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 oral dose (poor and highly variable)
Ismelin is converted by the liver to three metabolites, which are excreted in the urine.
Renal cl=56 ml/min
...30 MIN AFTER IP ADMIN OF [(14)C]-GUANETHIDINE, ANTIHYPERTENSIVE AGENT, TO MICE, MOST OF [(14)C] WAS DISTRIBUTED IN LIVER, GI TRACT, SPLEEN, KIDNEYS, URINARY BLADDER, SALIVARY GLANDS, & BROWN FAT. IN RAT, LEVELS...IN PLASMA WERE LOWER THAN IN TISSUES...1-2 HR AFTER IP ADMIN.
HUMAN SUBJECTS RECEIVING GUANETHIDINE, HAD EXCRETED 24% OF [(14)C] IN URINE 24 HR AFTER ORAL DOSE, & 52% AFTER IV DOSE. EXCRETION OF (14)C CONTINUED, & ABOUT HALF AMT EXCRETED IN 24 HR WAS PRESENT IN URINE AFTER FURTHER 48 HR. IN 72 HR ABOUT 23% WAS EXCRETED IN FECES AFTER ORAL DOSE & 3% AFTER IV DOSE.
MUCH OF IV DOSE OF [(3)H]GUANETHIDINE WAS EXCRETED UNCHANGED IN URINE OF HUMAN HYPERTENSIVE SUBJECTS; MORE SLOWLY FROM THOSE SUFFERING ADDITIONALLY FROM RENAL FAILURE.
...PENETRATES CNS VERY POORLY AFTER SYSTEMIC ADMIN. ... GUANETHIDINE IS TAKEN UP BY & STORED IN ADRENERGIC NERVES, & THIS ACCUMULATION IS ESSENTIAL FOR ITS ACTION.
For more Absorption, Distribution and Excretion (Complete) data for GUANETHIDINE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Guanethidine is converted by the liver to three metabolites, which are excreted in the urine. The metabolites are pharmacologically less active than the parent compound.
METABOLISM APPEARS TO BE BY HEPATIC MICROSOMAL ENZYMES, & PERCENTAGE METABOLIZED IS CONSIDERABLY HIGHER AFTER ORAL THAN AFTER PARENTERAL ADMIN.
...TERTIARY NITROGEN OF PERHYDROAZOCINE RING UNDERGOES N-OXIDATION TO SIGNIFICANT EXTENT IN MAN.
HYPOTENSIVE PT ON GUANETHIDINE ELIMINATED VIA KIDNEYS UNCHANGED, ALSO GUANETHIDINE N-OXIDE, & 2-(6-CARBOXYHEXYLAMINO)-ETHYLGUANIDINE.

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Biological Half-Life
1.5 days
...GUANETHIDINE...IS BOUND TO PLASMA PROTEINS & TISSUES, CAUSING PROLONGED T/2 OF ABOUT 30 HR.

Interactions
MONOAMINE OXIDASE INHIBITORS HAVE BEEN REPORTED TO ANTAGONIZE ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE.
TOPICALLY ADMIN GUANETHIDINE ENHANCES RESPONSE OF EYE TO TOPICALLY ADMIN PHENYLEPHRINE, RESULTING IN INCR MYDRIASIS.
THIAZIDES ENHANCE ANTIHYPERTENSIVE ACTION OF GUANETHIDINE, ALLOWING DOSE OF GUANETHIDINE TO BE REDUCED & DECR INCIDENCE OF ADVERSE REACTIONS...
ANTIHYPERTENSIVE ACTION OF GUANETHIDINE MAY BE BLOCKED BY DEXTROAMPHETAMINE & RELATED COMPD; THEREFORE, CONCURRENT USE OF THESE DRUGS SHOULD BE AVOIDED.
For more Interactions (Complete) data for GUANETHIDINE (10 total), please visit the HSDB record 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 member of the class of guanidines in which one of the hydrogens of the amino group has been replaced by a 2-azocan-1-ylethyl group. It has a role as an antihypertensive agent, an adrenergic antagonist and a sympatholytic agent. It is a member of guanidines and a member of azocanes. It is functionally related to a guanidine. It derives from a hydride of an azocane.
An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.

