alpha 2-adrenergic receptor

In vitro activity: Yohimbine(Antagonil) has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. 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.

In vitro activity: Yohimbine(Antagonil) has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. 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 inhibited the synergistic platelet aggregation induced by subthreshold concentrations of epinephrine (1 μmol/L) and arachidonic acid (0.2 mmol/L) in human platelet-rich plasma (PRP).
The inhibition was concentration-dependent, with a calculated IC50 value of 0.6 μmol/L.[1]

Yohimbine can be utilized to create animal models of cardiac augmentation, hypertension, and neurological symptoms.

Platelet aggregation was monitored using a dual-channel lumi-aggregometer at 37°C.
Platelet-rich plasma (PRP) was pre-treated with yohimbine for 1 minute.
Subthreshold concentrations of epinephrine (1 μmol/L) and arachidonic acid (0.2 mmol/L) were then added to the PRP to induce synergistic aggregation.
The resulting aggregation was recorded for 5 minutes by measuring the change in light transmission.
Dose-response curves were constructed to calculate the 50% inhibitory concentration (IC50) of yohimbine.[1]

Yohimbine (YO) was freshly dissolved before each experiment by vortexing in sterile 0.15 m NaCl for 5 min at room temperature, followed by passage through a 0.45 μm syringe filter to remove particulate residue. Rats were injected intraperitoneally with 2.0 ml of 0.15 m NaCl vehicle alone, or with vehicle containing YO at a dose of 5.0 mg/kg BW. Injection volumes were adjusted around an average of 2.0 ml per rat to account for small between-animal differences in BW within each experimental cohort. The 5.0 mg/kg BW dose of YO was selected based on recent findings demonstrating that a lower dose of YO (i.e., 1.0 mg/kg BW) did not produce significant effects on food intake, CFA, or central Fos activation (Myers et al., 2005).[J Neurosci . 2006 Nov 1;26(44):11442-53.] Food was removed from cages at 3:30 P.M. (i.e., 3.5 h before dark onset). At 3:00 P.M. on the following day (i.e., 23.5 h later), food-deprived rats (n = 8 DSAP; n = 8 sham control) were injected intraperitoneally with either YO (n = 4 DSAP; n = 4 sham control) or vehicle (n = 4 DSAP; n = 4 sham control). A measured amount of pelleted chow was provided 30 min later, at 3:30 P.M.. Cumulative food intake by each rat, corrected for spillage, was determined after 30 min, 60 min, and 18 h of food access. Rats then were returned to ad libitum chow access for 48 h. The 24 h food deprivation and feeding test was repeated in a counterbalanced design in which rats treated previously intraperitoneally with YO subsequently received vehicle intraperitoneally, and vice versa. Thus, each rat served as its own control for determining the effect of YO on deprivation-induced food intake.[J Neurosci . 2006 Nov 1;26(44):11442-53.]

Absorption, Distribution and Excretion
Absorbed rapidly after oral administration. Bioavailability varies considerably, ranging from 7% to 87% (mean 33%). 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. Biological Half-Life Elimination half-life is approximately 36 minutes.

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 weight-loss and muscle-building herbal combinations, it has not been found to be associated with clinically significant cases of acute liver injury. Probability Score: E (Unlikely a cause of clinically significant liver injury). Drug Category: Herbal and Dietary Supplements

[1]. Saeed SA, et al. Signaling mechanisms mediated by G-protein coupled receptors in human platelets. Acta Pharmacol Sin. 2004 Jul;25(7):887-892.
[2]. Blanchard RJ, et al. Yohimbine potentiates active defensive responses to threatening stimuli in Swiss-Webster mice. Pharmacol Biochem Behav. 1993 Mar;44(3):673-681.
[3]. Fuller BB, et al. Downregulation of tyrosinase activity in human melanocyte cell cultures by yohimbine. J Invest Dermatol. 2000 Feb;114(2):268-276.

