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Identification
NameGuanadrel
Accession NumberDB00226  (APRD01006)
TypeSmall Molecule
GroupsApproved
Description

Guanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrine pump or transporter.

Structure
Thumb
Synonyms
Guanadrel
Guanadrelum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AnarelCutter
HylorelPennwalt
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Guanadrel sulfate
22195-34-2
Thumb
  • InChI Key: RTEVGQJRTFFMLL-UHFFFAOYSA-N
  • Monoisotopic Mass: 524.262833446
  • Average Mass: 524.63
DBSALT000889
Categories
UNII765C9332T4
CAS number40580-59-4
WeightAverage: 213.2768
Monoisotopic: 213.147726867
Chemical FormulaC10H19N3O2
InChI KeyInChIKey=HPBNRIOWIXYZFK-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-{1,4-dioxaspiro[4.5]decan-2-ylmethyl}guanidine
SMILES
NC(N)=NCC1COC2(CCCCC2)O1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1,3-dioxolanes. These are organic compounds containing 1,3-dioxolane, an aliphatic five-member ring with two oxygen atoms in ring positions 1 and 3.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDioxolanes
Sub Class1,3-dioxolanes
Direct Parent1,3-dioxolanes
Alternative Parents
Substituents
  • Meta-dioxolane
  • Guanidine
  • Oxacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed to treat and control hypertension.
PharmacodynamicsHigh blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may 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. Guanadrel works by controlling nerve impulses along certain nerve pathways. As a result, it relaxes the blood vessels so that blood passes through them more easily. This helps to lower blood pressure.
Mechanism of actionGuanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrine pump or transporter. Guanadrel slowly displaces norepinephrine from its storage in nerve endings and thereby blocks the release of norepinephrine normally produced by nerve stimulation. The reduction in neurotransmitter release in response to sympathetic nerve stimulation, as a result of catecholamine depletion, leads to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position.
Related Articles
AbsorptionRapidly and readily absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingLow, approximately 20%
Metabolism

Primarily hepatic

Route of eliminationNot Available
Half life10 hours
ClearanceNot Available
ToxicitySide effects include dizziness, drowsiness, headache, constipation, diarrhea, gas pains, loss of appetite, fatigue, and nasal congestion.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8727
Blood Brain Barrier+0.5276
Caco-2 permeable-0.5409
P-glycoprotein substrateNon-substrate0.6176
P-glycoprotein inhibitor INon-inhibitor0.9348
P-glycoprotein inhibitor IINon-inhibitor0.8788
Renal organic cation transporterNon-inhibitor0.5077
CYP450 2C9 substrateNon-substrate0.8797
CYP450 2D6 substrateNon-substrate0.6273
CYP450 3A4 substrateNon-substrate0.7651
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9529
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9413
Ames testNon AMES toxic0.584
CarcinogenicityNon-carcinogens0.9459
BiodegradationNot ready biodegradable0.9371
Rat acute toxicity2.4799 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8914
hERG inhibition (predictor II)Non-inhibitor0.8892
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
  • Pharmaceutical Utilization Management Program VA Inc.
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point213.5-215U.S. Patent 3,547,951.
logP0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.93 mg/mLALOGPS
logP0.03ALOGPS
logP0.62ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)19.85ChemAxon
pKa (Strongest Basic)12.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area82.86 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity56.54 m3·mol-1ChemAxon
Polarizability23.23 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,547,951.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
partial agonist
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Malinow SH: Comparison of guanadrel and guanethidine efficacy and side effects. Clin Ther. 1983;5(3):284-9. [PubMed:6850722 ]
  4. Finnerty FA Jr, Brogden RN: Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs. 1985 Jul;30(1):22-31. [PubMed:3896742 ]
  5. Palmer JD, Nugent CA: Guanadrel sulfate: a postganglionic sympathetic inhibitor for the treatment of mild to moderate hypertension. Pharmacotherapy. 1983 Jul-Aug;3(4):220-9. [PubMed:6351026 ]
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Drug created on June 13, 2005 07:24 / Updated on May 01, 2016 15:32