yohimbine yohimbine yohimbine (/joʊˈhɪmbiːn/), also known as quebrachine, is an indole alkaloid derived from the bark of the african tree pausinystalia johimbe; 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. this article is about the chemical compound. for the plant and its medicinal bark preparation, see yohimbe. yohimbineclinical dataroutes ofadministrationby mouthatc codeg04be04 (who) qv03ab93 (who)legal statuslegal status au: s4 (prescription only) ca: ℞-only us: otc pharmacokinetic databioavailability7-86% (mean 33%)elimination half-life0.25-2.5 hoursexcretionurine (as metabolites)identifiers iupac name 17α-hydroxyyohimban-16α-carboxylic acid methyl ester cas number146-48-5 ypubchem cid8969iuphar/bps102drugbankdb01392 ychemspider8622 yunii2y49vwd90qchebichebi:10093 ychemblchembl15245 ycomptox dashboard (epa)dtxsid9040130 echa infocard100.005.157 chemical and physical dataformulac21h26n2o3molar mass354.450 g·mol−13d model (jsmol)interactive image smiles 15cc(o)(c(=o)oc)1()c4()c3c2ccccc2c3ccn4c5 inchi 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 ykey:blgxfzzntvwlay-scylsfhtsa-n y (verify) 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as a treatment for erectile dysfunction, although its reported clinical benefits were modest and it has largely been superseded by the pde5 inhibitor class of drugs.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 yohimbine is a drug used in veterinary medicine to reverse the effects of xylazine in dogs and deer. 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 yohimbe but often is. 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. 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; and, while it has been described as the most active of these, it constitutes only 15% of the total alkaloid content. others include rauwolscine, corynanthine and ajmalicine; the bark also contains non-alkaloids about which virtually nothing is known. yohimbe, thus a complex mixture, has been studied far less thoroughly than yohimbine, the pure compound. pharmaceutical grade yohimbine is usually presented as the hydrochloride,: 3, 14, 34 which is more soluble. history, research and literature 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. attention soon shifted from the plant to its active constituents, particularly yohimbine. according to a 2010 encyclopedia article by joseph m. betz of the national institutes of health: 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". subsequent work on yohimbine, while confirming that it behaves as an aphrodisiac in animals, including rats, dogs and golden hamsters, has failed to do so in humans. according to betz: experiments show that the alkaloid increases sexual motivation even in sexually exhausted rats due to its action on the central α2-adrenoreceptors found in the locus coeruleus in the brain. blockage of these brain adrenoreceptors appears to reverse a central negative feedback mechanism that regulates penile erection and maintains detumescence... 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. 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. on treatment for male erectile dysfunction (ed), a review article by tam et al. (2001) concluded: 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. again according to betz (2010), 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". a 2011 review by andersson said: 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. 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.: 357–8 yohimbine has been found to be effective in treating delayed ejaculation in men yohimbine 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".: 861 often, these products explicitly claim to contain yohimbine. 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.: 368 labelling claims were often misleading.: 368 similar results have been reported by other laboratories for products sold in the u.s., in other countries and on the internet. one study found that many brands of "yohimbe" might not derive from the p. johimbe tree in the first place. 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. 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.). some brands sold over-the-counter were found to contain more yohimbine per serving than a standard pharmaceutical dose;: 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 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). however the legal position is not entirely straightforward, 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.: 38 they wrote: 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 (pausinystalia johimbe) is a tree that grows in western and central africa; yohimbine was named as originally extracted from the bark of yohimbe in 1896 by adolph spiegel (but see § aspidosperma quebracho-blanco below). in 1943 the correct constitution of yohimbine was proposed by witkop. 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. pharmacology yohimbine has high affinity for the α2-adrenergic receptor, moderate affinity for the α1 receptor, 5-ht1a, 5-ht1b, 5-ht1d, 5-ht1f, 5-ht2b, and dopamine d2 receptors, and weak affinity for the 5-ht1e, 5-ht2a, 5-ht5a, 5-ht7, and dopamine d3 receptors. it behaves as an antagonist at α1-adrenergic, α2-adrenergic, 5-ht1b, 5-ht1d, 5-ht2a, 5-ht2b, and dopamine d2, and as a partial agonist at 5-ht1a. yohimbine interacts with serotonin and dopamine receptors in high concentrations. pharmacologic profile molecular targetbinding affinity(ki in nanomolar)pharmacologic actionspeciessource sert1,000inhibitorhumanfrontal cortex 5-ht1a346partial agonisthumancloned 5-ht1b19.9antagonisthumancloned 5-ht1d44.3antagonisthumancloned 5-ht1e1,264unknownhumancloned 5-ht1f91.6unknownhumancloned 5-ht2a1,822antagonisthumancloned 5-ht2b143.7antagonisthumancloned 5-ht72,850unknownhumancloned α1a1,680antagonisthumancloned α1b1,280antagonisthumancloned α1c770antagonisthumancloned α1d557antagonisthumancloned α2a1.05antagonisthumancloned α2b1.19antagonisthumancloned α2c1.19antagonisthumancloned d2339antagonisthumancloned d33,235antagonisthumancloned research