146-48-5 Usage
Uses
Used in Pharmaceutical Industry:
17alpha-Hydroxy-yohimban-16alpha-carboxylic acid methyl ester is used as an adrenergic blocking agent for the treatment of sexual dysfunction. It acts primarily as an antagonist at α2-adrenergic receptors, which helps in the management of erectile dysfunction.
Used in Veterinary Medicine:
17alpha-Hydroxy-yohimban-16alpha-carboxylic acid methyl ester has been used as an aphrodisiac in veterinary medicine, where it has shown potential in treating impotence and paralytic insensitivity caused by neurasthenia.
Physical Properties:
Appearance: White powder
Solubility: Soluble in ethanol, chloroform, and hot benzene; slightly soluble in water and ether. It is usually salified by hydrochloric acid to increase its solubility in water.
Specific rotatory power (°): D22 +105° (in water)
Melting point: 241–246°C
Chemical Properties:
17alpha-Hydroxy-yohimban-16alpha-carboxylic acid methyl ester is a glistening, needle-like alkaloid, soluble in alcohol and ether, and very slightly soluble in water.
Overview Information
Yohimbe is the name of an evergreen tree found in parts of central and western Africa. The bark of yohimbe contains a chemical called yohimbine, which is used to make medicine. Yohimbine hydrochloride (Aphrodyne, Yocon) is a form of yohimbine that is a prescription drug in the US.
Yohimbe supplements often list yohimbe bark extract or yohimbine as the active ingredient. However, some of these products might not provide accurate information about the amount of yohimbine in the supplement. Also, some yohimbe supplements list yohimbine hydrochloride as an active ingredient. Yohimbe products containing man-made yohimbine hydrochloride as an ingredient are not legal to sell as a dietary supplement in the US.
Yohimbe is taken by mouth arouse sexual excitement, for erectile dysfunction (ED), sexual problems caused by medications for depression called selective-serotonin reuptake inhibitors (SSRIs), and general sexual problems in both men and women. It is also used for athletic performance, weight loss, exhaustion, chest pain, high blood pressure, low blood pressure that occurs when standing up, diabetic nerve pain, and for depression along with certain other medications.
Effectiveness
Anxiety. There is mixed evidence about the effectiveness of yohimbine, the active ingredient in yohimbe, for treating anxiety related to phobias. Some research suggests that it does not improve anxiety when combined with therapy. However, other research suggests that it reduces fear related to certain phobias.
Depression. Early research suggests that taking yohimbine, the active ingredient of yohimbe, daily for 10 days does not improve depression symptoms.
Erectile dysfunction (ED). There is evidence that yohimbine, the active ingredient of yohimbe, can be helpful for ED. Some herbalists suggest that the yohimbe bark actually works better than the yohimbine ingredient alone. However, so far yohimbe bark has not been evaluated in research studies.
Exercise performance. Early research suggests that taking yohimbine, the active ingredient in yohimbe, daily for 21 days does not improve exercise performance or build muscle mass in soccer players.
Head rush (orthostatic hypotension). Early research suggests that taking a single dose of yohimbine, the active ingredient in yohimbe, increases blood pressure in people with a head rush due to low blood pressure. However, other early research suggests that it does not improve blood pressure.
Sexual problems caused by selective-serotonin reuptake inhibitors (SSRIs). There is evidence from many studies that yohimbine, the active ingredient of yohimbe, can improve sexual problems associated with this class of medications used for depression. However, this benefit has not been described specifically for the yohimbe bark.
Dry mouth. Early research suggests that taking yohimbine, the active ingredient in yohimbe, improves symptoms of dry mouth in people taking antidepressants. The effect of the yohimbe bark on dry mouth is not clear.
Side Effects
Yohimbe, taken by mouth, is POSSIBLY UNSAFE. Yohimbe has been linked to reports of severe side effects including irregular or rapid heart beat, kidney failure, seizure, heart attack, and others.
The primary active ingredient in yohimbe is a drug called yohimbine. This is considered a prescription drug in North America. This drug can be safely used short-term when monitored by a health professional.
However, it is not appropriate for unsupervised use due to potentially serious side effects that it can cause.
Children should not take yohimbe. It is POSSIBLY UNSAFE for children because children appear to be extra sensitive to the harmful effects of yohimbe.
When taken by mouth in typical doses, yohimbe and the ingredient yohimbine can cause stomach upset, excitation, tremor, sleep problems, anxiety or agitation, high blood pressure, a racing heartbeat, dizziness, stomach problems, drooling, sinus pain, irritability, headache, frequent urination, bloating, rash, nausea, and vomiting.
