Yohimbine

Yohimbine (Template:IPAc-en),<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> also known as quebrachine, is an indole alkaloid derived from the bark of the African tree Pausinystalia johimbe (yohimbe); also from the bark of the unrelated South American tree Aspidosperma quebracho-blanco. Yohimbine is an α₂-adrenergic receptor antagonist, 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 aphrodisiac in some mammals, it does not do so in humans. It has been prescribed as a treatment for erectile dysfunction, although its reported clinical benefits were modest and it has largely been superseded by the PDE5 inhibitor class of drugs.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 scientific evidence supports their efficacy.

Uses

Dietary supplementation

Yohimbe extracts, which contain yohimbine, have been used in traditional medicine and marketed as dietary supplements, mainly for its alleged benefits in the treatment of erectile dysfunction.<ref>Template:Cite journal</ref>

Erectile dysfunction

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><ref>Template:Cite journal</ref><ref name="Betz_2010" /><ref>Template:Cite journal</ref>

Yohimbine has been largely superseded by the PDE5 inhibitor drugs such as sildenafil (Viagra). Prescriptions for it are now rare, and most US pharmaceutical manufacturers have discontinued production of prescription capsules and tablets.<ref name="Cohen_2015" />Template:Rp

Yohimbe

Confusion

Yohimbine should not be confused with yohimbe<ref>Template:Cite book, Appendix H, e83; </ref> but often is.<ref>Template:Cite book</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 aphrodisiac.<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>Template:Cite journal</ref> and, while it has been described as the most active of these,<ref name = "Cohen_2015">Template:Cite journal</ref> it constitutes only 15% of the total alkaloid content.<ref name = "Betz_2010">Template:Cite book</ref> Others include rauwolscine, corynanthine and ajmalicine;<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 hydrochloride,<ref name = "EFSA_2013">Template:Cite journal</ref>Template:Rp<ref name = "Betz_2010" /> which is more soluble.

Effect on sexual function

Yohimbe is used in folk medicine as an aphrodisiac. 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" />

Yohimbe and dietary supplements

In the US, "yohimbe" preparations are sold as a dietary supplements for enhancing libido, 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" />Template:Rp Often, these products explicitly claim to contain yohimbine.<ref name="Cohen_2015" />

One study 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" />Template:Rp Labelling claims were often misleading.<ref name = "Cohen_2015" />Template:Rp Similar results have been reported by other laboratories for products sold in the US, in other countries and on the internet.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</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">Template:Cite book</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>Template:Cite journal</ref>

Some brands sold over-the-counter were found to contain more yohimbine per serving than a standard pharmaceutical dose;<ref name = "Cohen_2015" />Template:Rp 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 US Food and Drug Administration (FDA). 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. {{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead linkTemplate:Cbignore</ref> However the legal position is not entirely straightforward,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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" />Template:Rp They wrote: Template:Quote

Side effects

Side effects of yohimbine in humans at high doses include hypertension (high blood pressure), tachycardia (rapid heartbeat), agitation, hypervigilance, anxiety, tremors, nausea and urinary frequency.<ref name="TamWorcelWyllie2001">Template:Cite journal</ref><ref name="BiaggioniRobertson1994">Template:Cite journal</ref><ref name="CimolaiCimolai2011">Template:Cite journal</ref>

Pharmacology

Yohimbine has high affinity for the α₂-adrenergic receptor, moderate affinity for the α₁ receptor, 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1F, 5-HT_2B, and dopamine D₂ receptors, and weak affinity for the 5-HT_1E, 5-HT_2A, 5-HT_5A, 5-HT₇, and dopamine D₃ receptors.<ref name="pmid10611634">Template:Cite journal</ref><ref name="urlPDSP Ki Database">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It behaves as an antagonist at α₁-adrenergic, α₂-adrenergic, 5-HT_1B, 5-HT_1D, 5-HT_2A, 5-HT_2B, and dopamine D₂, and as a partial agonist at 5-HT_1A.<ref name="pmid10611634" /><ref name="pmid8517875">Template:Cite journal</ref><ref name="pmid6136920">Template:Cite journal</ref><ref name="pmid8032658">Template:Cite journal</ref> Yohimbine interacts with serotonin and dopamine receptors in high concentrations.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Pharmacologic profile

Molecular target	Binding affinity (Ki in nanomolar)<ref name="urlPDSP Ki Database" />	citation	CitationClass=web }}</ref><ref name="BenderParrLivingston2023">Template:Cite journal</ref> !! Species !! Source
SERT	1,000	Inhibitor	Human	Frontal cortex
5-HT1A	346	Partial agonist	Human	Cloned
5-HT1B	19.9	Antagonist	Human	Cloned
5-HT1D	44.3	Antagonist	Human	Cloned
5-HT1E	1,264	Unknown	Human	Cloned
5-HT1F	91.6	Unknown	Human	Cloned
5-HT2A	1,822	Antagonist	Human	Cloned
5-HT2B	43–143.7	Antagonist	Human	Cloned
5-HT7	2,850	Unknown	Human	Cloned
α1A	1,680	Antagonist	Human	Cloned
α1B	1,280	Antagonist	Human	Cloned
α1C	770	Antagonist	Human	Cloned
α1D	557	Antagonist	Human	Cloned
α2A	1.05	Antagonist	Human	Cloned
α2B	1.19	Antagonist	Human	Cloned
α2C	1.19	Antagonist	Human	Cloned
D2	339	Antagonist	Human	Cloned
D3	3,235	Antagonist	Human	Cloned

