Absorption, Distribution and Excretion
Following oral administration, guanaril sulfate is rapidly and almost completely absorbed. Peak plasma concentrations are typically reached 1.5–2 hours after oral administration. The hypotensive effect of guanaril sulfate typically begins in 0.5–2 hours, peaks at 4–6 hours, and lasts for 4–14 hours. Approximately 20% of guanaril sulfate is bound to plasma proteins over a wide concentration range. The drug is widely distributed in most body tissues and fluids. It does not cross the blood-brain barrier or reach the eyes. It is currently unknown whether guanaril sulfate is distributed in breast milk or crosses the placenta. In mice, the drug has been shown to cross the placenta at low concentrations. Guanaril sulfate is eliminated from the body via renal and non-renal routes. Drug clearance is impaired in patients with renal insufficiency; in a group of patients with an average creatinine clearance of 13 mL/min, systemic clearance was reduced by 4 to 5 times. Approximately 40–50% of the drug is metabolized in the liver… Guanazine and its metabolites are primarily excreted in the urine. Approximately 85% of the oral dose is excreted in the urine within 24 hours; 40-50% is excreted unchanged in the urine. Metabolites/Metabolites: Approximately 40-50% of the drug is metabolized in the liver to 2,3-dihydroxypropylguanidine and several unidentified metabolites. The antihypertensive activity of the metabolites is unknown. Biological Half-Life: Plasma concentrations of guanazine exhibit a biphasic decline. Significant individual variability exists in the plasma half-life of this drug. In patients with normal renal function, the initial plasma half-life of guanazine is approximately 2 hours (range: 1-4 hours), and the elimination half-life is approximately 10-12 hours (range: 5-45 hours).

Interactions
Tricyclic antidepressants, phenothiazines, and indirect-acting sympathomimetic drugs (such as ephedrine and phenylpropanolamine) may block guanaril from entering adrenergic neurons or reverse its hypotensive effect. Ephedrine has been shown to rapidly reverse the pharmacological effects of guanaril. Guanaril may enhance the pharmacological activity of directly acting sympathomimetic drugs (such as norepinephrine or phenylephrine). Monoamine oxidase inhibitors have been reported to antagonize the hypotensive effect of guanaril; ...guanaril is contraindicated in patients taking monoamine oxidase inhibitors, and these drugs should be discontinued at least one week before starting guanaril. Because guanaril may enhance the pressor and arrhythmogenic effects of vasopressors, vasopressors should be used with caution. Patients taking guanalenafil should exercise extreme caution when discontinuing tricyclic antidepressants, especially abruptly, as this may enhance the clinical effects of guanalenafil (e.g., hypotension). Because many over-the-counter cold, allergy, and asthma medications contain sympathomimetic agents, patients taking guanalenafil should be advised not to use these medications without first consulting a doctor or pharmacist. For more complete data on drug interactions for guanalenafil sulfate (6 types), please visit the HSDB records page.

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Non-human toxicity values
Rats oral LD50: 2220 mg/kg
Rats intravenous LD50: 26 mg/kg
Dogs oral LD50: 225 mg/kg
Dogs intravenous LD50: 45 mg/kg
For more complete data on non-human toxicity values for guanalenafil sulfate (6 types), please visit the HSDB records page.

Guanadrel sulfate is an organic sulfate formed by the reaction of 2 equivalents of Guanadrel with 1 equivalent of sulfuric acid. It is a postganglionic adrenergic blocker, formerly used to treat hypertension, but has been superseded by other drugs less likely to cause orthostatic hypotension (dizziness upon standing or stretching). It has the effects of both adrenergic antagonists and antihypertensive drugs. It contains a Guanadrel (1+) group.
See also: Guanadrel (with active moiety).

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Mechanism of Action
Guinaranarel specifically targets peripheral adrenergic neurons, inhibiting sympathetic nerve function. The drug is actively transported into neurons via the same transporter as norepinephrine reuptake, thus reaching its site of action. In neurons, Guanadrel concentrates within neurosecretory vesicles and replaces norepinephrine. With prolonged administration, Guanadrel acts as a "substitute neurotransmitter" because it is present in storage vesicles, depletes normal neurotransmitters, and can be released by stimuli that normally release norepinephrine. The primary mechanism by which it replaces norepinephrine with an inactive neurotransmitter is likely its blocking effect on neurons. Similar to guanethidine, guanaril sulfate selectively blocks efferent peripheral sympathetic pathways. This drug depletes the norepinephrine reserves at adrenergic nerve endings, and unlike guanethidine, it also depletes norepinephrine in the adrenal medulla; guanaril also prevents the release of norepinephrine from adrenergic nerve endings induced by sympathetic stimulation. Guanaril has been reported to deplete norepinephrine reserves in the gastrointestinal tract to a lesser extent than guanethidine. Long-term use of guanaril can increase the sensitivity of effector cells to catecholamines. Following oral administration of guanaril, depletion of catecholamine reserves leads to a decrease in blood pressure, usually (but not always) accompanied by a decrease in heart rate of 5 to 10 beats per minute. Venous dilation and peripheral blood stasis may result in a slight decrease or no change in cardiac output. Total peripheral resistance usually decreases slightly.