Taking high doses can also cause other severe problems, including difficulty breathing, paralysis, very low blood pressure, heart problems, and death. After taking a one-day dose of yohimbine, one person reported an allergic reaction involving fever; chills; listlessness; itchy, scaly skin; progressive kidney failure; and symptoms that looked like the auto-immune disease called lupus.
History
Yohimbine has been used as an aphrodisiac for many years. At first, pharmacologists attributed its aphrodisiac effects to psychological effects similar to placebo or
increasement of peripheral vascular congestion, rather than real sexual stimulation.
Physiologists at the Stanford University first conducted a study on the pharmacological effects of yohimbine and found that yohimbine could increase the mating
ability of rats , which was then published on Science in 1984 . In addition,
researchers in the Queensland University in Canada conducted experiments on 23
patients with sexual dysfunction. Six of them recovered after taking the drug for
10?weeks. In 1987, Canadian scientists confirmed that yohimbine treatment in psychogenic impotence was safe and effective and this drug could restore the patient’ssexual ability . Besides, they proved that this medicine showed good curative
effects on organic impotence.
Indications
This product is listed in the 2017 edition of the British Pharmacopoeia, 40 editions
of the American Pharmacopoeia, and 9.0 edition of the European Pharmacopoeia.
The main clinical application of yohimbine includes tablets and injections. It is
mainly used to treat various types of impotence and sexual dysfunction in men.
Health Hazard
Pharmacologically, yohimbine is an adrenergic blocking agent. It exhibits hypotensive and cardiostimulant activities. Poisoningfrom excessive doses may become severe,causing convulsions and respiratory failureLD50 value, intraperitoneal (mice): 16 mg/kgLD50 value, oral (mice): 37 mg/kg.
Biological Activity
α 2 -adrenoceptor antagonist (pK i values are 8.52, 8.00 and 9.17 for human a 2A , a 2B and a 2C receptors respectively).
Pharmacology
Studies have shown that yohimbine has extensive pharmacological effects and has
been developed for the clinical treatment of arteriosclerosis, rheumatism, and other
diseases. The most obvious pharmacological action is in the treatment of male sexual dysfunction. Yohimbine tablets have been approved by the FDA and circulate in
international markets. Yohimbine can selectively block the presynaptic alpha 2
receptors and promote the release of norepinephrine . It stimulates more norepinephrine released by cavernous nerve endings and reduces reflux of phallic vein,
which is conducive to congestive erection. A small amount of application can make
the perineum swell and stimulate the erection center at the spinal cord, leading to
sexual hyperfunction . Yohimbine hydrochloride also has a psychological stimulant effect and increases libido. Like other types of adrenergic blocking drugs,
yohimbine’s resistance to adrenergic mediator in blood circulation is much stronger
than to sympathetic nerve impulse. Again, like tolazoline, yohimbine shows slight
effect in resisting adrenergic response in ocular smooth muscle. This drug does not
block the frequency and inotropic effects of epinephrine on mammalian hearts.
Yohimbine has minor direct effects on smooth muscle, and its effect on the central
nervous system is far less than that of ergot alkaloids, because yohimbine performs
an excited-to-paralyzed action. This drug produces diuretic effect, probably due to
the stimulation of the hypothalamus, resulting in release of posterior pituitary hormone. In addition, yohimbine has a significant local anesthetic effect .
Clinical Use
Yohimbine increases heart rate and blood pressure as aresult of its blockade of 2-receptors in the CNS. It has beenused experimentally to treat male erectile impotence.
Purification Methods
Crystallise the alkaloid from EtOH, and dry it in a vacuum to remove EtOH of crystallisation. [Van Tamelen et al. J Am Chem Soc 91 7315 1969, Stork
Check Digit Verification of cas no
The CAS Registry Mumber 146-48-5 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,4 and 6 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 146-48:
(5*1)+(4*4)+(3*6)+(2*4)+(1*8)=55
55 % 10 = 5
So 146-48-5 is a valid CAS Registry Number.
InChI:InChI=1/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
146-48-5Relevant articles and documents
Indole alkaloids and other constituents of Rauwolfia serpentina
Itoh, Atsuko,Kumashiro, Tomoko,Yamaguchi, Machiko,Nagakura, Naotaka,Mizushina, Yoshiyuki,Nishi, Toyoyuki,Tanahashi, Takao
, p. 848 - 852 (2005)
From the dried roots of Rauwolfia serpentina were isolated five new indole alkaloids, Nb-methylajmaline (1), Nb-methylisoajmaline (2), 3-hydroxysarpagine (3), yohimbinic acid (4), isorauhimbinic acid (5), a new iridoid glucoside, 7-epiloganin (6), and a new sucrose derivative, 6′-O-(3,4,5-trimethoxybenzoyl)glomeratose A (7), together with 20 known compounds. The structures of the new compounds were determined by spectroscopic and chemical means. The inhibitory activities of the selected alkaloids on topoisomerase I and II and their cytotoxicity against the human promyelocytic leukemia (HL-60) cell lines were assessed.
