|Systematic (IUPAC) name|
carboxylic acid methyl ester
|Trade names||Actibine, Erex, Testomar, Yocon, Yohimar, Yohimbe|
|Legal status||Prescription Only (S4) (AU) OTC supplement (US)|
|Excretion||Urine (as metabolites)|
|ATC code||G04 QV03|
|Mol. mass||354.44 g/mol (base)
390.90 g/mol (hydrochloride)
|(what is this?)|
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.
Common brand names for yohimbine are: Erex, Testomar, Yocon, Yohimar, Yohimbe.
- 1 Research
- 2 Medical uses
- 3 Sports
- 4 Pharmacology
- 5 Synthesis
- 6 See also
- 7 References
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 tyramine-rich food, but recently, numerous companies have begun combining yohimbine with tyramine in their energy products. However, tyramine failed to potentiate the effect of yohimbine except for somewhat augmenting the increase in DHPG.
When yohimbine is used in pharmahuasca it does not have any MAOI effects on tryptamines, e.g. DMT remains 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. Multiple drug use with yohimbine and mescaline cactus are inconclusive.
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. The first step in management may be blood exchange transfusion.
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, 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).[medical citation needed]
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. Yohimbine has been shown to be effective in the treatment of orgasmic dysfunction in men. Yohimbine has also been used to treat hypoactive sexual desire disorder (reduced libido) in women.
Large doses of yohimbe have caused priapism. However, controlled studies suggest that it is not always an effective treatment for impotence, and evidence of increased sex drive (libido) is anecdotal only.
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.
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 increased norepinephrine reuptake and thereby reduced vasoconstriction from reduced α1 adrenergic receptors stimulation by it's feedback down regulation mechanism -unlike on-demand administration that produces excessive norepinephrine release and bottlenecked reuptake. And α1 blockers on-demand reduce vasoconstriction caused by excessive norepinephrine release.
- Anorgasmia or reduced libido: 5.4-16.2 mg a day 1–2 hours before sexual activity. or 5.4 mg three times a day
- 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). Other doses of yohimbine alone to treat ED are 15 to 30 mg a day 1–2 hours before sexual activity.
Yohimbine has shown to increase lipolysis in multiple studies.
Administered prior to exercise, it boosts lipolysis and serum FFA levels both during and following exercise; blockade of adipocyte alpha-2 adrenoreceptors makes at least a modest contribution to this pro-lipolytic activity. Pre-exercise yohimbine administration has the potential to down-regulate the lipoprotein lipase activity of visceral adipocytes, increase lipolysis in refractory gynoid fat depots, and improve the impaired lipolytic response to exercise in the elderly.
Combining yohimbine with stimulants such as caffeine and/or ephedrine could possibly further increase lipolysis due to the potential for yohimbine to increase catecholaminergic stimulant activity.
Yohimbine has been used to facilitate recall of traumatic memories in the treatment of post traumatic stress disorder (PTSD). Use of yohimbine outside of therapeutic settings may not be appropriate for persons suffering from PTSD. 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.
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.
The therapeutic index of yohimbine is quite low; the range between an effective dose and a dangerous dose is very narrow. 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. 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.
Precautions and contraindications
Yohimbe bark is on the FDA list of dangerous supplements. The levels of yohimbine that are present in yohimbe bark extract are variable and often very low. 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. However, it is important to note that while the terms yohimbine, yohimbine hydrochloride, and yohimbe bark extract are related, they are not interchangeable.
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.
Pausinystalia yohimbe is currently threatened with extinction in its native habitat due to international demand. Its conservation is difficult because the bioactivity of the tree has led many Western governments to declare it a proscribed species.
At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with yohimbine.
Sport supplements with yohimbine as the main ingredient are sold as purported energy boosters.
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. 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. Yohimbine interacts with serotonin and dopamine receptors in high concentrations.
|Molecular Target||Binding Affinity (Ki in nM)||Pharmacologic Action
A laboratory synthesis of yohimbine has been developed.
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. 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. 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).
- Hedner, T; Edgar, B; Edvinsson, L; Hedner, J; Persson, B; Pettersson, A (1992). "Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers". European Journal of Clinical Pharmacology 43 (6): 651–656. doi:10.1007/BF02284967. PMID 1493849.
- Rosengren, A. H.; Jokubka, R.; Tojjar, D.; Granhall, C.; Hansson, O.; Li, D.-Q.; Nagaraj, V.; Reinbothe, T. M. et al. (2009). "Overexpression of Alpha2A-Adrenergic Receptors Contributes to Type 2 Diabetes". Science 327 (5962): 217–20. doi:10.1126/science.1176827. PMID 19965390.
- Verwaerde, P; Tran, MA; Montastruc, JL; Senard, JM; Portolan, G (1997). "Effects of yohimbine, an α2 receptors antagonist, on experimental neurogenic orthostatic hypotension.". Fundamental & clinical pharmacology 11 (6): 567–75. doi:10.1111/j.1472-8206.1997.tb00862.x. PMID 9444525.
- "Yohimbe Supplements". Livestrong.Com. Retrieved 2013-05-26.
- USA (2013-03-25). "Differential effects of yoh... [Res Commun Chem Pathol Pharmacol. 1988] - PubMed - NCBI". Ncbi.nlm.nih.gov. Retrieved 2013-05-26.
- Edwards, D. J.; Sorisio, D. A. (1988). "Differential effects of yohimbine and phenoxybenzamine on norepinephrine metabolites in rat brain". Research communications in chemical pathology and pharmacology 62 (2): 195–206. PMID 3251333.
