Page last updated: 2024-12-06

guanadrel

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Guanadrel is a non-selective sympatholytic agent that acts by inhibiting the release of norepinephrine from sympathetic nerve endings. It has been used in the treatment of hypertension, but its use has declined due to the availability of more effective and safer antihypertensive drugs. The synthesis of guanadrel involves a multi-step process, starting with the reaction of 2-amino-5-chlorobenzophenone with N,N-dimethylformamide dimethylacetal to give the corresponding Schiff base. This Schiff base is then reacted with lithium aluminum hydride to give the desired product. Guanadrel is a potent inhibitor of norepinephrine release, and it has been shown to be effective in lowering blood pressure in patients with hypertension. However, it has a number of side effects, including drowsiness, dizziness, and dry mouth. These side effects, coupled with the availability of safer and more effective antihypertensive drugs, have led to a decline in the use of guanadrel. Research on guanadrel is ongoing, and there is interest in exploring its potential use in the treatment of other conditions, such as migraine headaches and diabetic neuropathy.'

guanadrel: RN given refers to parent cpd; structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

guanadrel : A spiroketal resulting from the formal condensation of the keto group of cyclohexanone with the hydroxy groups of 1-(2,3-dihydroxypropyl)guanidine. A postganglionic adrenergic blocking agent formerly used (generally as the sulfate salt) for the management of hypertension, it has been largely superseded by other drugs less likely to cause orthostatic hypotension (dizzy spells on standing up or stretching). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID38521
CHEMBL ID1037
CHEBI ID5555
SCHEMBL ID180963
SCHEMBL ID23858317
MeSH IDM0046181

Synonyms (51)

Synonym
CHEMBL1037
BSPBIO_000814
PRESTWICK3_000767
BPBIO1_000896
NCGC00179419-01
PRESTWICK2_000767
AB00513917
guanadrel
40580-59-4
C07035
DB00226
hylorel (tn)
guanadrelum [inn-latin]
guanadrel [inn]
(1,4-dioxaspiro(4.5)dec-2-ylmethyl)guanidine
PRESTWICK0_000767
SPBIO_002753
PRESTWICK1_000767
guanadrelum
1-(1,4-dioxaspiro[4.5]dec-2-ylmethyl)guanidine
CHEBI:5555 ,
2-(1,4-dioxaspiro[4.5]decan-3-ylmethyl)guanidine
L001259
D08029
guanadrel (inn)
FT-0669066
765c9332t4 ,
unii-765c9332t4
guanadrel [vandf]
guanidine (1,4-dioxaspiro(4.5)dec-2-ylmethyl)-
guanadrel [who-dd]
guanadrel [mi]
gtpl7193
1-{1,4-dioxaspiro[4.5]decan-2-ylmethyl}guanidine
SCHEMBL180963
DTXSID2048533
AB00513917_02
AKOS026777091
2-{1,4-dioxaspiro[4.5]decan-2-ylmethyl}guanidine
n-(1,4-dioxaspiro[4.5]dec-2-ylmethyl)guanidine
Q5613557
NCGC00179419-05
EX-A4513
MS-23168
2-((1,4-dioxaspiro[4.5]decan-2-yl)methyl)guanidine
n''-({1,4-dioxaspiro[4.5]decan-2-yl}methyl)guanidine
EN300-37158524
SCHEMBL23858317
HY-W376701
CS-0487434
n-({1,4-dioxaspiro[4.5]decan-2-yl}methyl)guanidine

Research Excerpts

Overview

Guanadrel was found to be an effective antihypertensive agent for all levels of hypertension. Guanadrel sulphate is an orally active peripheral sympathetic inhibitor (adrenergic neuron-blocking drug)

ExcerptReferenceRelevance
"Guanadrel was found to be an effective antihypertensive agent for all levels of hypertension."( Guanadrel. A new antihypertensive drug.
Dunlap, JL; Dunn, MI, 1981
)
2.43
"Guanadrel sulphate is an orally active peripheral sympathetic inhibitor (adrenergic neuron-blocking drug). "( Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension.
Brogden, RN; Finnerty, FA, 1985
)
3.15

Effects

ExcerptReferenceRelevance
"Guanadrel has a rapid onset of action and a half-life of about 10 hours, thus dose titration can be achieved more rapidly than with guanethidine, and twice daily administration is appropriate."( Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension.
Brogden, RN; Finnerty, FA, 1985
)
2.43
"Guanadrel has a rapid onset of action and a half-life of about 10 hours, thus dose titration can be achieved more rapidly than with guanethidine, and twice daily administration is appropriate."( Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension.
Brogden, RN; Finnerty, FA, 1985
)
2.43

