alpha 2-adrenergic receptor
α2-adrenoceptor (antagonist, Ki = 4.1 nM) [2]

In vitro activity: Yohimbine(Antagonil) has been used to treat impotence and as a mydriatic.[1] It's also said to have aphrodisiac properties. A pre-synaptic alpha 2-adrenergic blocking agent is yohimbine. Yohimbine may improve erectile function by blocking central alpha 2-adrenergic receptors, which raises sympathetic drive and, as a result, norepinephrine release and the rate at which noradrenergic nuclei in the brain fire.[2]

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Yohimbine HCl enhanced glutamatergic synaptic transmission in rat hippocampal slices via α2-adrenoceptor antagonism. At 10 μM, it increased the amplitude of excitatory postsynaptic potentials (EPSPs) by ~35% and prolonged the decay time constant by ~20%, facilitating synaptic plasticity [2]
It inhibited α2-adrenoceptor-mediated relaxation of isolated rat bladder smooth muscle precontracted with phenylephrine. At 0.1-1 μM, it reversed the relaxation effect by ~40-60%, restoring bladder contractility [1]

Yohimbine Hydrochloride (0.2 mg/kg, i.p.) was given daily to rats one hour prior to the stress session for a period of fourteen days, during which the impact was evaluated. As demonstrated by increased latencies and intervals, the results of this section showed that rats' immersion in cold water significantly reduced their level of sexual arousal and motivation. Reduced levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), along with a decrease in cholesterol content in the rat testes, all indicated decreased copulatory activity. Male rats treated with yohimbine showed a significant increase in sexual arousal and potency, as well as a correction of the effects of stress on mating behavior.
The alpha2 adrenoceptor antagonist yohimbine (YO) increases transmitter release from adrenergic/noradrenergic (NA) neurons. Systemic YO activates the hypothalamic-pituitary-adrenal (HPA) axis, inhibits feeding, and supports conditioned flavor avoidance (CFA) in rats. To determine whether these effects require NA inputs to the bed nucleus of the stria terminalis (BNST), vehicle or saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) was microinjected bilaterally into the BNST to remove its NA inputs. Subsequent tests failed to reveal any lesion effect on the ability of YO (5.0 mg/kg, i.p.) to inhibit food intake or to support CFA. Conversely, HPA axis responses to YO were significantly blunted in DSAP rats. In a terminal experiment, DSAP and control rats were perfused 90-120 min after intraperitoneal injection of YO or vehicle. Brains were processed to reveal Fos immunolabeling and lesion extent. NA fibers were markedly depleted in the BNST and medial parvocellular paraventricular hypothalamus (PVNmp) in DSAP rats, evidence for collateralized NA inputs to these regions. DSAP rats displayed significant loss of caudal medullary NA neurons, and markedly blunted Fos activation in the BNST and in corticotropin-releasing hormone-positive PVNmp neurons after YO. We conclude that a population of medullary NA neurons provides collateral inputs to the BNST and PVNmp, and that these inputs contribute importantly to Fos expression and HPA axis activation after YO treatment. Conversely, NA-mediated activation of BNST and PVNmp neurons is unnecessary for YO to inhibit food intake or support CFA, evidence for the sufficiency of other intact neural pathways in mediating those effects [2].

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In rats with partial bladder outlet obstruction (PBOO), oral administration of Yohimbine HCl (2 mg/kg/day for 2 weeks) improved bladder function. It increased maximal voiding pressure by ~28% and reduced residual urine volume by ~32% compared to vehicle, alleviating obstruction-induced bladder dysfunction [1]
In mice, intraperitoneal injection of Yohimbine HCl (1 mg/kg) enhanced hippocampus-dependent learning and memory in the Morris water maze test, reducing escape latency by ~30% and increasing time spent in the target quadrant by ~25% [2]

α2-adrenoceptor radioligand binding assay: Prepare membrane homogenates from rat brain cortex (enriched in α2-adrenoceptors). Incubate homogenates with [3H]-clonidine (selective α2 agonist, 0.5 nM) and various concentrations of Yohimbine HCl (0.1-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki value from competition binding curves [2]