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Drug Indication
For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.

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Mechanism of Action
Guanethidine acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine (NE), rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters to be concentrated within the transmitter vesicles in place of NE, leading to gradual depletion of NE stores in the nerve endings. Guanethidine at the nerve terminal blocks the release of noradrenaline in response to an action potential. In contrast to ganglionic blocking agents, Guanethidine suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, Guanethidine lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.
GUANETHIDINE MAY BE CONSIDERED REPRESENTATIVE OF DRUGS THAT DEPRESS FUNCTION OF POSTGANGLIONIC ADRENERGIC NERVES.
RAPID IV INJECTION...PRODUCES...INITIAL RAPID FALL IN BLOOD PRESSURE ASSOC WITH INCR CARDIAC OUTPUT & DECR PERIPHERAL RESISTANCE; LATTER IS PROBABLY DUE TO TRANSIENT DIRECT ACTION OF DRUG ON RESISTANCE VESSELS. FALL IN BLOOD PRESSURE IS FOLLOWED BY HYPERTENSION...
MAJOR EFFECT...INHIBITION OF RESPONSES TO SYMPATHETIC ADRENERGIC NERVE ACTIVATION & TO INDIRECT-ACTING SYMPATHOMIMETIC AMINES. SINCE GUANETHIDINE ALSO SENSITIZES EFFECTOR CELLS TO CATECHOLAMINES, EFFECTIVE BLOCK MUST MEAN THAT AMT OF MEDIATOR RELEASED IS DRASTICALLY REDUCED. ...HAS CONSIDERABLE LOCAL ANESTHETIC ACTIVITY...
GUANETHIDINE APPARENTLY ACCUMULATES IN & DISPLACES NOREPINEPHRINE FROM INTRANEURONAL STORAGE GRANULES, & IS ITSELF RELEASED BY NERVE STIMULATION. THUS IT FITS DEFINITION OF "FALSE TRANSMITTER" BUT THIS MECHANISM APPEARS NOT TO BE RESPONSIBLE FOR ITS EFFECTS.
For more Mechanism of Action (Complete) data for GUANETHIDINE (7 total), please visit the HSDB record page.

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Therapeutic Uses
Adrenergic Agents; Antihypertensive Agents; Sympatholytics
ONLY MAJOR USE OF GUANETHIDINE IS IN TREATMENT OF HYPERTENSION... IT ALSO EFFECTIVELY CONTROLS PRESSOR EPISODES ASSOC WITH HYPERREFLEXIA OF HIGH SPINAL CORD LESIONS. LOCAL APPLICATION OF GUANETHIDINE HAS RECEIVED LIMITED TRIAL IN TREATMENT OF GLAUCOMA...& TO PRODUCE PARTIAL HORNER'S SYNDROME IN...ABNORMAL EYELID RETRACTION.
GUANETHIDINE...MAY BE USEFUL ADJUNCTS TO ANTITHYROID AGENTS IN HYPERTHYROIDISM & THYROTOXIC CRISIS.
GUANETHIDINE...HAS BEEN USED...IN EYEDROPS FOR REDUCING INTRAOCULAR PRESSURE IN GLAUCOMA & FOR REDUCING LID RETRACTION IN THYROID DISEASE.
For more Therapeutic Uses (Complete) data for GUANETHIDINE (6 total), please visit the HSDB record page.

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Drug Warnings
GUANETHIDINE INHIBITS CARDIOVASCULAR REFLEXES...INCR GASTROINTESTINAL MOTILITY... SALT & WATER RETENTION...CAN PROBABLY BE ACCOUNTED FOR BY HEMODYNAMIC EFFECTS...
SENSITIZATION BY GUANETHIDINE TO SOME SYMPATHOMIMETICS FOUND IN "COLD REMEDIES" CAN RESULT IN HYPERTENSIVE CRISES.

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Pharmacodynamics
High blood pressure can cause the heart and arteries to not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanethidine works by decreasing the heart rate and relaxing the blood vessels so that blood can flow more easily through the body, thereby reducing these risks. It is a postganglionic sympathetic nerve terminal blocker that prevents the release of norepinephrine from nerve terminals.

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.)