yohimbe general info

[MOUNTAIN-MAN]

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Yohimbine
Yohimbine structure.svg
Yohimbine3Dan.gif
Systematic (IUPAC) name
17α-hydroxy-yohimban-16α-
carboxylic acid methyl ester
Clinical data
Trade names Actibine, Erex, Testomar, Yocon, Yohimar, Yohimbe
Legal status Prescription Only (S4) (AU) OTC supplement (US)
Routes Oral
Pharmacokinetic data
Half-life 0.25-2.5 hours[1]
Excretion Urine (as metabolites)
Identifiers
CAS number 146-48-5 Yes
ATC code G04BE04 QV03AB93
PubChem CID 8969
IUPHAR ligand 102
DrugBank DB01392
ChemSpider 8622 Yes
UNII 2Y49VWD90Q Yes
ChEBI CHEBI:10093 Yes
ChEMBL CHEMBL15245 Yes
Chemical data
Formula C21H26N2O3
Mol. mass 354.44 g/mol (base)
390.90 g/mol (hydrochloride)
SMILES[show]
InChI[show]
Yes (what is this?) (verify)
Yohimbine is a mild MAOI with stimulant and aphrodisiac effects. It is sold as prescription medicine in pure form for the treatment of sexual dysfunction. Yohimbine was explored as a remedy for type 2 diabetes in animal and human models carrying polymorphisms of the α2A-adrenergic receptor gene.[2]

Common brand names for yohimbine are: Erex, Testomar, Yocon, Yohimar, Yohimbe.

Contents [hide]
1 Research
2 Medical uses
2.1 Indications
2.1.1 SSRI side-effects
2.1.2 Sexual dysfunction
2.1.2.1 Dosage
2.1.3 Fat loss
2.1.4 Other uses
2.2 Adverse effects
2.3 Precautions and contraindications
2.4 Interactions
2.4.1 MAOIs
2.4.2 Stimulants
3 Sports
4 Pharmacology
4.1 Pharmacologic profile
5 Synthesis
5.1 Laboratory synthesis
5.2 Biosynthesis
6 See also
7 References
Research[edit]
Yohimbine primarily acts as an antagonist of α2 receptors.[3] Additionally, it inhibits the function of monoamine oxidase enzymes, although it is not clear if it is a RIMA, MAOA, or MAOB inhibitor.

RIMAs, like moclobemide (an antidepressant), do not require dietary restrictions. Many people have been supplementing with yohimbine on normal diets (containing tyramine and phenylalanine, found in most cheeses and fish respectively) with no adverse effects. MAOIs are normally contraindicated for use with tyrosine-rich food,[citation needed] but recently, numerous[citation needed] companies have begun combining yohimbine with tyrosine in their energy products.[4] However, tyrosine failed to potentiate the effect of yohimbine except for somewhat augmenting the increase in DHPG.[5]

When yohimbine are used in pharmahuasca it does not have any MAOI effects on tryptamines, e.g. DMT keeps being orally inactive. This suggest that yohimbine is a MAOB inhibitor. A range of cacti contain tyramine, including the Echinopsis pachanoi (syn. Trichocereus pachanoi), known as the San Pedro cactus which also contain the phenylethylamine mescaline.[6] Multiple drug use with yohimbine and mescaline cactus are inconclusive.[citation needed]

Overdoses of yohimbine can cause priapism. Normally priapism is treated with pseudoephedrine, but in combination with MAOIs like yohimbine it can lead to hypertensive reactions.[7] The first step in management may be blood exchange transfusion.[citation needed]

Medical uses[edit]
Indications[edit]
SSRI side-effects[edit]
MAOI and SSRI are normally never mixed as a rule of thumb. However, yohimbine, with its weak MAOI activity, has safely been used to treat sexual side-effects caused by some SSRI antidepressants (see below for more information about sexual dysfunction).[medical citation needed] Also, 14 mg yohimbine increases salivation, so yohimbine could have a potential interest in the treatment of dry mouths,[8] another common side-effect caused by SSRIs. In fact, doctors believe that heartburn, another common SSRI side-effect, is caused by dry mouth because it reduces the amount of saliva running down the esophagus (saliva is known to neutralize excess acid in the stomach).[9]

