Guanadrel targets the sympathetic nervous system, specifically acting as a postganglionic adrenergic inhibitor. It inhibits the release of norepinephrine from adrenergic nerve terminals, thereby reducing sympathetic tone. This mechanism leads to vasodilation and a decrease in peripheral vascular resistance, which contributes to its antihypertensive effects. It is classified as an antihypertensive agent and a guanidine derivative.

Specific in vitro activity data for Guanadrel are not detailed in the available sources. As an adrenergic inhibitor, its activity would typically be characterized by its ability to inhibit norepinephrine release in isolated tissue preparations or cell-based assays. However, specific IC50 values or detailed pharmacological data are not provided.

Guanadrine has low nervous system toxicity in rats and dogs (15–400 mg/kg daily, 6-52 weeks; oral gavage) [1].
In vivo, Guanadrel is used clinically as an antihypertensive agent. It has been shown to be effective in reducing blood pressure in patients with hypertension. Its oral activity makes it suitable for chronic administration. The compound's efficacy in lowering blood pressure has been established through clinical use, though specific clinical trial data are not provided in the available sources.

A cell-free assay for Guanadrel is not applicable as it is not an enzyme inhibitor with a well-defined target. Its mechanism of action involves the inhibition of neurotransmitter release, which is assessed in functional tissue or cell-based assays rather than cell-free systems.

Cellular assays for Guanadrel would typically involve measuring its effects on neurotransmitter release in cultured neurons or chromaffin cells. Cells are treated with the compound, and the release of norepinephrine or other catecholamines is measured. Guanadrel would be expected to inhibit stimulated neurotransmitter release. Specific protocols are not detailed in the available sources.

Animal/Disease Models: Rats, dogs [1]
Doses: 15-400 mg/kg
Route of Administration: po (oral gavage); daily; 6-52 weeks
Experimental Results: The weight of the prostate and adrenal glands in rats increased slightly, while the weight of the kidneys diminished. Dogs' weight gain diminished in a dose-dependent manner, but liver function was normal.
In vivo animal experiments for Guanadrel are not described in the available sources. As a clinically used antihypertensive drug, its efficacy and safety have been established in human studies. Preclinical studies in animal models of hypertension likely contributed to its development, but specific protocols and data are not provided.

Absorption, Distribution and Excretion
Absorbed rapidly and readily from the gastrointestinal tract. Metabolism/Metabolites: Primarily metabolized in the liver. Biological Half-Life: 10 hours.
Guanadrel is an orally active compound. Specific pharmacokinetic parameters, such as half-life, bioavailability, and metabolism, are not provided in the available sources. As an antihypertensive agent, it is designed for chronic oral administration. The compound is typically administered as the sulfate salt.

Low protein binding, approximately 20%
Toxicity data for Guanadrel are not detailed in the available sources. As a clinically used drug, its safety profile is known, but specific toxicological information is not provided in the references cited. Common adverse effects of adrenergic inhibitors may include orthostatic hypotension, dizziness, and fatigue.

[1]. Guanadrel sulfate: a postganglionic sympathetic inhibitor for the treatment of mild to moderate hypertension. Pharmacotherapy. 1983 Jul-Aug;3(4):220-9. doi: 10.1002/j.1875-9114.1983.tb03257.x.

Guanadrel is a spiroacetal formed by the condensation of the ketone group of cyclohexanone with the hydroxyl group of 1-(2,3-dihydroxypropyl)guanidine. It is a postganglionic adrenergic blocker formerly used to treat hypertension (usually in sulfate form), but has now been superseded by other medications less likely to cause orthostatic hypotension (vertigo upon standing or stretching). Guanadrel has both antihypertensive and adrenergic antagonistic effects. It belongs to the guanidine family and is also a spiroacetal. It is the conjugate base of Guanadrel (1+). Guanadrel is an antihypertensive and postganglionic adrenergic blocker. See also: Guanadrel sulfate (note moved to). Drug Indications For the treatment and control of hypertension. Mechanism of Action Guanadrel is an adrenergic neuron inhibitor that slowly displaces norepinephrine from nerve endings. It blocks the release of norepinephrine caused by sympathetic nerve stimulation, thereby reducing vasoconstriction in small arteries, especially the reflexive increase in sympathetic tone caused by changes in body position.

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Pharmacodynamics
High blood pressure increases the burden on the heart and arteries. If it persists for a long time, the heart and arteries may not function properly. High blood pressure can damage blood vessels in the brain, heart, and kidneys, leading to stroke, heart failure, or kidney failure. High blood pressure also increases the risk of heart attack. If blood pressure is controlled, the chances of these problems occurring are reduced. Guanazore works by controlling nerve impulses on specific neural pathways. Therefore, it can relax blood vessels, making it easier for blood to flow. This helps lower blood pressure.
Guanadrel (CAS: 40580-59-4) is an orally active postganglionic adrenergic inhibitor used as an antihypertensive agent. It works by inhibiting the release of norepinephrine from sympathetic nerve terminals. Its chemical name is N''-({1,4-dioxaspiro[4.5]decan-2-yl}methyl)guanidine. Its molecular formula is C10H19N3O2. It is also known as CL 1388R. It is not commonly used as a first-line antihypertensive in modern practice but remains a research compound.

C10H19N3O2

213.27676

213.148

40580-59-4

22195-34-2 (sulfate[2:1])

38521

Colorless to light yellow ointment

1.39g/cm3

387.9ºC at 760 mmHg

213.5-215ºC

188.4ºC

1.618

1.736

2

3

2

15

245

0

N/C(=N/CC1COC2(CCCCC2)O1)/N

HPBNRIOWIXYZFK-UHFFFAOYSA-N

InChI=1S/C10H19N3O2/c11-9(12)13-6-8-7-14-10(15-8)4-2-1-3-5-10/h8H,1-7H2,(H4,11,12,13)

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

2934.99.9001

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 (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~234.43 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.72 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.72 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (11.72 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.

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