Extracts and chemistry

Yohimbe (Pausinystalia johimbe) is a tree that grows in western and central Africa;<ref name="princessleia">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> yohimbine was named as originally extracted from the bark of yohimbe in 1896 by Adolph Spiegel<ref>Template:Cite book</ref> (but see § Aspidosperma quebracho-blanco below). In 1943 the correct constitution of yohimbine was proposed by Witkop.<ref name="Witkop1943">Template:Cite journal</ref> Fifteen years later, a team led by Eugene van Tamelen used a 23-step synthesis to become the first persons to achieve the synthesis of yohimbine.<ref>Template:Cite book</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Research

Yohimbine has been studied as a way to improve the effects of exposure therapy in people with post-traumatic stress disorder (PTSD).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

Yohimbine selectively blocks the pre-synaptic α₂-adrenergic receptors. Blockade of post-synaptic α₂-adrenergic receptors causes only minor corpus cavernosum smooth muscle relaxation, due to the fact that the majority of adrenoceptors in the corpus cavernosum are of the α₁ type. Blockade of pre-synaptic α₂-adrenergic receptors facilitates the release of several neurotransmitters in the central and peripheral nervous system—thus in the corpus cavernosum—such as nitric oxide and norepinephrine. 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 α₁-adrenergic receptors on the corpus cavernosum smooth muscle. Under physiologic conditions, however, nitric oxide attenuates norepinephrine vasoconstriction.<ref name="Pmid">Template:Cite journal</ref>

It has also been studied as a potential treatment for erectile dysfunction, but there is insufficient evidence to rate its effectiveness.<ref name="MedlineSupplement">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Morales_2000">Template:Cite journal</ref><ref name="pharmrev">Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref>

Research 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 researcher Joseph M. Betz in a 2010 encyclopedia article:<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: {{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Veterinary use

Yohimbine is a drug used in veterinary medicine to reverse the effects of xylazine in dogs and deer.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Botanical sources

Pausinystalia johimbe

The traditional source of yohimbine is the bark of the African tree P. johimbe. 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>Template:Cite book</ref>

Around the year 2000, Cameroon 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 CFA francs 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>Template:Cite book</ref>

Aspidosperma quebracho-blanco

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 Gran Chaco, where it is often the dominant species in the canopy.<ref>Template:Cite book</ref> It is one of the most widely distributed Argentine arboreal species.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Moglia_2001">Template:Cite journal</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>Template:Cite book</ref> and while there is still illegal logging, 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 IUCN Red List. but the quebracho blanco species is not one of them.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref> This was disputed,<ref>Template:Cite book</ref> and the matter long remained in doubt.<ref>Template:Cite journal. ('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 mass spectrometry, UV absorption, IR absorption, and NMR, established that quebrachine and yohimbine are one and the same thing. They wrote: Template:Quote

A range of secondary reference works give 'quebrachine' as a synonym for yohimbine.<ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book </ref><ref>Template:Cite book. </ref>

Strictly speaking, wrote George Barger, 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 Apocynaceae including Lochnera (Catharanthus),<ref name="pmid13373134">Template:Cite journal</ref> Rauvolfia, Amsonia, Vallesia and Vinca; from the family Loganiaceae (genera Gelsemium and Strychnos); and from the family Euphorbiaceae (genus Alchornea).<ref name = "Betz_2010" />

Doping

There was a case in the World Anti-Doping Agency practice in 2007, when an athlete, who reportedly consumed Yohimbine prior to a given athletic event, was later tested positive for 19-norandrosterone, which is a prohibited substance.<ref>See the Mohadanni case.</ref> However, WADA did not yet list Yohimbine (which can come into a body via an energy drink,<ref>U.S. Anti-Doping Agency Supplement Guide, p. 28.</ref> also in a form of pre-workout supplement or fat burner<ref>Doping substances in dietary supplements</ref>) as a prohibited substance, nor did it confirm that its use can increase the endogenous level of anabolic steroids, in particular of 19-norandrostenedione and testosterone.

See also

• Ajmalicine
• Alstonine
• Corynanthine
• Deserpidine
• Mitragynine
• Rauwolscine
• Spegatrine
• Reserpine
• Rescinnamine

External links

• {{#invoke:citation/CS1|citation

|CitationClass=web }}

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