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Therapeutic Use
Antihypertensive Drug
Eleven patients with Graves' disease received guanaril sulfate treatment, and changes in their neuromuscular and cardiovascular manifestations were observed. During the 3-day pretreatment period, no significant changes were observed in pulse rate or muscle strength in these patients; similar changes were not observed in 5 control patients with Graves' disease who received placebo for 6 days. Seven days of guanaril sulfate treatment did not alter thyroid hormone levels or cause adverse reactions. The mean supine resting pulse decreased from 102±6 bpm (mean ± standard error) to 90±3 bpm (P<0.02). Compared with healthy subjects, patients initially showed decreased proximal and distal muscle strength, but this significantly improved after guanaril sulfate treatment. We conclude that guanaril sulfate may be helpful in the symptomatic treatment of patients with thyrotoxicosis.
Because many antihypertensive drugs do not cause orthostatic hypotension, guanaril is not used as a monotherapy for hypertension but is primarily used as an adjunct therapy for patients who do not respond well to two or more other antihypertensive drugs.
Drug Warnings
Patients and clinicians should be aware that guanaril may cause significant orthostatic hypotension and the resulting dizziness, weakness, and syncope. Clinicians should monitor patients' blood pressure in both standing and supine positions, as monitoring supine blood pressure alone may not detect the possibility of orthostatic hypotension. Patients should be advised to avoid sudden or prolonged standing (especially in the morning) or exercise, and to take appropriate action if dizziness or weakness occurs (e.g., lie down or sit down). High temperatures, alcohol consumption, or fever may worsen orthostatic hypotension. Elderly patients should use this medication with caution due to the risk of orthostatic hypotension. Elderly patients may be more sensitive to sympathetic inhibition than younger patients because they often have impaired cardiovascular reflexes and are more prone to hypotension.
Guinaril should be used with caution in patients with bronchial asthma, as catecholamine depletion in these patients may worsen asthma, and sympathomimetic drugs used to treat asthma may interfere with the antihypertensive effect of guanaril. Patients with peptic ulcers should also use this medication with caution, as the relative increase in parasympathetic tone caused by guanaril may worsen the condition. Guanaril should be discontinued 2-3 days before elective surgery to reduce the risk of cardiovascular failure and cardiac arrest during anesthesia. If emergency surgery is required, the anesthesiologist should be informed that the patient is taking this medication, and preoperative anesthesia and anesthetic drugs should be used with caution and at reduced doses. Vasopressors should be used with caution because guanaril may enhance the pressor and arrhythmic effects of vasopressors. Guanaril should be used with caution in patients who may be affected by sodium and water retention; however, this effect can usually be overcome by concurrent use of diuretics. For more complete data on drug warnings for guanaril sulfate (19 in total), please visit the HSDB record page.

C10H21N3O6S

311.35524

311.115

22195-34-2

40580-59-4 (Parent)

68552

White to off-white crystalline powder
Crystals from methanol/ethanol

1.39 g/cm3

387.9ºC at 760 mmHg

235ºC

188.4ºC

1.618

2.164

6

10

4

35

326

0

C1CCC2(CC1)OCC(CNC(=N)N)O2.C1CCC2(CC1)OCC(CNC(=N)N)O2.OS(=O)(=O)O

RTEVGQJRTFFMLL-UHFFFAOYSA-N

InChI=1S/2C10H19N3O2.H2O4S/c2*11-9(12)13-6-8-7-14-10(15-8)4-2-1-3-5-10;1-5(2,3)4/h2*8H,1-7H2,(H4,11,12,13);(H2,1,2,3,4)

2-(1,4-dioxaspiro[4.5]decan-3-ylmethyl)guanidine;sulfuric acid

Guanadrel Sulfate Hyloride Hylorel

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.)