yohimbin

Yohimbine
Clinical data
Routes of; administration	Oral
ATC code	G04BE04 (WHO) QV03AB93 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); US: Dietary supplement;
Pharmacokinetic data
Bioavailability	7-86% (mean 33%)
Biological half-life	0.25-2.5 hours
Excretion	Urine (as metabolites)
Identifiers
	IUPAC name 17α-hydroxy-yohimban-16α-; carboxylic acid methyl ester;
CAS Number	146-48-5 ;
PubChem CID	8969;
IUPHAR/BPS	102;
DrugBank	DB01392 ;
ChemSpider	8622 ;
UNII	2Y49VWD90Q;
ChEBI	CHEBI:10093 ;
ChEMBL	CHEMBL15245 ;
ECHA InfoCard	100.005.157
Chemical and physical data
Formula	C21H26N2O3
Molar mass	354.44 g/mol (base); 390.90 g/mol (hydrochloride)
3D model (JSmol)	Interactive image;
	SMILES O=C(OC)[C@@H]5[C@H]4C[C@H]3c2nc1ccccc1c2CCN3C[C@@H]4CC[C@@H]5O ;
	InChI 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 ; Key:BLGXFZZNTVWLAY-SCYLSFHTSA-N ;
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関: yohimbine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/09/17 04:33:57」(JST)

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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] Extracts from yohimbe have been marketed as dietary supplements for improving sexual function.^[4]

Uses

Yohimbine is a drug used in veterinary medicine to reverse the effects of xylazine in dogs and deer.^[5]

Yohimbe extracts, which contain yohimbine, have been used in traditional medicine and marketed as dietary supplements.^[4]

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 overwhelm the effects of the α₂ blockade, leading to a potentially dangerous drop in blood pressure.^[6] 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-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1F, 5-HT_2B, and D₂ receptors, and weak affinity for the 5-HT_1E, 5-HT_2A, 5-HT_5A, 5-HT₇, and D₃ receptors.^[13]^[14] It behaves as an antagonist at α₁-adrenergic, α₂-adrenergic, 5-HT_1B, 5-HT_1D, 5-HT_2A, 5-HT_2B, and D₂, and as a partial agonist at 5-HT_1A.^[13]^[15]^[16]^[17] Yohimbine interacts with serotonin and dopamine receptors in high concentrations.^[18]

Pharmacologic profile
Molecular target	Binding affinity (K_i in nanomolar)^[19]	Pharmacologic action ^[13]^[15]^[16]^[17]^[20]	Species	Source
SERT	1,000	Inhibitor	Human	Frontal cortex
5-HT_1A	346	Partial agonist	Human	Cloned
5-HT_1B	19.9	Antagonist	Human	Cloned
5-HT_1D	44.3	Antagonist	Human	Cloned
5-HT_1E	1,264	Unknown	Human	Cloned
5-HT_1F	91.6	Unknown	Human	Cloned
5-HT_2A	1,822	Antagonist	Human	Cloned
5-HT_2B	143.7	Antagonist	Human	Cloned
5-HT₇	2,850	Unknown	Human	Cloned
α_1A	1,680	Antagonist	Human	Cloned
α_1B	1,280	Antagonist	Human	Cloned
α_1C	770	Antagonist	Human	Cloned
α_1D	557	Antagonist	Human	Cloned
α_2A	1.05	Antagonist	Human	Cloned
α_2B	1.19	Antagonist	Human	Cloned
α_2C	1.19	Antagonist	Human	Cloned
D₂	339	Antagonist	Human	Cloned
D₃	3,235	Antagonist	Human	Cloned

Research

Sexual dysfunction

Yohimbine has been studied as a potential treatment for erectile dysfunction but there is insufficient evidence to rate its effectiveness.^[6]^[3] 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]

References

^ 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. PMID 1493849. doi:10.1007/BF02284967.
^ yohimbine. (n.d.) Collins English Dictionary – Complete and Unabridged. (1991, 1994, 1998, 2000, 2003). Retrieved January 27, 2015 from http://www.thefreedictionary.com/yohimbine
^ ^a ^b Andersson KE (September 2001). "Pharmacology of penile erection". Pharmacological Reviews. 53 (3): 417–50. PMID 11546836.
^ ^a ^b Beille, P. E. (2013). "Scientific Opinion on the evaluation of the safety in use of Yohimbe (Pausinystalia yohimbe)". EFSA Journal. 11: 3302. doi:10.2903/j.efsa.2013.3302.
^ 21 CFR Sec. 522.2670 Yohimbine
^ ^a ^b "Yohimbe Supplement". National Center for Complementary and Integrative Health. Retrieved 2017-08-28.
^ Kew World Checklist of Selected Plant Families, Pausinystalia johimbe
^ Year Book of the American Pharmaceutical Association. American Pharmaceutical Association. 1914. p. 564. Retrieved 2015-05-04.
^ Witkop, Bernhard (1943). "Zur Konstitution des Yohimbins und seiner Abbauprodukte". Justus Liebig's Annalen der Chemie. 554 (1): 83–126. ISSN 0075-4617. doi:10.1002/jlac.19435540108.
^ Liebig, Justus (1988). The Alkaloids: Chemistry and Pharmacology. Academic Press. p. 564. ISBN 0-12-469532-9.
^ van Tamelen; E. E. (1958). "The Total Synthesis of Yohimbine". J. Am. Chem. Soc. 80: 5006–5007. doi:10.1021/ja01551a062.
^ Herle, B. (2011). "Total Synthesis of (+)-Yohimbine via an Enantioselective Organocatalytic Pictet–Spengler Reaction". J. Org. Chem. 76: 8907–8912. doi:10.1021/jo201657n.
^ ^a ^b ^c 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. PMID 10611634. doi:10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X.
^ "PDSP Ki Database".
^ ^a ^b 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. PMID 8517875. doi:10.1016/0006-2952(93)90208-E.
^ ^a ^b 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. PMID 6136920. doi:10.1007/BF00634263.
^ ^a ^b 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. PMC 1910288 . PMID 8032658. doi:10.1111/j.1476-5381.1994.tb13072.x.
^ "Yohimbine (PIM 567)". Inchem.org. Retrieved 2013-05-26.
^ National Institute of Mental Health. "PDSP Ki Database". University of North Carolina. Archived from the original on November 8, 2013. Retrieved 5 July 2013.
^ "Yohimbine". DrugBank. University of Alberta. Archived from the original on January 30, 2013. Retrieved 12 April 2014.
^ FDA regulations on OTC products
^ 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. PMID 10845761. doi:10.1038/sj.ijir.3900500.

UpToDate Contents

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1. 男性性機能不全の治療 treatment of male sexual dysfunction
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Adamantanes	Adapromine Amantadine Bromantane Memantine Rimantadine
Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline
Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane
Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram
Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine
Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958
Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538
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Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol JZ-IV-10 Modafinil
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Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Ethylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol Hexedrone HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine IMP Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA (midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Ethylbuphedrone N-Ethylhexedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine
Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine
Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP Vanoxerine
Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate Methylphenidate (Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472
Pyrrolidines	2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone
Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide
Tropanes	4-fluorotropacocaine 4'-Fluorococaine Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33
Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT
Others	2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine
ATC code: N06B

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