Yohimbine is an indole alkaloid with α2-adrenergic receptor antagonistic activity. It is produced from the African neem tree (Corynanthe johimbe) and the snake root tree (Rauwolfia serpentina). It functions as an α-adrenergic antagonist, a serotonergic antagonist, and a dopamine D2 receptor antagonist. Its function is related to yohimbine acid. Yohimbine is a plant alkaloid with α2-adrenergic blocking activity. It has been used as a mydriatic and to treat impotence. It is also believed to have aphrodisiac effects. Yohimbine is an indole alkaloid extracted from the bark of the Central African yohimbine tree (Pausinystalia yohimbe) and is widely used to treat erectile dysfunction. The use of yohimbine has been associated with occasional serious adverse events, but has not been found to be associated with elevated serum enzymes or clinically significant acute liver injury.
Yohimbine has been reported to exist in Rauvolfia yunnanensis, Rauvolfia serpentina, and other organisms with relevant data.
Yohimbine is a plant alkaloid with α2-adrenergic blocking activity. It has been used as a mydriatic and to treat erectile dysfunction.
See also: Yohimbine hydrochloride (salt form)...see more...
Pharmacological Indications

Used as a sympathomimetic and mydriatic. Yohimbine has been successfully used to treat vascular, diabetic, or psychogenic erectile dysfunction in men.
Mechanism of Action

Yohimbine is a presynaptic α2-adrenergic blocker. The exact mechanism of its treatment of erectile dysfunction has not been fully elucidated. However, yohimbine may improve erectile function by blocking central α2-adrenergic receptors, thereby increasing norepinephrine release and the firing frequency of norepinephrine nuclei in the brain, thus enhancing sympathetic nerve excitation. Yohimbine-mediated norepinephrine release from the corpus cavernosum may also be involved. Furthermore, its beneficial effects may involve other neurotransmitters, such as dopamine and serotonin, as well as cholinergic receptors.

---

Pharmacodynamics
Yohimbine is an indolealkylamine alkaloid with a chemical structure similar to reserpine. Yohimbine blocks presynaptic α2-adrenergic receptors. Its effects on peripheral blood vessels are similar to reserpine, but weaker and shorter-lasting. Yohimbine's effect on the peripheral autonomic nervous system is to enhance parasympathetic (cholinergic) activity and decrease sympathetic (adrenergic) activity. It is noteworthy that, in terms of male sexual function, erection is associated with cholinergic activity and α2-adrenergic receptor blockade, which theoretically could lead to increased penile blood flow, decreased penile blood flow, or both. Yohimbine has a mood-stimulating effect and may exacerbate anxiety. Although these effects appear to require high doses, they have not been adequately studied or dose-related. Yohimbine has a mild antidiuretic effect, likely mediated by stimulation of the hypothalamus and release of posterior pituitary hormones. Yohimbine has been reported to have no significant effect on cardiac stimulation and other effects mediated by β-adrenergic receptors. Its effect on blood pressure, if any, is to lower blood pressure; however, there are currently insufficient studies to quantify the effect of yohimbine doses on blood pressure. In this study, yohimbine was used as a pharmacological tool to block α2-adrenergic receptors on human platelets. Its inhibitory effect suggests that synergistic platelet aggregation between adrenaline and arachidonic acid is mediated by α2-adrenergic receptor activation. [1]

C21H26N2O3

354.45

354.194

C, 71.16; H, 7.39; N, 7.90; O, 13.54

146-48-5

Yohimbine-13C,d3;1261254-59-4;Yohimbine-d3;133146-00-6;Yohimbine Hydrochloride;65-19-0

8969

Typically exists as solid at room temperature

1.3±0.1 g/cm3

543.0±50.0 °C at 760 mmHg

231-233 °C(lit.)

282.2±30.1 °C

0.0±1.5 mmHg at 25°C

1.661

2.2

2

4

2

26

555

5

[H][C@]12C(NC3=C4C=CC=C3)=C4CCN1C[C@@]5(CC[C@H](O)[C@H](C(OC)=O)[C@]5(C2)[H])[H]

BLGXFZZNTVWLAY-SCYLSFHTSA-N

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

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~5 mg/mL (~14.11 mM)
H2O : ~1 mg/mL (~2.82 mM)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.41 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 5.0 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.

---

Solubility in Formulation 2: ≥ 0.5 mg/mL (1.41 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 5.0 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.

---

View More

Solubility in Formulation 3: ≥ 0.5 mg/mL (1.41 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 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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