Jump to content

Yohimbine: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
its now RX only in the us it was OTC in 2007
No edit summary
Line 52: Line 52:
}}
}}


'''Yohimbine''' is a mild [[monoamine oxidase inhibitor|MAOI]] with [[stimulant]] and [[aphrodisiac]] effects. It is sold as [[prescription drug|prescription]] [[medicine]] in pure form for the [[therapy|treatment]] of [[sexual dysfunction]]. Yohimbine was explored as a remedy for [[type 2 diabetes]] in animal and human models carrying polymorphisms of the α<sub>2A</sub>-adrenergic receptor gene.<ref>{{cite journal |last1=Rosengren |first1=A. H. |last2=Jokubka |first2=R. |last3=Tojjar |first3=D. |last4=Granhall |first4=C. |last5=Hansson |first5=O. |last6=Li |first6=D.-Q. |last7=Nagaraj |first7=V. |last8=Reinbothe |first8=T. M. |last9=Tuncel |first9=J. |title=Overexpression of Alpha2A-Adrenergic Receptors Contributes to Type 2 Diabetes |journal=Science |volume=327 |issue=5962 |pages=217–20 |year=2009 |pmid=19965390 |doi=10.1126/science.1176827}}</ref>
'''Yohimbine''' is a mild [[monoamine oxidase inhibitor|MAOI]] with [[stimulant]] and [[aphrodisiac]] effects. It is sold as [[prescription drug|prescription]] [[medicine]] in pure form for the [[therapy|treatment]] of [[sexual dysfunction]]. Yohimbine was explored as a remedy for [[type 2 diabetes]] in animal and human models carrying polymorphisms of the α<sub>2A</sub>-adrenergic receptor gene.<ref>{{cite journal |last1=Rosengren |first1=A. H. |last2=Jokubka |first2=R. |last3=Tojjar |first3=D. |last4=Granhall |first4=C. |last5=Hansson |first5=O. |last6=Li |first6=D.-Q. |last7=Nagaraj |first7=V. |last8=Reinbothe |first8=T. M. |last9=Tuncel |first9=J. |title=Overexpression of Alpha2A-Adrenergic Receptors Contributes to Type 2 Diabetes |journal=Science |volume=327 |issue=5962 |pages=217–20 |year=2009 |pmid=19965390 |doi=10.1126/science.1176827}}</ref> Donkeys


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

Revision as of 20:19, 25 October 2013

Yohimbine
Clinical data
Trade namesActibine, Erex, Testomar, Yocon, Yohimar, Yohimbe
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Identifiers
  • 17α-hydroxy-yohimban-16α-
    carboxylic acid methyl ester
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.157 Edit this at Wikidata
Chemical and physical data
FormulaC21H26N2O3
Molar mass354.44 g/mol (base)
390.90 g/mol (hydrochloride) g·mol−1
3D model (JSmol)
  • O=C(OC)[C@@H]5[C@H]4C[C@H]3c2nc1ccccc1c2CCN3C[C@@H]4CC[C@@H]5O
  • 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 checkY
  • Key:BLGXFZZNTVWLAY-SCYLSFHTSA-N checkY
  (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.[1] Donkeys

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

Synthesis

Research

Yohimbine primarily acts as an antagonist of α2 receptors.[2] 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 like most cheeses and fish respectively) with no adverse effects. MAOIs are normally contradicted for use with tyrosine rich food[citation needed], but recently numerous[citation needed] companies have taken to combining yohimbine with tyrosine in their fat burners, and energy products.[3] However, tyrosine failed to potentiate the effect of yohimbine except for somewhat augmenting the increase in DHPG.[4]

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.[5] Poly 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.[6] The first step in management may be blood exchange transfusion[citation needed].

Medical uses

Indications

SSRI side-effects

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,[7] another common side-effect caused 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 which is known to neutralize excess acid in the stomach.[8]

Sexual dysfunction

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 has been shown in human studies to be effective in the treatment of male impotence.[9] Yohimbine has been shown to be effective in the treatment of orgasmic dysfunction in men.[10] Yohimbine has also been used to treat hypoactive sexual desire disorder (reduced libido) in women[medical citation needed].

