Йохимбин: Химический состав, свойства и применение

the chemical compound
Chemical compound

Yohimbine (/j//oU//'//h//I//m//b//i://n/), 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. 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as a treatment for erectile dysfunction, although its reported clinical benefits were modest and it has largely been superseded by the PDE5 inhibitor class of drugs.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.

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.

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". 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; 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. 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.

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 target Binding affinity(Ki in nanomolar) 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 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

Yohimbine has been studied as a way to improve the effects of exposure therapy in people with post traumatic stress disorder (PTSD). It has also been studied as a potential treatment for erectile dysfunction but there is insufficient evidence to rate its effectiveness. 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. Nevertheless, the quantity of yohimbine in dietary supplements, often advertised as promoting sexual function, has been found to overlap with prescription doses of yohimbine. Yohimbine selectively blocks the pre synaptic α2 receptors. Blockade of post synaptic α2 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 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 receptors on the corpus cavernosum smooth muscle. Under physiologic conditions, however, nitric oxide attenuates norepinephrine vasoconstriction.

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. 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.

Aspidosperma quebracho blanco is an unrelated tree whose common name is quebracho blanco. It is found in large areas of central South America, particularly the Gran Chaco, where it is often the dominant species in the canopy. It is one of the most widely distributed Argentine arboreal species. Traditionally it was logged for fuel, timber and railway sleepers. 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. 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. This was disputed, and the matter long remained in doubt. 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:

A range of secondary reference works give 'quebrachine' as a synonym for yohimbine. 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. Rauvolfia, Amsonia, Vallesia and Vinca; from the family Loganiaceae (genera Gelsemium and Strychnos); and from the family Euphorbiaceae (genus Alchornea). However, WADA did not yet list Yohimbine (which can come into a body via an energy drink, also in a form of pre workout supplement or fat burner) 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.