Microwave-enhanced, stereospecific ring-closure of medium-ring cyanamide ethers to yohimbine
Paciaroni, Nicholas G.,Norwood, Verrill M.,Garcia, Daniel E.,Huigens, Robert W.
, p. 1182 - 1185 (2019)
A highly efficient acid-promoted, stereospecific, transannular ring-closure of medium-ring ether compounds to the indole alkaloid yohimbine is described. Microwave-enhanced acetic acid degradation of cyanamide compounds involves loss of (R)- or (S)-ethers, followed by a stereospecific, nucleophilic ring-closure from the cyanamide to afford yohimbine in up to 74% yield in as little as one minute. This nucleophilic reactivity of the amino moiety of the cyanamide highlights an alternative reactivity profile from its traditional electrophilic properties. Additionally, this reaction pathway highlights a rare case of an SN1 pathway that proceeds with complete stereospecificity.
Total synthesis of (+)-yohimbine via an enantioselective organocatalytic Pictet-Spengler reaction
Herle, Bart,Wanner, Martin J.,Van Maarseveen, Jan H.,Hiemstra, Henk
, p. 8907 - 8912 (2011/12/21)
The binolphosphoric acid-catalyzed Pictet-Spengler reaction of an N-(5-oxy-2,4-pentadienyl)tryptamine derivative with methyl 5-oxo-2- (phenylseleno)pentanoate leads to the tetrahydro-β-carboline in a 92:8 enantiomeric ratio. This product is easily converted into the substrate for a stereoselective intramolecular Diels-Alder reaction of the type earlier reported by Jacobsen. These two key steps constitute the basis for a nine-step total synthesis of (+)-yohimbine from tryptamine. A similar asymmetric Pictet-Spengler reaction was applied to the synthesis of an intermediate in the recent total synthesis of corynantheidine by Sato.
Compounds and compositions for treating infection
-
, (2009/04/24)
Compounds from 14 Kenyan plants, including from the root of Dovyalis abyssinica and Clutia robusta have been characterized and isolated, and their uses are disclosed.
THERAPY FOR COMPLICATIONS OF DIABETES
-
, (2009/07/02)
A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
ANTIHYPERTENSIVE THERAPY
-
, (2009/09/08)
A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
Catalytic asymmetric total synthesis of (+)-yohimbine
Mergott, Dustin J.,Zuend, Stephan J.,Jacobsen, Eric N.
supporting information; experimental part, p. 745 - 748 (2009/04/06)
The total synthesis of (+)yohimbine was achieved in 11 steps and 14% overall yield. The absolute configuration was established through a highly enantioselective thiourea-catalyzed acyl-Pictet-Spengler reaction, and the remaining 4 stereocenters were set simultaneously in a substrate-controlled intramolecular Diels Alder reaction.
Method for treating resistant hypertension
-
, (2008/06/13)
A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.
Enantiospecific synthesis of (-)-3-iso-19,20-dehydro-β-yohimbine from secologanin: A route to normal and pseudo stereoisomers of yohimbine
Brown, Richard T.,Pratt, Simon B.,Richards, Paul
, p. 5627 - 5630 (2007/10/03)
Hydrolysis of secologanin ethylene acetal at pH 7 resulted in stereoselective aldol cyclisation to a cyclohexene aldehyde, which, on reductive amination and cyclisation with tryptamine afforded (-)-3-iso-19,20- dehydro-β-yohimbine, converted into various normal and pseudo isomers of yohimbine. (C) 2000 Elsevier Science Ltd.
Biomimetic synthesis of monoterpenoid indole alkaloids from aglucones of secologanin derivatives: pH controlled product selectivity
Brown
, p. 609 - 616 (2007/10/03)
Variation of the pH for hydrolysis of secologanin derivatives with β-glucosidase controls rearrangement of the aglucone to afford different products, and hence stercoselective syntheses of heteroyohimbine, yohimbine and Aspidosperma-type alkaloids; with baker's yeast chemoselective reduction can also be achieved to give a precursor for antirhine and related alkaloids.