Sexual dysfunction[edit]
Main article: Sexual dysfunction
The NIH states that yohimbine hydrochloride is the standardized form of yohimbine that is available as a prescription medicine in the United States, and that it has been shown in human studies to be effective in the treatment of male impotence.[10] Yohimbine has been shown to be effective in the treatment of orgasmic dysfunction in men.[11] Yohimbine has also been used to treat hypoactive sexual desire disorder (reduced libido) in women.[12]

Large doses of yohimbe have caused priapism.[13] However, controlled studies suggest that it is not always an effective treatment for impotence, and evidence of increased sex drive (libido) is anecdotal only.[14]

It cannot be excluded that orally administered yohimbine can have a beneficial effect in some patients with ED. The conflicting results available may be attributed to differences in drug design, patient selection, and definitions of positive response. Generally, however, available results of treatment are not impressive.[15]
Yohimbine blocks the pre- and post-synaptic α2 receptors. Blockade of post-synaptic α2 receptors causes minor corpus cavernosum smooth muscle relaxation. In fact, 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, nitric oxide attenuates norepinephrine vasoconstriction. Continuous administration of yohimbine, as opposed to on-demand administration, might result in less norepinephrine output due to increased turnover, or α1 receptors down regulation via a feedback mechanism, not causing the vasoconstriction due to excessive norepinephrine release which can be seen often with on-demand administration. α1 blockers prevent vasoconstriction caused by norepinephrine as well.[16]

Dosage[edit]
Anorgasmia or reduced libido: 5.4-16.2 mg a day 1–2 hours before sexual activity.[17] or 5.4 mg three times a day[18]
Erectile dysfunction: A suggested first line treatment for mild to moderate ED are a combination of 6 mg yohimbine hydrochloride and 6000 mg arginine glutamate (50% arginine, 50% glutamic acid).[19] Other doses of yohimbine alone to treat ED are 15 to 30 mg a day[20] 1–2 hours before sexual activity.[18]
Fat loss[edit]
There is no conclusive evidence for yohimbine to be of benefit in bodybuilding or weight loss.[21]

Other uses[edit]
Yohimbine has also been used for xerostomia, as a blood pressure boosting agent in autonomic failure, and as a probe for noradrenergic activity.[unreliable medical source?]

The addition of yohimbine to fluoxetine or venlafaxine has also been found to potentiate the antidepressant action of both of these agents.[22]

Yohimbine has been used to facilitate recall of traumatic memories in the treatment of post traumatic stress disorder (PTSD).[23] Use of yohimbine outside of therapeutic settings may not be appropriate for persons suffering from PTSD.[24] In pharmacology, yohimbine is used as a probe for α2-adrenoceptor. In veterinary medicine, yohimbine is used to reverse anesthesia from the drug xylazine in small and large animals.

Adverse effects[edit]
Depending on dosage, yohimbine can either increase or decrease systemic blood pressure (through vasoconstriction or vasodilation, respectively); small amounts of yohimbine can increase blood pressure, while large amounts can dangerously lower blood pressure.[7]

The therapeutic index of yohimbine is quite low; the range between an effective dose and a dangerous dose is very narrow.[25] A typical dose for sexual dysfunction would be 15–30 mg, whereas 100 mg would be considered dangerous. This may also lead to the precipitation of panic disorder type reactions, heart attack, and possibly death.

Hallucinations or paralysis may occur with doses greater than 40 mg.[26] Higher doses of oral yohimbine may create numerous side effects, such as rapid heart rate, overstimulation, insomnia and/or sleeplessness. Some effects in rare cases were panic attacks, hallucinations, headaches, dizziness, and skin flushing.[25]

More serious adverse effects may include seizures and renal failure. Yohimbine should not be consumed by anyone with liver, kidney, heart disease, or a psychological disorder.[25]

Precautions and contraindications[edit]
Yohimbe bark is on the FDA list of dangerous supplements.[27] The levels of yohimbine that are present in yohimbe bark extract are variable and often very low.[10] Therefore, although yohimbe bark has been used traditionally to reduce male erectile dysfunction, there is not enough scientific evidence to form a definitive conclusion in this area.

