.<ref name="Witkop1943">{{cite journal | vauthors = Witkop B |title=Zur Konstitution des Yohimbins und seiner Abbauprodukte | trans-title = On the constitution of yohimbine and its breakdown products | language = de |journal=Justus Liebig's Annalen der Chemie |volume=554 |issue=1 |year=1943 |pages=83–126 |doi=10.1002/jlac.19435540108 }}</ref> Fifteen years later, a team led by ] used a 23-step synthesis to become the first persons to achieve the synthesis of yohimbine.<ref>{{cite book|title=The Alkaloids: Chemistry and Pharmacology | volume = 32 |date=1988|publisher=Academic Press|isbn=978-0-12-469532-0|page=564}}</ref><ref>{{cite journal | vauthors = van Tamelen E, Shamma M, Burgstahler A, Tamm R, Aldrich P |journal=] |title=The Total Synthesis of Yohimbine |year=1958 |volume=80|issue=18|pages=5006–5007 |doi=10.1021/ja01551a062|bibcode=1958JAChS..80.5006V }}</ref><ref>{{cite journal | vauthors = Herlé B, Wanner MJ, van Maarseveen JH, Hiemstra H | title = Total synthesis of (+)-yohimbine via an enantioselective organocatalytic Pictet-Spengler reaction | journal = The Journal of Organic Chemistry | volume = 76 | issue = 21 | pages = 8907–12 | date = November 2011 | pmid = 21950549 | doi = 10.1021/jo201657n }}</ref>

==Side effects==
]s of yohimbine in humans at high doses include increased ], ] (high blood pressure), ] (rapid heart rate), ], ], ], and ].<ref name="TamWorcelWyllie2001">{{cite journal | vauthors = Tam SW, Worcel M, Wyllie M | title = Yohimbine: a clinical review | journal = Pharmacol Ther | volume = 91 | issue = 3 | pages = 215–243 | date = September 2001 | pmid = 11744068 | doi = 10.1016/s0163-7258(01)00156-5 | url = }}</ref><ref name="BiaggioniRobertson1994">{{cite journal | vauthors = Biaggioni I, Robertson RM, Robertson D | title = Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure | journal = J Clin Pharmacol | volume = 34 | issue = 5 | pages = 418–423 | date = May 1994 | pmid = 8089252 | doi = 10.1002/j.1552-4604.1994.tb04981.x | url = }}</ref><ref name="CimolaiCimolai2011">{{cite journal | vauthors = Cimolai N, Cimolai T | title = Yohimbine use for physical enhancement and its potential toxicity | journal = J Diet Suppl | volume = 8 | issue = 4 | pages = 346–354 | date = December 2011 | pmid = 22432773 | doi = 10.3109/19390211.2011.615806 | url = }}</ref>

