You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:33:00 UTC
HMDB IDHMDB15464
Secondary Accession NumbersNone
Metabolite Identification
Common NameYohimbine
DescriptionYohimbine is only found in individuals that have used or taken this drug. It is a plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [PubChem]Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. The exact mechanism for its use in impotence has not been fully elucidated. However, yohimbine may exert its beneficial effect on erectile ability through blockade of central alpha 2-adrenergic receptors producing an increase in sympathetic drive secondary to an increase in norepinephrine release and in firing rate of cells in the brain noradrenergic nuclei. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors.
Structure
Thumb
Synonyms
ValueSource
(+)-YohimbineChEBI
(16alpha,17alpha)-17-Hydroxyyohimban-16-carboxylic acid methyl esterChEBI
17alpha-Hydroxyyohimban-16alpha-carboxylic acid methyl esterChEBI
AphrodineChEBI
CorynineChEBI
JohimbinChEBI
QuebrachinChEBI
QuebrachineChEBI
Yohimbic acid methyl esterChEBI
YohimbinChEBI
Chemical FormulaC21H26N2O3
Average Molecular Weight354.4427
Monoisotopic Molecular Weight354.194342708
IUPAC Namemethyl (1S,15R,18S,19R,20S)-18-hydroxy-3,13-diazapentacyclo[11.8.0.0²,¹⁰.0⁴,⁹.0¹⁵,²⁰]henicosa-2(10),4,6,8-tetraene-19-carboxylate
Traditional Nameyohimbine
CAS Registry Number146-48-5
SMILES
[H][C@@]12CC[C@H](O)[C@H](C(=O)OC)[C@@]1([H])C[C@]1([H])N(CCC3=C1NC1=CC=CC=C31)C2
InChI Identifier
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
InChI KeyInChIKey=BLGXFZZNTVWLAY-SCYLSFHTSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as yohimbine alkaloids. These are alkaloids containing the pentacyclic yohimban skeleton. The Yohimbinoid alkaloids contain a carbocyclic ring E arising through C-17 to C-18 bond formation in a corynantheine precursor.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassYohimbine alkaloids
Sub ClassNot Available
Direct ParentYohimbine alkaloids
Alternative Parents
Substituents
  • Yohimbine
  • Corynanthean skeleton
  • Yohimbine alkaloid
  • Pyridoindole
  • Beta-carboline
  • Indole or derivatives
  • Indole
  • Aralkylamine
  • Beta-hydroxy acid
  • Benzenoid
  • Piperidine
  • Hydroxy acid
  • Heteroaromatic compound
  • Methyl ester
  • Pyrrole
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Adrenergic alpha-Antagonists
  • Mydriatics
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point241 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.48e-01 g/LNot Available
LogP2.73HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.35 mg/mLALOGPS
logP2.36ALOGPS
logP2.1ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)14.68ChemAxon
pKa (Strongest Basic)7.65ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area65.56 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity99.63 m3·mol-1ChemAxon
Polarizability40.22 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01392
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01392
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01392
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID8622
KEGG Compound IDC09256
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkYohimbine
NuGOwiki LinkHMDB15464
Metagene LinkHMDB15464
METLIN IDNot Available
PubChem Compound8969
PDB IDNot Available
ChEBI ID10093
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
References
  1. Laurila JM, Xhaard H, Ruuskanen JO, Rantanen MJ, Karlsson HK, Johnson MS, Scheinin M: The second extracellular loop of alpha2A-adrenoceptors contributes to the binding of yohimbine analogues. Br J Pharmacol. 2007 Aug;151(8):1293-304. Epub 2007 Jun 11. [17558432 ]
  2. Zadori ZS, Shujaa N, Fulop K, Dunkel P, Gyires K: Pre- and postsynaptic mechanisms in the clonidine- and oxymetazoline-induced inhibition of gastric motility in the rat. Neurochem Int. 2007 Oct;51(5):297-305. Epub 2007 Jun 30. [17664022 ]
  3. Paul BZ, Jin J, Kunapuli SP: Molecular mechanism of thromboxane A(2)-induced platelet aggregation. Essential role for p2t(ac) and alpha(2a) receptors. J Biol Chem. 1999 Oct 8;274(41):29108-14. [10506165 ]