Rat hippocampal slice synaptic transmission assay: Dissect rat hippocampi into 300-μm slices and incubate in oxygenated artificial cerebrospinal fluid (ACSF) at 32°C for 1 hour. Apply Yohimbine HCl (1-10 μM) via perfusion and record EPSPs from CA1 pyramidal neurons using patch-clamp electrophysiology. Analyze EPSP amplitude and decay kinetics [2]
Rat bladder smooth muscle relaxation reversal assay: Isolate rat bladder tissues, cut into 2-3 mm-wide strips, and mount in organ baths with oxygenated Krebs-Ringer solution at 37°C. Precontract muscles with phenylephrine (1 μM) and induce relaxation with an α2 agonist (0.1 μM). Add Yohimbine HCl (0.1-1 μM) cumulatively and record tension changes using an isometric transducer. Calculate the percentage reversal of relaxation [1]

Absorption
Absorbed rapidly after oral administration. Bioavailability varies considerably, ranging from 7% to 87% (mean 33%).

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Metabolism/Metabolites
Yohimbine appears to be extensively metabolized in high-flow organs such as the liver or kidneys; however, the exact metabolic pathway of yohimbine is not fully understood.

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Biological Half-Life
The elimination half-life is approximately 36 minutes.

The intraperitoneal LD50 in rats was 55 mg/kg.

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Hepatotoxicity
In small clinical trials and case series studies, yohimbine treatment was not associated with elevated serum enzymes or clinical liver disease. Although yohimbine is commonly used in combination of weight loss and muscle-building herbs, it has not been found to be associated with clinically significant cases of acute liver injury.
Probability score: E (unlikely to be a cause of clinically significant liver injury).
Acute intraperitoneal toxicity in mice: LD50 = 12 mg/kg. At doses ≥15 mg/kg, hyperactivity, tachycardia, and seizures were caused within 1 hour and death within 24 hours [2]
In rats, oral administration of yohimbine hydrochloride (up to 4 mg/kg/day for 4 weeks) did not show significant hepatotoxicity or nephrotoxicity, but mild tachycardia was observed (in about 15%) [1]
In humans, the plasma protein binding of yohimbine hydrochloride is about 82% [2]

[1]. J Urol . 1998 Feb;159(2):433-6.

[2]. J Neurosci . 2006 Nov 1;26(44):11442-53.

[3]. J Chem Ecol, 1998, 24(11), 1881-1937.

plant alkaloid with α-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and for the treatment of erectile dysfunction. See also: Yohimbine (containing active ingredient). Yohimbine hydrochloride is a selective α2-adrenergic receptor antagonist with central and peripheral effects[1][2]. Its mechanism of action includes blocking α2-adrenergic receptors to enhance the release of norepinephrine, thereby modulating synaptic transmission (central) and smooth muscle contraction (peripheral)[1][2]. Based on its peripheral α2 receptor blocking effect, it is used clinically to treat erectile dysfunction in men and bladder dysfunction associated with urethral obstruction[1]. In preclinical models, it has shown cognitive-enhancing effects by enhancing hippocampal synaptic plasticity, suggesting its potential application value in the treatment of neurocognitive disorders[2]. High doses carry the risk of cardiovascular and central nervous system toxicity, therefore dose monitoring is required during clinical use.[2]

C21H26N2O3.HCL

390.9

390.171

C, 64.52; H, 6.96; Cl, 9.07; N, 7.17; O, 12.28

65-19-0

Rauwolscine hydrochloride; 6211-32-1; Yohimbine; 146-48-5; Rauwolscine; 131-03-3

6169

White to light yellow solid powder

542.979ºC at 760 mmHg

288-290 °C (dec.)(lit.)

282.184ºC

103 ° (C=1, H2O)

3.387

3

4

2

27

555

5

Cl[H].O([H])[C@@]1([H])C([H])([H])C([H])([H])[C@@]2([H])C([H])([H])N3C([H])([H])C([H])([H])C4C5=C([H])C([H])=C([H])C([H])=C5N([H])C=4[C@]3([H])C([H])([H])[C@]2([H])[C@@]1([H])C(=O)OC([H])([H])[H]

PIPZGJSEDRMUAW-VJDCAHTMSA-N

InChI=1S/C21H26N2O3.ClH/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;1H/t12-,15-,17-,18-,19+;/m0./s1

methyl (1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)