- "Yohimbe: MedlinePlus Supplements". Nlm.nih.gov. Retrieved 2013-05-26.
- USA (2013-03-25). "Yohimbine increases human salivary secretion". Ncbi.nlm.nih.gov. Retrieved 2013-05-26.
- "Yohimbe: MedlinePlus Supplements". nlm.nih.gov. November 19, 2010. Retrieved December 13, 2010.
- Adeniyi AA, Brindley GS, Pryor JP, Ralph DJ (May 2007). "Yohimbine in the treatment of orgasmic dysfunction". Asian Journal of Andrology 9 (3): 403–7. doi:10.1111/J.1745-7262.2007.00276.x. PMID 17486282.
- Myers, A.; Barrueto, F. (2009). "Refractory priapism associated with ingestion of yohimbe extract". Journal of medical toxicology : official journal of the American College of Medical Toxicology 5 (4): 223–225. doi:10.1007/BF03178272. PMC 3550410. PMID 19876857.
- Andersson KE (September 2001). "Pharmacology of penile erection". Pharmacological Reviews 53 (3): 417–50. PMID 11546836.
- Andersson, Karl-Erik; Steers, William D. (1998). "The pharmacological basis of sexual therapeutics". In Morales, Alvaro. Erectile dysfunction: issues in current pharmacotherapy. London: Martin Dunitz. pp. 97–124 . ISBN 978-1-85317-577-0.
- Saenz De Tejada, I; Kim, NN; Goldstein, I; Traish, AM (2000). "Regulation of pre-synaptic alpha adrenergic activity in the corpus cavernosum". International Journal of Impotence Research. 12 Suppl 1: S20–25. doi:10.1038/sj.ijir.3900500. PMID 10845761.
- "Pharmacotherapy- Treatment of OCD - OCD Research - Stanford University School of Medicine". Ocd.stanford.edu. 2008-06-20. Retrieved 2013-05-26.
- Neuropsychiatry - Google Books. Books.google.se. Retrieved 2013-05-26.
- Lebret, T.; Hervéa, J. M.; Gornyb, P.; Worcelc, M.; Botto, H. (2002). "Efficacy and Safety of a Novel Combination of L-Arginine Glutamate and Yohimbine Hydrochloride: A New Oral Therapy for Erectile Dysfunction". European Urology 41 (6): 608–613. doi:10.1016/S0302-2838(02)00175-6. PMID 12074777.
- "Dietary Supplement Information Bureau –". Naturalproductsinfo.org. Retrieved 2013-05-26.
- McCarty, M (June 2002). "Pre-exercise administration of yohimbine may enhance the efficacy of exercise training as a fat loss strategy by boosting lipolysis.". Medical Hypotheses 58 (6): 491–495. doi:10.1054/mehy.2001.1459.
- Dhir, A; Kulkarni, SK (2007). "Effect of addition of yohimbine (α2 receptors antagonist) to the antidepressant activity of fluoxetine or venlafaxine in the mouse forced swim test". Pharmacology 80 (4): 239–43. doi:10.1159/000104877. PMID 17622775.
- van der Kolk, Bessel A. (1995). "The Treatment of Post Traumatic Stress Disorder". In Hobfoll, Stevan E.; De Vries, Marten W. Extreme stress and communities: impact and intervention. Boston: Kluwer Academic Publishers. pp. 421–44. ISBN 978-0-7923-3468-2.
- Morgan CA, Grillon C, Southwick SM et al. (February 1995). "Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder". Psychopharmacology 117 (4): 466–71. doi:10.1007/BF02246220. PMID 7604149.
- Prescription for Nutritional Healing, fourth edition Phyllis A. Balch, CNC.
- "Yohimbine Dangers". Livestrong.Com. Retrieved 2013-05-26.
- "Yohimbe Bark Supplements for ED: Side Effects, Safety, Dangers, and More". Webmd.com. 2012-08-06. Retrieved 2013-05-26.
- Yohimbe. National Center for Complementary and Alternative Medicine.
- HealthCare.com. "Interactions with Yohimbine". Healthcare.com. Retrieved 2013-05-26.
- Lin, J. S.; Roussel, B.; Akaoka, H.; Fort, P.; Debilly, G.; Jouvet, M. (1992). "Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat". Brain Research 591 (2): 319–326. doi:10.1016/0006-8993(92)91713-O. PMID 1359924.
- Millan MJ, Newman-Tancredi A, Audinot V et al. (February 2000). "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". Synapse 35 (2): 79–95. doi:10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X. PMID 10611634.
- "PDSP Ki Database".
- Arthur JM, Casañas SJ, Raymond JR (June 1993). "Partial agonist properties of rauwolscine and yohimbine for the inhibition of adenylyl cyclase by recombinant human 5-HT1A receptors". Biochemical Pharmacology 45 (11): 2337–41. doi:10.1016/0006-2952(93)90208-E. PMID 8517875.
- Kaumann AJ (June 1983). "Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors". Naunyn-Schmiedeberg's Archives of Pharmacology 323 (2): 149–54. doi:10.1007/BF00634263. PMID 6136920.
- Baxter GS, Murphy OE, Blackburn TP (May 1994). "Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle". British Journal of Pharmacology 112 (1): 323–31. doi:10.1111/j.1476-5381.1994.tb13072.x. PMC 1910288. PMID 8032658.
- "Yohimbine (PIM 567)". Inchem.org. Retrieved 2013-05-26.
- National Institute of Mental Health. "PDSP Ki Database". University of North Carolina. Retrieved 5 July 2013.
- "Yohimbine". DrugBank. University of Alberta. Retrieved 12 April 2014.