Guanethidine was not shown to significantly affect the survival of endothelial cells and mesenchymal stem cells in vitro, but it was linked to the loss of endothelial cell markers (RECA) in rats following sympathetic fiber ablation [1].

In TNFR1(-/-) mice, guanetidine (30 mg/kg, subcutaneous injection, 1 hour) does not interfere with IL-18-induced increased nociception [2].

Animal/Disease Models: wild-type (WT) Balb/c, TNFR1 (-/-) and IFN-γ-γ (-/-) mice [2].
Doses: 30 mg/kg
Route of Administration: Guanetidine (30 mg/kg, SC, 1 hour, diluted in saline)
Experimental Results: Pretreatment with guanethidine (sympatholytic agent) did not affect TNFR1(-/ -) IL-18-excessive nociception in mice.

Absorption, Distribution and Excretion
3-30% of the oral dose (low and highly variable absorption) Ismeridine is converted into three metabolites in the liver and excreted in the urine. Renal clearance = 56 ml/min …In mice, 30 minutes after intraperitoneal injection of the antihypertensive drug [(14)C]-guanethidine, most of the [(14)C] was distributed in the liver, gastrointestinal tract, spleen, kidneys, bladder, salivary glands, and brown adipose tissue. In rats, plasma drug concentrations were lower than tissue concentrations 1-2 hours after intraperitoneal injection. In human subjects treated with guanethidine, 24% of [(14)C] was excreted in the urine 24 hours after oral administration, and 52% after intravenous administration. Excretion of [(14)C] is ongoing; approximately half of the drug excreted within 24 hours remains in the urine after 48 hours. Following oral administration, approximately 23% is excreted in feces within 72 hours; following intravenous administration, approximately 3% is excreted. In subjects with hypertension, most intravenously administered [(3)H]guanethidine is excreted unchanged in urine; excretion is slower in subjects with concurrent renal failure. …After systemic administration, the drug has very poor penetration into the central nervous system. Guanethidine is absorbed and stored by adrenergic nerves, and this accumulation is crucial for its efficacy. For more complete data on the absorption, distribution, and excretion of guanethidine (a total of 6 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
Guetidine is converted into three metabolites in the liver, which are excreted in urine. The pharmacological activity of the metabolites is lower than that of the parent compound. Metabolism appears to occur via hepatic microsomal enzymes, with a significantly higher rate of metabolism after oral administration than after parenteral administration. …In humans, significant N-oxidation occurs on the tertiary nitrogen atom on the perhydroazocyclooctane ring.
When patients with low blood pressure take guanethidine, the drug is excreted unchanged via the kidneys, along with guanethidine N-oxide and 2-(6-carboxyhexano)-ethylguanidine.

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Biological half-life
1.5 days
...Guetidine...binds to plasma proteins and tissues, resulting in a half-life extended by approximately 30 hours.

Interactions
Monoamine oxidase inhibitors have been reported to antagonize the hypotensive effect of guanethidine. Topical application of guanethidine can enhance the ocular response to topical phenylephrine, leading to increased mydriasis. Thiazide drugs can enhance the hypotensive effect of guanethidine, thereby reducing the dosage of guanethidine and decreasing the incidence of adverse reactions… Dextroamphetamine and its related compounds can block the hypotensive effect of guanethidine; therefore, concomitant use of these drugs should be avoided. For more complete data on interactions of guanethidine (10 in total), please visit the HSDB records page.

[1]. P Dubový, etal. Local chemical sympathectomy of rat bone marrow and its effect on marrow cell composition.

[2]. Waldiceu A.VerriJr, etal. Antigen-induced inflammatory mechanical hypernociception in mice is mediated by IL-18. Brain Beha.

Guanethidine is a guanidine compound in which a hydrogen atom on the amino group is replaced by a 2-azacyclohexane-1-ylethyl group. It possesses pharmacological effects including antihypertensive, adrenergic antagonist, and sympathetic blocking. It belongs to the guanidine and azacyclohexane classes, functionally related to guanidine compounds, and is derived from the hydride of azacyclohexane. It is an antihypertensive drug that works by selectively inhibiting postganglionic adrenergic neurotransmission. The main mechanism of action of guanethidine is believed to be the inhibition of norepinephrine release from nerve endings, leading to depletion of norepinephrine in peripheral sympathetic nerve endings and tissues. Indications: Used to treat moderate to severe hypertension, either alone or as adjunctive therapy, and also for the treatment of renal hypertension.