Treatment

ExcerptReferenceRelevance
"Guanadrel-treated patients experienced less frequent and less severe drowsiness than methyldopa-treated patients."( Guanadrel sulfate compared with methyldopa for mild and moderate hypertension.
Nugent, CA; Palmer, JD; Ursprung, JJ,
)
2.3

Toxicity

ExcerptReferenceRelevance
" The achievement of normotensive blood pressure levels was accompanied by a decrease in the number of adverse effects reported."( Safety and efficacy of a three-drug regimen for the treatment of hypertension: hydrochlorothiazide, propranolol, and guanadrel.
Gore, RD, 1983
)
0.48
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32

Dosage Studied

The disposition of guanadrel is significantly altered in the presence of renal insufficiency and dosage adjustments may be necessary, especially in patients with ClCr less than 50 ml/min. The drug has a short onset of action and a short offset of action, which prevents many of the side effects.

ExcerptRelevanceReference
" Thus, the disposition of guanadrel is significantly altered in the presence of renal insufficiency and dosage adjustments may be necessary, especially in patients with ClCr less than 50 ml/min."( Disposition of guanadrel in subjects with normal and impaired renal function.
Abraham, PA; Andreadis, NA; Antal, EJ; Halstenson, CE; Matzke, GR; Opsahl, JA; Schwenk, MH, 1989
)
0.93
"To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine, in plasma and urine was required."( Gas chromatographic determination of guanadrel in plasma and urine.
Kaiser, DG; Shah, JA; Vangiessen, GJ; Weber, DJ, 1988
)
0.75
" Dosage varied from 5 to 30 mg/d with a mean of 16 mg/d."( Efficacy and safety of guanadrel in elderly hypertensive patients.
Dunn, MI; Owens, SD, 1988
)
0.59
"The efficacy and safety of low-dose guanadrel sulfate were evaluated in 20 patients with essential hypertension based on seated diastolic blood pressures (SDBP) ranging from 95 to 115 mm Hg despite a trial dosage of hydrochlorothiazide 50 mg/d for up to five weeks."( A dose-titration trial of guanadrel as step-two therapy in essential hypertension.
Ferguson, RK; Koplin, JR; Latini, V; Oren, A; Riley, LJ; Rotmensch, HH; Vlasses, PH,
)
0.71
" Since guanadrel has a short onset of action and a short offset of action, which prevents many of the side effects of guanathidine, the dosage could be adjusted rapidly and safely."( Guanadrel. A new antihypertensive drug.
Dunlap, JL; Dunn, MI, 1981
)
2.16
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
adrenergic antagonistAn agent that binds to but does not activate adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
guanidinesAny organonitrogen compound containing a carbamimidamido (guanidino) group. Guanidines have the general structure (R(1)R(2)N)(R(3)R(4)N)C=N-R(5) and are related structurally to amidines and ureas.
spiroketalA cyclic ketal in which the ketal carbon is the only common atom of two rings.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Spike glycoproteinSevere acute respiratory syndrome-related coronavirusPotency3.98110.009610.525035.4813AID1479145
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Nitric oxide synthase, brain Rattus norvegicus (Norway rat)Activity0.10000.10000.10000.1000AID146288
Nitric oxide synthase, inducibleHomo sapiens (human)Activity0.10000.10000.10000.1000AID92306
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (31)

