Yohimbine

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Yohimbine
Yohimbine structure.svg
Yohimbine-3D-balls-Trans.png
Systematic (IUPAC) name
17α-hydroxy-yohimban-16α-
carboxylic acid methyl ester
Clinical data
Legal status
  • AU: S4 (Prescription only)
  • US: OTC supplement
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability 7-86% (mean 33%)
Biological half-life 0.25-2.5 hours[1]
Excretion Urine (as metabolites)
Identifiers
CAS Number 146-48-5 YesY
ATC code G04BE04 (WHO) QV03AB93 (WHO)
PubChem CID: 8969
IUPHAR/BPS 102
DrugBank DB01392 YesY
ChemSpider 8622 YesY
UNII 2Y49VWD90Q YesY
ChEBI CHEBI:10093 YesY
ChEMBL CHEMBL15245 YesY
Chemical data
Formula C21H26N2O3
Molecular mass 354.44 g/mol (base)
390.90 g/mol (hydrochloride)
  • 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 YesY
  • Key:BLGXFZZNTVWLAY-SCYLSFHTSA-N YesY
  (verify)

Yohimbine (/joʊˈhɪmbiːn/)[2] is an indole alkaloid derived from the bark of the Pausinystalia yohimbe tree in Central Africa. It is a veterinary drug used to reverse sedation in dogs and deer. Yohimbine has been studied as a potential treatment for erectile dysfunction but there is insufficient evidence to rate its effectiveness.[3][4] Extracts from yohimbe have been marketed as dietary supplements for improving sexual function.[5]

Uses

Yohimbine is a drug used in veterinary medicine to reverse the effects of xylazine in dogs and deer.[6]

Yohimbe extracts, which contain yohimbine, have been used in traditional medicine and marketed as dietary supplements.[5]

Toxicity

Depending on dosage, yohimbine can either increase or decrease systemic blood pressure (through vasoconstriction or vasodilation, respectively). Because yohimbine has highest affinity for the α2 receptor, small doses can increase blood pressure by causing a relatively selective α2 blockade. Yohimbine also, however, interacts with α1 receptors, albeit with lower affinity; therefore, at higher doses an α1 blockade can occur and supersede the effects of the α2 blockade, leading to a potentially dangerously drop in blood pressure.[3] Higher doses of oral yohimbine may create numerous side effects, such as rapid heart rate, overstimulation, anomalous blood pressure, cold sweating, and insomnia.

Extracts and chemistry

Yohimbe (Pausinystalia johimbe) is a tree that grows in western and central Africa;[7] yohimbine was originally extracted from the bark of yohimbe in 1896 by Adolph Spiegel.[8] In 1943 the correct constitution of yohimbine was proposed by Witkop.[9] Fifteen years later, Van Tamelen used a 23-step synthesis to become the first person to achieve the synthesis of yohimbine.[10][11][12]

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.[13][14] 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.[13][15][16][17] Yohimbine interacts with serotonin and dopamine receptors in high concentrations.[18]

Pharmacologic profile
Molecular Target Binding Affinity
(Ki in nanomolars)[19]		 Pharmacologic Action
[13][15][16][17][20]		 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

Research

Sexual dysfunction

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Main article: Sexual dysfunction

Yohimbine has been studied as a potential treatment for erectile dysfunction but there is insufficient evidence to rate its effectiveness.[3][4] 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.[21]

Yohimbine blocks the pre- and post-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.[22]

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ yohimbine. (n.d.) Collins English Dictionary – Complete and Unabridged. (1991, 1994, 1998, 2000, 2003). Retrieved January 27, 2015 from http://www.thefreedictionary.com/yohimbine
  3. ↑ 3.0 3.1 3.2 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 21 CFR Sec. 522.2670 Yohimbine
  7. ↑ Kew World Checklist of Selected Plant Families, Pausinystalia johimbe
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ 13.0 13.1 13.2 Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ 16.0 16.1 Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ 17.0 17.1 Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ FDA regulations on OTC products
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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