Large doses of yohimbe have caused priapism.[11] However, controlled studies suggest that it is not always an effective treatment for impotence, and evidence of increased sex drive (libido) is anecdotal only.[12]

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.[13]

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. Whether 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, 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.[14]

Dosage
  • Anorgasmia or reduced libido: 5.4-16.2 mg a day 1–2 hours before sexual activity.[15] or 5.4 mg three times a day[16]
  • 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).[17] Other doses of yohimbine alone to treat ED are 15 to 30 mg a day[18] 1–2 hours before sexual activity.[16]

Fat loss [unreliable medical source?]

According to one study, oral yohimbine supplementation may actuate significant fat loss in athletes, though this study is self-reported and did not monitor caloric intake.[19] Numerous bodybuilding supplement companies sell formulations of yohimbine for transdermal delivery to effect a local reduction of adipose tissue, although the experimental evidence for its efficacy is limited.[20][unreliable source?]

Other uses

Yohimbine has also been used as a blood pressure boosting agent in autonomic failure, xerostomia, 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.[21]

Yohimbine has been used to facilitate recall of traumatic memories in the treatment of post traumatic stress disorder (PTSD).[22] Use of yohimbine outside therapeutic settings may not be appropriate for persons suffering from PTSD.[23] 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

Depending on dosage yohimbine can both lower and increase systemic blood pressure, known as vasodilation and vasoconstriction respectively; small amounts of yohimbine can increase blood pressure while large amounts can dangerously lower blood pressure.[6]

The therapeutic index of yohimbine is quite low; the range between an effective dose and a dangerous dose is very narrow.[24] 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.[25] 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.[24]

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.[24]

Precautions and contraindications

Yohimbe bark is on the FDA list of dangerous supplements.[26] The levels of yohimbine that are present in yohimbe bark extract are variable and often very low.[9] 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.[27] However, it is very important to note that while the terms yohimbine, yohimbine hydrochloride, and yohimbe bark extract are related, they are not interchangeable.[9]

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

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.[14]

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

MAOIs

At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with yohimbine.[28]

NRIs

Yohimbine in combination with norepinephrine reuptake inhibitor, such as dextromethorphan, tramadol, some antidepressants and central nervous system stimulants used to treat ADHD, can cause a hypertensive crises. This is due to those drugs in combination with an a2 receptor antagonist leads to too much norepinephrine in the brain, which causes blood pressure to spike to dangerous levels.

Yohimbine in combination with modafinil is frequently associated with nausea, dangerous acute rapid heart beat, and acute increased blood pressure. Yohimbine exhibits some degree of MAOI activity while modafinil has been shown to increase levels of various monamines and therefore could result in severe risk of dangerous side effects.

Stimulants

Research on cats suggests that yohimbine increases the effects of catecholaminergic stimulants, namely amphetamine and modafinil.[29]

Sports

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

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 D2 receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT7, and D3 receptors.[30][31] 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.[30][32][33][34] Its intrinsic activities at the other sites listed are unclear/unknown, but it is probably mostly antagonistic at them.[citation needed] Yohimbine interact with serotonin and dopamine receptors in high concentrations.[35]

Pharmacologic Profile of Yohimbine

Molecular Target Binding Affinity (Ki in nM)[36] Pharmacologic Action[30][32][33][34] Species Source
SERT 1,000 Inhibitor Human Frontal Cortex
DAT 1,000 Inhibitor Rat Brain
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-HT2C >10,000 Unknown Human Cloned
5-HT3 >10,000 Unknown Rat and Mouse Cloned, Cortex & NG108-15
5-HT5A 1,000 Unknown Rat and Mouse 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
D1 >10,000 Unknown Human Cloned
D2 339 Unknown Human Cloned
D3 3,235 Unknown Human Cloned