== Pharmacology ==
Yohimbine has high ] for the ], moderate affinity for the ], ], ], ], ], ], and dopamine ]s, and weak affinity for the ], ], ], ], and dopamine ]s.<ref name="pmid10611634">{{cite journal | vauthors = Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Cogé F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A | display-authors = 6 | title = Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states | journal = Synapse | volume = 35 | issue = 2 | pages = 79–95 | date = February 2000 | pmid = 10611634 | doi = 10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X | s2cid = 20221398 }}</ref><ref name="urlPDSP Ki Database">{{cite web | url = https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Yohimbine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | title = Yohimbine Test Ligand Search | work = PDSP Ki Database}}</ref> It behaves as an ] at α<sub>1</sub>-adrenergic, α<sub>2</sub>-adrenergic, 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and dopamine D<sub>2</sub>, and as a ] at 5-HT<sub>1A</sub>.<ref name="pmid10611634"/><ref name="pmid8517875">{{cite journal | vauthors = Arthur JM, Casañas SJ, Raymond JR | title = Partial agonist properties of rauwolscine and yohimbine for the inhibition of adenylyl cyclase by recombinant human 5-HT1A receptors | journal = Biochemical Pharmacology | volume = 45 | issue = 11 | pages = 2337–41 | date = June 1993 | pmid = 8517875 | doi = 10.1016/0006-2952(93)90208-E }}</ref><ref name="pmid6136920">{{cite journal | vauthors = Kaumann AJ | title = Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 323 | issue = 2 | pages = 149–54 | date = June 1983 | pmid = 6136920 | doi = 10.1007/BF00634263 | s2cid = 23251900 }}</ref><ref name="pmid8032658">{{cite journal | vauthors = Baxter GS, Murphy OE, Blackburn TP | title = Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle | journal = British Journal of Pharmacology | volume = 112 | issue = 1 | pages = 323–31 | date = May 1994 | pmid = 8032658 | pmc = 1910288 | doi = 10.1111/j.1476-5381.1994.tb13072.x }}</ref> Yohimbine interacts with serotonin and dopamine receptors in high concentrations.<ref>{{cite web|url=http://www.inchem.org/documents/pims/pharm/yohimbin.htm |title=Yohimbine (PIM 567) |publisher=Inchem.org |access-date=2013-05-26}}</ref>
{| class="wikitable sortable"
|+Pharmacologic profile
|-
! Molecular target !! ]<br />(K<sub>i</sub> in ])<ref name="urlPDSP Ki Database" /> !! Pharmacologic action<br /><ref name="pmid10611634"/><ref name="pmid8517875"/><ref name="pmid6136920"/><ref name="pmid8032658"/><ref>{{cite web|title=Yohimbine |url=http://www.drugbank.ca/drugs/DB01392 |website=DrugBank |publisher=University of Alberta |access-date=12 April 2014 |url-status=dead |archive-url=https://web.archive.org/web/20130130101146/http://www.drugbank.ca/drugs/DB01392 |archive-date=January 30, 2013 }}</ref><ref name="BenderParrLivingston2023">{{cite journal | vauthors = Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD | title = 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery | journal = J Med Chem | volume = 66 | issue = 16 | pages = 11027–11039 | date = August 2023 | pmid = 37584406 | pmc = 11073569 | doi = 10.1021/acs.jmedchem.3c01178 | url = }}</ref> !! Species !! Source
|-
| ] || 1,000 || Inhibitor || Human || Frontal cortex
|-
| ] || 346 || Partial agonist || Human || Cloned
|-
| ] || 19.9 || Antagonist || Human || Cloned
|-
| ] || 44.3 || Antagonist || Human || Cloned
|-
| ] || 1,264 || Unknown || Human || Cloned
|-
| ] || 91.6 || Unknown || Human || Cloned
|-
| ] || 1,822 || Antagonist || Human || Cloned
|-
| ] || 43–143.7 || Antagonist || Human || Cloned
|-
| ] || 2,850 || Unknown || Human || Cloned
|-
| ] || 1,680 || Antagonist || Human || Cloned
|-
| ] || 1,280 || Antagonist || Human || Cloned
|-
| ] || 770 || Antagonist || Human || Cloned
|-
| ] || 557 || Antagonist || Human || Cloned
|-
| ] || '''1.05''' || Antagonist || Human || Cloned
|-
| ] || '''1.19''' || Antagonist || Human || Cloned
|-
| ] || '''1.19''' || Antagonist || Human || Cloned
|-
| ] || 339 || Antagonist || Human || Cloned
|-
| ] || 3,235 || Antagonist|| Human || Cloned
|}

==Research==
Yohimbine has been studied as a way to improve the effects of ] in people with ] (PTSD).<ref>{{cite journal | vauthors = Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ | title = Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders | journal = Pharmacology & Therapeutics | volume = 149 | pages = 150–90 | date = May 2015 | pmid = 25550231 | pmc = 4380664 | doi = 10.1016/j.pharmthera.2014.12.004 | department = Review }}</ref><ref>{{cite journal | vauthors = McGuire JF, Lewin AB, Storch EA | title = Enhancing exposure therapy for anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder | journal = Expert Review of Neurotherapeutics | volume = 14 | issue = 8 | pages = 893–910 | date = August 2014 | pmid = 24972729 | pmc = 4125602 | doi = 10.1586/14737175.2014.934677 | department = Review }}</ref><ref>{{cite book | vauthors = van der Kolk BA |author-link= Bessel van der Kolk |chapter=The Treatment of Post Traumatic Stress Disorder |chapter-url=https://books.google.com/books?id=sVuMSVEY83UC&pg=PA421 | veditors = Hobfoll SE, De Vries MW |title=Extreme stress and communities: impact and intervention |publisher=Kluwer Academic Publishers |location=Boston |year=1995 |pages=421–44 |isbn=978-0-7923-3468-2}}</ref>