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Mechanism of Action
Guetidine does not act on effector cells by inhibiting the binding of norepinephrine to its receptors. Instead, it acts at the sympathetic effector junction by inhibiting or interfering with the release and/or distribution of norepinephrine (NE). It is taken up by norepinephrine transporters and displaces NE within neurotransmitter vesicles, leading to the gradual depletion of NE stores in nerve endings. Guanetidine blocks action potential-induced norepinephrine release at nerve endings. Unlike ganglion blockers, guanetidine has the same inhibitory effect on α- and β-adrenergic receptor-mediated responses but does not cause parasympathetic blockade. Because sympathetic blockade leads to a slight decrease in peripheral resistance and cardiac output, guanetidine lowers blood pressure in the supine position. It can further lower blood pressure because it reduces the degree of vasoconstriction caused by reflex sympathetic activity in the upright position, thereby further reducing venous return and cardiac output.
Guetidine can be considered a representative drug for inhibiting postganglionic adrenergic nerve function.
Rapid intravenous injection…can cause…an initial rapid drop in blood pressure, accompanied by an increase in cardiac output and a decrease in peripheral resistance; the latter is likely due to the drug’s transient direct effect on resistance vessels. Hypertension develops after the drop in blood pressure…
Main action…inhibits the response of sympathomimetic amines to the activation and indirect effects of sympathoadrenergic nerves. Since guanethidine also sensitizes effector cells to catecholamines, effective blockade necessarily means a significant reduction in the amount of mediators released. It has significant local anesthetic activity…
Guetidine apparently accumulates in intraneuronal storage granules and replaces norepinephrine, and it is also released itself upon neural stimulation. Therefore, it fits the definition of a “pseudo-neurotransmitter,” but this mechanism does not appear to be the cause of its action.
For more complete data on the mechanisms of action of guanethidine (7 types), please visit the HSDB record page.

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Therapeutic Uses
Adrenergic drugs; antihypertensive drugs; sympathetic nerve blockers
Guetidine's primary use is limited to the treatment of hypertension… It is also effective in controlling hypertensive episodes associated with high spinal cord injury. Topical application of guanetidine has been limited in the treatment of glaucoma… and is used to treat Horner's syndrome caused by abnormal eyelid retraction.
Guetidine… can be used as an adjunct to antithyroid drugs in the treatment of hyperthyroidism and thyroid storm.
Guetidine… has been used in eye drops to lower intraocular pressure in glaucoma patients and reduce eyelid retraction caused by thyroid disease.
For more complete data on the therapeutic uses of guanetidine (6 types), please visit the HSDB record page.

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Drug Warnings
Guetidine inhibits cardiovascular reflexes…increased gastrointestinal motility…water and sodium retention…may be related to hemodynamic effects…
Guetidine’s sensitization to sympathomimetic drugs found in some “cold medicines” can lead to hypertensive crisis.

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Pharmacodynamics
High blood pressure can cause abnormal heart and arterial function. This can damage blood vessels in the brain, heart, and kidneys, leading to stroke, heart failure, or kidney failure. High blood pressure can also increase the risk of heart attack. If blood pressure is controlled, the likelihood of these problems occurring is reduced. Guanethidine works by lowering heart rate and relaxing blood vessels, making it easier for blood to flow through the body, thus reducing these risks. It is a postganglionic sympathetic nerve ending blocker that prevents the release of norepinephrine from nerve endings.

C10H22N4

198.314

198.184

55-65-2

Guanethidine sulfate;645-43-2

3518

Typically exists as solid at room temperature

1.13g/cm3

345.6ºC at 760mmHg

276-281
250 °C (sulfate salt)

162.8ºC

1.4910 (estimate)

1.864

2

2

3

14

167

0

C1CCCN(CCC1)CCNC(=N)N

ACGDKVXYNVEAGU-UHFFFAOYSA-N

InChI=1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)

2-[2-(azocan-1-yl)ethyl]guanidine

Dopam; Octatensine; Guanethidine

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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