Yohimbine HCl (Antagonil; Corynine; Quebrachin; Quebrachine; Yohimex; Yocon; APHRODINE; Aphrodyne; Aphrosol; Johimbin), the hydrochloride salt of Yohimbine, is a potent alpha 2-adrenoreceptor antagonist used as a mydriatic for the treatment of impotence. It is an indole alkaloid derived from the bark of the Pausinystalia yohimbe tree in Central Africa. Yohimbine is also alleged to be an aphrodisiac. 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.

Physicochemical Properties

Molecular Formula	C21H26N2O3.HCL
Molecular Weight	390.9
Exact Mass	390.171
Elemental Analysis	C, 64.52; H, 6.96; Cl, 9.07; N, 7.17; O, 12.28
CAS #	65-19-0
Related CAS #	Rauwolscine hydrochloride; 6211-32-1; Yohimbine; 146-48-5; Rauwolscine; 131-03-3
PubChem CID	6169
Appearance	White to light yellow solid powder
Boiling Point	542.979ºC at 760 mmHg
Melting Point	288-290 °C (dec.)(lit.)
Flash Point	282.184ºC
Index of Refraction	103 ° (C=1, H2O)
LogP	3.387
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	27
Complexity	555
Defined Atom Stereocenter Count	5
SMILES	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]
InChi Key	PIPZGJSEDRMUAW-VJDCAHTMSA-N
InChi Code	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
Chemical Name	methyl (1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate;hydrochloride
Synonyms	Antagonil; Yohimbine; Yohimbin; Corynine; Quebrachin; Quebrachine; Yohimex; Yocon; APHRODINE; (+)-Yohimbine; Aphrodyne; Aphrosol; Antagonil; Yohimbe; Aphrodine hydrochloride; Yohimbine monohydrochloride; Yohimbin HCl; Johimbin; Yohimbic acid methyl ester; Actibine; Thybine; Yohimar; Yovital; Yoman; Dayto himbin
HS Tariff Code	2934.99.9001
Storage	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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	alpha 2-adrenergic receptor
ln Vitro	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]
ln Vivo	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]. 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.
Animal Protocol	yohimbine (YO) preparation and administration [2] 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).[2] Effect of DSAP lesions on the ability of yohimbine (YO) to inhibit food intake. [2] 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.[2] 0.2 mg/kg, i.p. Rats
ADME/Pharmacokinetics	Absorption Rapidly absorbed following oral administration. Bioavailability is highly variable, ranging from 7 to 87% (mean 33%). Metabolism / Metabolites Yohimbine appears to undergo extensive metabolism in an organ of high flow such as the liver or kidney, however, the precise metabolic fate of yohimbine has not been fully determined. Biological Half-Life Elimination half-life is approximately 36 minutes.
Toxicity/Toxicokinetics	rat LD50 intraperitoneal 55 mg/kg Hepatotoxicity In small clinical trials and case series, yohimbine therapy has not been linked to serum enzyme elevations or clinical liver disease. Although yohimbine is often found in weight loss and muscle building herbal combinations, it has not been associated with cases of clinically apparent acute liver injury.br> Likelihood score: E (unlikely cause of clinically apparent liver injury).
References	[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.
Additional Infomation	A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION. See also: Yohimbine (has active moiety).

Solubility Data

Solubility (In Vitro)

DMSO: 12~33.3 mg/mL (30.7~85.3 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5582 mL	12.7910 mL	25.5820 mL
	5 mM	0.5116 mL	2.5582 mL	5.1164 mL
	10 mM	0.2558 mL	1.2791 mL	2.5582 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.