It has also been studied as a potential treatment for ] but there is insufficient evidence to rate its effectiveness.<ref name="MedlineSupplement">{{cite web| url=https://nccih.nih.gov/health/yohimbe |title=Yohimbe Supplement |date=February 2007 |publisher=National Center for Complementary and Integrative Health |access-date=2017-08-28}}</ref><ref name="Morales_2000">{{cite journal | vauthors = Morales A | title = Yohimbine in erectile dysfunction: the facts | journal = International Journal of Impotence Research | volume = 12 | issue = Suppl 1 | pages = S70–74 | date = March 2000 | pmid = 10845767 | doi = 10.1038/sj.ijir.3900508 | department = review | doi-access = free }}</ref><ref name=pharmrev>{{cite journal | vauthors = Andersson KE | title = Pharmacology of penile erection | journal = Pharmacological Reviews | volume = 53 | issue = 3 | pages = 417–50 | date = September 2001 | pmid = 11546836 | department = Review }}</ref> It is illegal in the United States to market an over the counter product containing yohimbine as a treatment for erectile dysfunction without getting FDA approval to do so.<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=310&showfr=1 | title = CFR - Code of Federal Regulations Title 21: Regulations on OTC products | publisher = U.S. Food and Drug Administration }}</ref> Nevertheless, the quantity of yohimbine in dietary supplements, often advertised as promoting sexual function, has been found to overlap with prescription doses of yohimbine.<ref name=DTA2016>{{cite journal | vauthors = Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA | title = Pharmaceutical quantities of yohimbine found in dietary supplements in the USA | journal = Drug Testing and Analysis | volume = 8 | issue = 3–4 | pages = 357–69 | date = March 2016 | pmid = 26391406 | doi = 10.1002/dta.1849 | department = primary | doi-access = free }}</ref>

Yohimbine selectively blocks the pre-synaptic ]. Blockade of post-synaptic α<sub>2</sub> receptors causes only minor ] ] relaxation, due to the fact that the majority of adrenoceptors in the corpus cavernosum are of the α<sub>1</sub> type. Blockade of pre-synaptic α<sub>2</sub> receptors facilitates the release of several neurotransmitters in the central and peripheral ] — thus in the corpus cavernosum — such as ] and ]. Whereas nitric oxide released in the corpus cavernosum is the major vasodilator contributing to the erectile process, norepinephrine is the major vasoconstrictor through stimulation of ] on the corpus cavernosum smooth muscle. Under physiologic conditions, however, nitric oxide attenuates norepinephrine vasoconstriction.<ref name="Pmid">{{cite journal | vauthors = Saenz de Tejada I, Kim NN, Goldstein I, Traish AM | title = Regulation of pre-synaptic alpha adrenergic activity in the corpus cavernosum | journal = International Journal of Impotence Research | volume = 12 | issue = Suppl 1 | pages = S20–25 | date = March 2000 | pmid = 10845761 | doi = 10.1038/sj.ijir.3900500 | department = Review | doi-access = free }}</ref>

==Botanical sources of yohimbine; sustainability==
===''Pausinystalia johimbe''===
The traditional source of yohimbine is the bark of the African tree ]. It has other uses, but the tree is sought out primarily for its bark; in practice, harvesting the bark kills the tree. Tree density is relatively low (average ≈ 4 harvestable trees/hectare). The high demand for medicines based on the bark has led to the tree's over-exploitation. The bark is traded in local markets and, because it is scarce, it is often adulterated with that of other species which contain little yohimbine.<ref name = "Jiofack_2012" /> The species is becoming endangered.<ref>{{cite book|chapter=Medicinal and aromatic plants in agroforestry systems| vauthors = Rao MR, Palada MC, Becker BN |title=New Vistas in Agroforestry: A Compendium for the 1st World Congress of Agroforestry, 2004| veditors = Nain PK, Rao MR, Buck LE |volume=1 |page=109 |publisher=Springer Science and Business Media |year=2013 |isbn=978-9401724241}}</ref>

