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.

体外活性：育亨宾（Antagonil）已被用作散瞳剂并用于治疗阳痿。它也被认为是一种春药。育亨宾是一种突触前 α2-肾上腺素能阻断剂。育亨宾可能通过阻断中枢α2-肾上腺素能受体，产生继发于去甲肾上腺素释放和大脑去甲肾上腺素能核细胞放电率增加的交感神经驱动力的增加，从而对勃起能力发挥有益作用。

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Yohimbine 抑制了由亚阈值浓度的肾上腺素（1 μmol/L）和花生四烯酸（0.2 mmol/L）在人富血小板血浆中诱导的协同血小板聚集。
抑制作用呈浓度依赖性，计算得出的IC50值为0.6 μmol/L。[1]

育亨宾可用于创建心脏增强、高血压和神经系统症状的动物模型。

使用双通道发光聚集仪在37°C下监测血小板聚集。
用yohimbine预处理富血小板血浆1分钟。
随后向PRP中加入亚阈值浓度的肾上腺素（1 μmol/L）和花生四烯酸（0.2 mmol/L）以诱导协同聚集。
通过测量透光率的变化，记录5分钟内的聚集过程。
通过构建剂量反应曲线来计算yohimbine的50%抑制浓度（IC50）。[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.

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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

65.56

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)

配方 1 中的溶解度: ≥ 0.5 mg/mL (1.41 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 5.0 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 0.5 mg/mL (1.41 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 5.0 mg/mL 澄清 DMSO 储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 0.5 mg/mL (1.41 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 5.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。