In Africa, yohimbe has traditionally been used as an aphrodisiac.[28] However, it is important to note that while the terms yohimbine, yohimbine hydrochloride, and yohimbe bark extract are related, they are not interchangeable.[10]

Yohimbine is an alkaloid naturally found, along with several other active alkaloids, in Pausinystalia yohimbe (Yohimbe), Rauwolfia serpentina (Indian Snakeroot), and Alchornea floribunda (Niando). Yohimbine has been used as an over-the-counter dietary supplement in herbal extract form.

In addition to the main active chemical, yohimbine, Pausinystalia yohimbe contains approximately 55 other alkaloids, of which yohimbine accounts for 1% to 20% of total alkaloids. Among them, corynanthine is an α1 receptor blocker. Hence the use of yohimbe extract in sufficient dosages may provide concomitant α1 and α2 receptors blockade and thus may better enhance erections than yohimbine alone.[16]

Pausinystalia yohimbe is currently threatened with extinction in its native habitat due to international demand.[citation needed] Its conservation is difficult because the bioactivity of the tree has led many Western governments to declare it a proscribed species.

Interactions[edit]
MAOIs[edit]
At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with yohimbine.[29]

Stimulants[edit]
Research on cats suggests that yohimbine increases the effects of catecholaminergic stimulants, namely amphetamine and modafinil.[30]

Sports[edit]
Sport supplements with yohimbine as the main ingredient are sold as purported energy boosters.[citation needed]

Pharmacology[edit]
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 D2 receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT7, and D3 receptors.[31][32] It behaves as an antagonist at α1-adrenergic, α2-adrenergic, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and D2, and as a partial agonist at 5-HT1A.[31][33][34][35] Yohimbine interacts with serotonin and dopamine receptors in high concentrations.[36]

Pharmacologic profile[edit]
Molecular Target Binding Affinity (Ki in nM)[37] Pharmacologic Action
[31][33][34][35][38] 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
Synthesis[edit]
Laboratory synthesis[edit]
A laboratory synthesis of yohimbine has been developed.

Yohimbine synthesis.png

Biosynthesis[edit]
The biosynthesis (best studied in Catharansus roseus of yohimbine, like that of other indole alkaloids, begins with the condensation of Tryptamine (which contains the A and B rings) and Secologanin by strictosidine synthase into strictosidine, the precursor to many monoterpene indole alkaloids. This first step forms the C ring of the molecule. Strictosidine beta-glucosidase then cleaves the glycosidic bond, yielding the strictosidine aglycon, which can spontaneously isomerize to the "dialdehyde" form[39]. The aldehyde indicated can then condense with the nitrogen in the 6-membered ring, forming an iminium along with the D ring of yohimbine. Following a rearrangement of the vinyl group, the iminium group is hydrogenated, yielding geissoschizine[40]. The biosynthetic progression from geissoschizine to yohimbine has not yet been characterized; however, the ring E-closing process could speculatively involve another alkene isomerization as well as an enol-to-aldehyde tautomerization, allowing for a ring closing step which would simultaneously set the stereochemistry of the E ring, and complete the biosynthesis of the natural product (dashed arrows).



Biosynthetic pathway of yohimbine

[guns01]

Tweetyohimbine is a great fat loss and sex aid supplement. now the draw back is that if you dose it to high for to long it can become toxic and crank your body temp through the roof. great addition for fat burning though

[MOUNTAIN-MAN]

Tweet

yohimbine is a great fat loss and sex aid supplement. now the draw back is that if you dose it to high for to long it can become toxic and crank your body temp through the roof. great addition for fat burning though

yes sr i take it ed prior to work out

[6p6]

TweetBeen a long time since I used yohimbe maybe need to add it in for fun

[Yohimbe]

TweetYep, there are some great benefits from me lol.