Processvia Protein(s)Taxonomy
response to hypoxiaNitric oxide synthase, inducibleHomo sapiens (human)
positive regulation of leukocyte mediated cytotoxicityNitric oxide synthase, inducibleHomo sapiens (human)
innate immune response in mucosaNitric oxide synthase, inducibleHomo sapiens (human)
arginine catabolic processNitric oxide synthase, inducibleHomo sapiens (human)
superoxide metabolic processNitric oxide synthase, inducibleHomo sapiens (human)
nitric oxide biosynthetic processNitric oxide synthase, inducibleHomo sapiens (human)
circadian rhythmNitric oxide synthase, inducibleHomo sapiens (human)
response to bacteriumNitric oxide synthase, inducibleHomo sapiens (human)
negative regulation of gene expressionNitric oxide synthase, inducibleHomo sapiens (human)
peptidyl-cysteine S-nitrosylationNitric oxide synthase, inducibleHomo sapiens (human)
prostaglandin secretionNitric oxide synthase, inducibleHomo sapiens (human)
positive regulation of interleukin-6 productionNitric oxide synthase, inducibleHomo sapiens (human)
positive regulation of interleukin-8 productionNitric oxide synthase, inducibleHomo sapiens (human)
regulation of cell population proliferationNitric oxide synthase, inducibleHomo sapiens (human)
negative regulation of protein catabolic processNitric oxide synthase, inducibleHomo sapiens (human)
defense response to bacteriumNitric oxide synthase, inducibleHomo sapiens (human)
regulation of cellular respirationNitric oxide synthase, inducibleHomo sapiens (human)
cell redox homeostasisNitric oxide synthase, inducibleHomo sapiens (human)
regulation of insulin secretionNitric oxide synthase, inducibleHomo sapiens (human)
defense response to Gram-negative bacteriumNitric oxide synthase, inducibleHomo sapiens (human)
positive regulation of killing of cells of another organismNitric oxide synthase, inducibleHomo sapiens (human)
cellular response to lipopolysaccharideNitric oxide synthase, inducibleHomo sapiens (human)
cellular response to type II interferonNitric oxide synthase, inducibleHomo sapiens (human)
cellular response to xenobiotic stimulusNitric oxide synthase, inducibleHomo sapiens (human)
regulation of cytokine production involved in inflammatory responseNitric oxide synthase, inducibleHomo sapiens (human)
negative regulation of blood pressureNitric oxide synthase, inducibleHomo sapiens (human)
response to hormoneNitric oxide synthase, inducibleHomo sapiens (human)
nitric oxide mediated signal transductionNitric oxide synthase, inducibleHomo sapiens (human)
response to lipopolysaccharideNitric oxide synthase, inducibleHomo sapiens (human)
inflammatory responseNitric oxide synthase, inducibleHomo sapiens (human)
positive regulation of guanylate cyclase activityNitric oxide synthase, inducibleHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (11)

Processvia Protein(s)Taxonomy
nitric-oxide synthase activityNitric oxide synthase, inducibleHomo sapiens (human)
protein bindingNitric oxide synthase, inducibleHomo sapiens (human)
calmodulin bindingNitric oxide synthase, inducibleHomo sapiens (human)
FMN bindingNitric oxide synthase, inducibleHomo sapiens (human)
heme bindingNitric oxide synthase, inducibleHomo sapiens (human)
tetrahydrobiopterin bindingNitric oxide synthase, inducibleHomo sapiens (human)
arginine bindingNitric oxide synthase, inducibleHomo sapiens (human)
protein homodimerization activityNitric oxide synthase, inducibleHomo sapiens (human)
metal ion bindingNitric oxide synthase, inducibleHomo sapiens (human)
flavin adenine dinucleotide bindingNitric oxide synthase, inducibleHomo sapiens (human)
NADP bindingNitric oxide synthase, inducibleHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
nucleusNitric oxide synthase, inducibleHomo sapiens (human)
nucleoplasmNitric oxide synthase, inducibleHomo sapiens (human)
cytoplasmNitric oxide synthase, inducibleHomo sapiens (human)
peroxisomeNitric oxide synthase, inducibleHomo sapiens (human)
peroxisomal matrixNitric oxide synthase, inducibleHomo sapiens (human)
cytosolNitric oxide synthase, inducibleHomo sapiens (human)
cortical cytoskeletonNitric oxide synthase, inducibleHomo sapiens (human)
perinuclear region of cytoplasmNitric oxide synthase, inducibleHomo sapiens (human)
plasma membraneNitric oxide synthase, inducibleHomo sapiens (human)
nucleusNitric oxide synthase, inducibleHomo sapiens (human)
cytosolNitric oxide synthase, inducibleHomo sapiens (human)
virion membraneSpike glycoproteinSevere acute respiratory syndrome-related coronavirus
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID92306NO releasing ability of compound measured through formation of nitrite using iNOS (nitric oxide synthases)2001Bioorganic & medicinal chemistry letters, Sep-03, Volume: 11, Issue:17
N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID146288NO releasing ability of compound measured through formation of nitrite using nNOS (nitric oxide synthases)2001Bioorganic & medicinal chemistry letters, Sep-03, Volume: 11, Issue:17
N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (27)

TimeframeStudies, This Drug (%)All Drugs %
pre-199017 (62.96)18.7374
1990's7 (25.93)18.2507
2000's2 (7.41)29.6817
2010's1 (3.70)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 36.26

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index36.26 (24.57)
Research Supply Index3.66 (2.92)
Research Growth Index4.08 (4.65)
Search Engine Demand Index48.45 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (36.26)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials8 (26.67%)5.53%
Reviews2 (6.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other20 (66.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]