See also

References

  1. ^ Rosengren, A. H.; Jokubka, R.; Tojjar, D.; Granhall, C.; Hansson, O.; Li, D.-Q.; Nagaraj, V.; Reinbothe, T. M.; Tuncel, J. (2009). "Overexpression of Alpha2A-Adrenergic Receptors Contributes to Type 2 Diabetes". Science. 327 (5962): 217–20. doi:10.1126/science.1176827. PMID 19965390.
  2. ^ Verwaerde, P (1997). "Effects of yohimbine, an α2 receptors antagonist, on experimental neurogenic orthostatic hypotension". Fundamental & clinical pharmacology. 11 (6): 567–75. PMID 9444525. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ "Yohimbe Supplements". Livestrong.Com. Retrieved 2013-05-26.
  4. ^ USA (2013-03-25). "Differential effects of yoh... [Res Commun Chem Pathol Pharmacol. 1988] - PubMed - NCBI". Ncbi.nlm.nih.gov. Retrieved 2013-05-26.
  5. ^ "Visionary Cactus Guide". Lycaeum.
  6. ^ a b "Yohimbe: MedlinePlus Supplements". Nlm.nih.gov. Retrieved 2013-05-26.
  7. ^ USA (2013-03-25). "Yohimbine increases human salivary secretion". Ncbi.nlm.nih.gov. Retrieved 2013-05-26.
  8. ^ http://www.acidrefluxsymptomsnow.com/Does-zoloft-causes-heartburn.html
  9. ^ a b c "Yohimbe: MedlinePlus Supplements". nlm.nih.gov. November 19, 2010. Retrieved December 13, 2010.
  10. ^ Adeniyi AA, Brindley GS, Pryor JP, Ralph DJ (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ USA (2013-03-25). "Refractory priapism associated with ingestion ... [J Med Toxicol. 2009] - PubMed - NCBI". Ncbi.nlm.nih.gov. Retrieved 2013-05-26.
  12. ^ Andersson KE (2001). "Pharmacology of penile erection". Pharmacological Reviews. 53 (3): 417–50. PMID 11546836. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Andersson, Karl-Erik; Steers, William D. (1998). "The pharmacological basis of sexual therapeutics". In Morales, Alvaro (ed.). Erectile dysfunction: issues in current pharmacotherapy. London: Martin Dunitz. pp. 97–124 [114]. ISBN 978-1-85317-577-0. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  14. ^ a b 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.
  15. ^ "Pharmacotherapy- Treatment of OCD - OCD Research - Stanford University School of Medicine". Ocd.stanford.edu. 2008-06-20. Retrieved 2013-05-26.
  16. ^ a b Neuropsychiatry - Google Books. Books.google.se. Retrieved 2013-05-26.
  17. ^ 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.
  18. ^ "Dietary Supplement Information Bureau –". Naturalproductsinfo.org. Retrieved 2013-05-26.
  19. ^ Ostojic SM (2006). "Yohimbine: the effects on body composition and exercise performance in soccer players". Research in Sports Medicine. 14 (4): 289–99. doi:10.1080/15438620600987106. PMID 17214405.
  20. ^ "Fat Loss, alpha2-Adrenoceptors and Yohimbine, Part 2". Mesomorphosis.com. 1998-12-01. Retrieved 2013-05-26.
  21. ^ 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.
  22. ^ van der Kolk, Bessel A. (1995). "The Treatment of Post Traumatic Stress Disorder". In Hobfoll, Stevan E.; De Vries, Marten W. (eds.). Extreme stress and communities: impact and intervention. Boston: Kluwer Academic Publishers. pp. 421–44. ISBN 978-0-7923-3468-2. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  23. ^ Morgan CA; Grillon C; Southwick SM; et al. (1995). "Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder". Psychopharmacology. 117 (4): 466–71. doi:10.1007/BF02246220. PMID 7604149. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  24. ^ a b c Prescription for Nutritional Healing, fourth edition Phyllis A. Balch, CNC
  25. ^ "Yohimbine Dangers". Livestrong.Com. Retrieved 2013-05-26.
  26. ^ "Yohimbe Bark Supplements for ED: Side Effects, Safety, Dangers, and More". Webmd.com. 2012-08-06. Retrieved 2013-05-26.
  27. ^ Yohimbe. National Center for Complementary and Alternative Medicine.
  28. ^ HealthCare.com. "Interactions with Yohimbine". Healthcare.com. Retrieved 2013-05-26.
  29. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 1359924, please use {{cite journal}} with |pmid=1359924 instead.
  30. ^ a b c Millan MJ; Newman-Tancredi A; Audinot V; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  31. ^ "PDSP Ki Database".
  32. ^ a b Arthur JM, Casañas SJ, Raymond JR (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ a b Kaumann AJ (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  34. ^ a b Baxter GS, Murphy OE, Blackburn TP (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ "Yohimbine (PIM 567)". Inchem.org. Retrieved 2013-05-26.
  36. ^ National Institute of Mental Health. "PDSP Ki Database". University of North Carolina. Retrieved 5 July 2013.
Retrieved from "https://wiki.riteme.site/w/index.php?title=Yohimbine&oldid=578737112"