|Systematic (IUPAC) name|
carboxylic acid methyl ester
|Trade names||Actibine, Erex, Testomar, Yocon, Yohimar, Yohimbe|
|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 an indole alkaloid derived from the bark of the Pausinystalia yohimbe tree in Central Africa. It is primarily used as a treatment for erectile dysfunction. Brand names include: Erex, Testomar, Yocon, Yohimar, Yohimbe. It is a stimulant with aphrodisiac and mild MAOI effects that primarily acts as an antagonist of α2 receptors. It is available as a prescription medication in the standardized form, yohimbine hydrochloride, for the treatment of xerostomia and selective serotonin reuptake inhibitor induced sexual dysfunction. Yohimbine produces a profile similar to ADHD.
There is potential for yohimbine to be used as treatment for SSRI induced sexual dysfunction. One study has shown yohimbine's ability to increase physical functioning as well as desire in patients taking an SSRI. Yohimbine has proved to be effective in treating dry mouth caused by anti-depressant use, however much of the evidence has been centered around those taking a tricyclic antidepressant.
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 erectile dysfunction. 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 (under active libido) in women.
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 its 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.
There is no good evidence Yohimbine is useful as an aid to weight loss.
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. Perceptible effects begin under half a miligram. A typical dose for sexual dysfunction would be 15–30 mg, whereas 100 mg would be considered dangerous. Overdose may also precipitate panic-type reactions, heart attack, and possibly death. Some have experienced severe adverse effects under 5 mg.
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, anomalous blood pressure, cold sweating, and insomnia. In rare cases panic attacks, hallucinations, headaches, dizziness, and skin flushing have occurred.
Overdoses of yohimbine can cause priapism. There is little evidence for the use of pseudoephedrine in the treatment of priapism. The America Urology Association recommends phenylephrine intracavernous injection.  In one case report, yohimbine induced priapism was treated with the insertion of a Quackles shunt.
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 alleviate 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.
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.
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
MAOIs are normally contraindicated for use with tyramine-rich food (see the cheese effect). Some companies have combined yohimbine with tyramine in their energy products. However, tyramine failed to potentiate the effect of yohimbine except for somewhat augmenting the increase in DHPG.
Despite its MAOI properties, it does not spare the degradation of tryptamines, (e.g. DMT) which remain orally inactive upon coadministration, suggesting that yohimbine is potentially a selective inhibitor of MAOB.
- 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.
- 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.
- Jacobsen, FM (April 1992). "Fluoxetine-induced sexual dysfunction and an open trial of yohimbine.". The Journal of clinical psychiatry 53 (4): 119–22. PMID 1564046.
- Rispail, Y; Schmitt, L; Berlan, M; Montastruc, JL; Montastruc, P (1990). "Yohimbine increases salivary secretion in depressed patients treated with tricyclic antidepressants.". European journal of clinical pharmacology 39 (4): 425–6. PMID 2076732.
- Bagheri, H; Schmitt, L; Berlan, M; Montastruc, JL (December 1992). "Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants.". British journal of clinical pharmacology 34 (6): 555–8. PMID 1362888.
- "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.
- Cimolai N, Cimolai T (December 2011). "Yohimbine use for physical enhancement and its potential toxicity". J Diet Suppl (Review) 8 (4): 346–54. doi:10.3109/19390211.2011.615806. PMID 22432773.
- 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.
- "Yohimbe: MedlinePlus Supplements". Nlm.nih.gov. Retrieved 2013-05-26.
- Prescription for Nutritional Healing, fourth edition Phyllis A. Balch, CNC.
- "Yohimbine Dangers". Livestrong.Com. Retrieved 2013-05-26.
- Drogo et. al. "GUIDELINE ON THE MANAGEMENT OF PRIAPISM". American Urological Association. Retrieved 3 November 2014.
- Myers, A; Barrueto F, Jr (December 2009). "Refractory priapism associated with ingestion of yohimbe extract.". Journal of medical toxicology : official journal of the American College of Medical Toxicology 5 (4): 223–5. PMID 19876857.
- "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.
- "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.
- 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.