Around the year 2000, ] was shipping ''P. johimbe'' to Europe at the rate of about 100 tonnes annually. Most bark is collected illegally by local people who are paid 150 ]s per kilo (about US$0.10 per pound) for delivery of pre-dried bark at the roadside. In practice they confuse and mix it with ''P. macroceras'' ("false yohimbe"), a species that contains little yohimbine.<ref>{{cite book|chapter=Yohimbe (‘’Pausinstalia johimbe’’)| vauthors = Sunderland TC, Ngo-Mpeck M, Tchoundjeu Z, Laird SA | pages =215–224|title=Tapping the Green Market: Certification & Management of Non-Timber Forest Products| veditors = Shanley P, Pierce AR, Laird SA, Guillén A |publisher=Earthscan Publications Ltd|year=2002|isbn= 978-1853838712 }}</ref>

===''Aspidosperma quebracho-blanco''===
'']'' is an unrelated tree whose common name is ''quebracho blanco''.<ref>"Quebracho" is formed from the Spanish words for "axe breaker'.</ref> It is found in large areas of central South America, particularly the ], where it is often the dominant species in the ].<ref>{{cite book|chapter=Chaco and Caatinga — South American Arid Savannas, Woodlands and Thickets| vauthors = Bucher EH |title=Ecology of Tropical Savannas|volume=42| series=Ecological Studies|pages=54–57| veditors = Huntley BJ, Walker BH |publisher=Springer Science and Business. Media|year=2012|isbn=978-3642687860}}</ref> It is one of the most widely distributed Argentine arboreal species.<ref>{{cite web|url=https://www.mendoza-conicet.gob.ar/ladyot/herba_digital/fichas_especies/quebracho_blanco.htm|access-date=12 January 2019|title=Nombre científico: Aspidosperma quebracho-blanco|language=es|publisher=CONICET|work=Herbario Digital}}</ref><ref name="Moglia_2001">{{cite journal|title=Variabilidad radial de algunos caracteres anatómicos de ''Aspidosperma'' quebracho blanco | trans-title = Radial variability of some anatomical characters of '' Aspidosperma '' white quebracho |journal=Bosque| vauthors = Moglia JG, López CR |volume=22 |issue=2 |year=2001 |issn=0304-8799 |page=4 |language=es |doi=10.4206/bosque.2001.v22n2-01 |doi-access=free }}</ref> Traditionally it was logged for fuel, timber and railway sleepers.<ref name="Moglia_2001" /> While in recent times cattle ranching and soya cultivation have led to considerable habitat loss,<ref>{{cite book| vauthors = Kent RB |title=Latin America: Regions and People|series=Texts in regional geography|page=151|publisher=Guilford Press|year=2006|isbn=978-1572309098}}</ref> and while there is still ], no shortage of the bark is reported. The tree has not been described as endangered: a few members of the genus ''Aspidosperma'' are on the ]. but the ''quebracho blanco'' species is not one of them.<ref>{{cite web|title=The IUCN Red List of Threatened Species|url=https://www.iucnredlist.org/search?query=aspidosperma&searchType=species|access-date=12 January 2019}}</ref>

In its bark an alkaloid is found which was given the name '''Quebrachine'''. In 1914, two scientific papers claimed quebrachine was chemically identical to yohimbine.<ref name="Yohimbine Quebrachine">{{cite journal| vauthors = Barger G, Field E |title=Yohimbine (Quebrachine)|journal=Journal of the Chemical Society, Transactions|year=1915|volume=107 |page=1025|doi=10.1039/CT9150701025|url=https://zenodo.org/record/1697152}}</ref> This was disputed,<ref>{{cite book|title=Allen's Commercial Organic Analysis| vauthors = Allen AH, Sadler SS, Lathrop EC, Mitchell CA |publisher=P. Blakiston's Son & Co.|year=1929|location=Philadelphia|page=217}}</ref> and the matter long remained in doubt.<ref>{{cite journal|title=Quebrachina y Yohimbina: Efectos Sobre la Corriente de Acción del Corazón| vauthors = Moyano Navarro B |journal=Revista de la Universidad Nacional de Córdoba|year=1942|language=es|pages=369–403}}. ('Quebrachine' and 'yohimbine' had different effects on the heart in the dog model; but the suppliers of those reagents were trusted to vouch for their authenticity.)</ref> However, in 1972, Effler and Effler using modern analytical techniques, including ], ], ], and ], established that quebrachine and yohimbine are one and the same thing. They wrote: {{quote|While it was almost unthinkable in 1914 ... that the same alkaloid was formed in different plants, recent studies have shown that this is certainly the case for indole alkaloids.<ref>{{cite journal| vauthors = Effler EH, Effler AH |title=Ûber die Identitat von Quebrachin und Yohimbin |journal=Chemischer Informationsdienst |year=1972 |volume=4 |issue=14 |language=de|pages=921–924}}</ref>}}