  4. Kalkman HO, Loetscher E: alpha2C-Adrenoceptor blockade by clozapine and other antipsychotic drugs. Eur J Pharmacol. 2003 Feb 21;462(1-3):33-40. [12591093 ]
  5. Ozdogan UK, Lahdesmaki J, Scheinin M: The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene. Eur J Pharmacol. 2006 Jan 4;529(1-3):105-13. Epub 2005 Dec 2. [16325800 ]
  6. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular weight:
49953.1
References
  1. Freitag A, Wessler I, Racke K: Adrenoceptor- and cholinoceptor-mediated mechanisms in the regulation of 5-hydroxytryptamine release from isolated tracheae of newborn rabbits. Br J Pharmacol. 1996 Sep;119(1):91-8. [8872361 ]
  2. Cleary L, Vandeputte C, Docherty JR: Investigation of neurotransmission in vas deferens from alpha(2A/D)-adrenoceptor knockout mice. Br J Pharmacol. 2002 Jul;136(6):857-64. [12110610 ]
  3. Gyires K, Mullner K, Ronai AZ: Functional evidence that gastroprotection can be induced by activation of central alpha(2B)-adrenoceptor subtypes in the rat. Eur J Pharmacol. 2000 May 19;396(2-3):131-5. [10822066 ]
  4. Takada K, Clark DJ, Davies MF, Tonner PH, Krause TK, Bertaccini E, Maze M: Meperidine exerts agonist activity at the alpha(2B)-adrenoceptor subtype. Anesthesiology. 2002 Jun;96(6):1420-6. [12170055 ]
  5. Alonso E, Garrido E, Diez-Fernandez C, Perez-Garcia C, Herradon G, Ezquerra L, Deuel TF, Alguacil LF: Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and alpha2-adrenoceptor gene expression in hippocampus. Neurosci Lett. 2007 Jan 29;412(2):163-7. Epub 2006 Nov 22. [17123717 ]
  6. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
References
  1. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular weight:
43567.5
References
  1. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
  2. Kaumann AJ: Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):149-54. [6136920 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular weight:
46106.3
References
  1. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
  2. Kaumann AJ: Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):149-54. [6136920 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
References
  1. Baxter GS, Murphy OE, Blackburn TP: Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle. Br J Pharmacol. 1994 May;112(1):323-31. [8032658 ]
  2. Kaumann AJ: Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):149-54. [6136920 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
References
  1. Baxter GS, Murphy OE, Blackburn TP: Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle. Br J Pharmacol. 1994 May;112(1):323-31. [8032658 ]
  2. Kaumann AJ: Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):149-54. [6136920 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular weight:
41906.4
References
  1. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular weight:
49521.6
References
  1. Lalchandani SG, Lei L, Zheng W, Suni MM, Moore BM, Liggett SB, Miller DD, Feller DR: Yohimbine dimers exhibiting selectivity for the human alpha 2C-adrenoceptor subtype. J Pharmacol Exp Ther. 2002 Dec;303(3):979-84. [12438517 ]
  2. Rizzo CA, Ruck LM, Corboz MR, Umland SP, Wan Y, Shah H, Jakway J, Cheng L, McCormick K, Egan RW, Hey JA: Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein. Eur J Pharmacol. 2001 Feb 16;413(2-3):263-9. [11226402 ]
  3. Cleary L, Murad K, Bexis S, Docherty JR: The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist. Auton Autacoid Pharmacol. 2005 Oct;25(4):135-41. [16176444 ]
  4. Kalkman HO, Loetscher E: alpha2C-Adrenoceptor blockade by clozapine and other antipsychotic drugs. Eur J Pharmacol. 2003 Feb 21;462(1-3):33-40. [12591093 ]
  5. Cleary L, Vandeputte C, Docherty JR: Investigation of neurotransmission in vas deferens from alpha(2A/D)-adrenoceptor knockout mice. Br J Pharmacol. 2002 Jul;136(6):857-64. [12110610 ]
  6. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular weight:
44224.3
References
  1. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: 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. 2000 Feb;35(2):79-95. [10611634 ]