A range of secondary reference works give 'quebrachine' as a synonym for yohimbine.<ref>{{cite book|title=Adverse Effects of Herbal Drugs | vauthors = Abel G, Bos R, Bowen IH, Chandler RF, Corrigan D, Cubbin IJ, De Smet PA, Pras N, Scheffer JJ, Van Beek TT, Van Uden W, Woerdenbag HJ |volume=3|publisher=Springer Science & Business Media|year=2012|page=<!--ebook: no pagination.-->|isbn=978-3-642-60367-9 }}
</ref><ref>{{cite book|title=Emergency Medicine Therapeutics| vauthors = Bosker G | name-list-style = vanc |edition=2nd |publisher=Mosby, Incorporated|year=1995|isbn= 978-0815109921|page=342}}
</ref><ref>{{cite book|title=Elsevier's Dictionary of Vitamins and Pharmacochemistry| vauthors = Philippsborn H |page=599 | publisher=Elsevier |year=2006 |isbn=978-0080488790 }}
</ref><ref>{{cite book|title=Food and Drug Administration Consumer|author= Staff |publisher=U.S. Department of Health, Education, and Welfare, Public Health Service, Food and Drug Administration|year=1983|page=10}}
</ref><ref>{{cite book|title=Hawley's Condensed Chemical Dictionary | vauthors = Lewis RA, Hawley GG | veditors = Larrañaga MD, Lewis RJ, Lewis R |publisher=John Wiley & Sons|year=2016|page=1438|isbn= 978-1118135150}}
</ref><ref>{{cite book|title=Mosby's Dental Drug Reference - E-Book| veditors = Jeske AH |edition=11th |publisher=Elsevier Health Sciences|year=2013|isbn= 978-0323172264 | pages = Appendix H, e83}}
</ref><ref>{{cite book|title=The Alkaloids: Chemistry and Physiology|volume=8|page=696| vauthors = Manske RH, Meurant G |publisher=Academic Press|year=1965|isbn= 978-0080865324}}
</ref><ref>{{cite book|title=Veterinary Pharmacology and Therapeutics|page=353|edition=9th | veditors = Riviere JE, Papich MG |publisher=John Wiley & Sons|year=2013|isbn= 978-1118685907}}
</ref><ref>{{cite book|title=Encyclopedia of Common Natural Ingredients: Used in Food, Drugs, and Cosmetics|page=431| vauthors = Yeung AY, Foster S |edition=2nd |publisher=Wiley|year=2003|isbn=978-0471471288}}.
</ref>

Strictly speaking, wrote ], yohimbine should have been given the scientific name ''quebrachine'', seeing that it was first isolated from the quebracho tree and first named in the scientific literature. However the later work on ''P. yohimbe'' was better known, so the newer name stuck.<ref name="Yohimbine Quebrachine"/>

===Other plants===
Yohimbine has also been isolated from other plant genera in the family ] including ] (]),<ref name="pmid13373134">{{cite journal | vauthors = Hammouda Y, Janot MM, Le Men J | title = | language = fr | journal = Annales Pharmaceutiques Françaises | volume = 14 | issue = 5 | pages = 341–4 | date = May 1956 | pmid = 13373134 }}</ref> '']'', '']'', '']'' and '']''; from the family ] (genera '']'' and '']''); and from the family ] (genus '']'').<ref name = "Betz_2010" />

== Doping ==
There was a case in the ] practice in 2007, when an athlete, who reportedly consumed Yohimbine prior to a given athletic event, was later tested positive for ], which is a prohibited substance.<ref>See .</ref> However, WADA did not yet list Yohimbine (which can come into a body via an ],<ref>, p. 28.</ref> also in a form of ] or ]<ref></ref>) as a ], nor did it confirm that its use can increase the endogenous level of anabolic steroids, in particular of 19-norandrostenedione and testosterone.

== See also ==
* ]
* ]
* ]
* ]
* ]
* ]
* ]
* ]
* ]

== References ==
{{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/yohimbine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Yohimbine }}

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