Identification

Name
Guanadrel
Accession Number
DB00226  (APRD01006)
Type
Small Molecule
Groups
Approved
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
Product Ingredients
IngredientUNIICASInChI Key
Guanadrel sulfateMT147RMO9122195-34-2RTEVGQJRTFFMLL-UHFFFAOYSA-N
International/Other Brands
Anarel (Cutter) / Hylorel (Pennwalt)
Categories
UNII
765C9332T4
CAS number
40580-59-4
Weight
Average: 213.2768
Monoisotopic: 213.147726867
Chemical Formula
C10H19N3O2
InChI Key
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

Pharmacology

Indication

Used to treat and control hypertension.

Pharmacodynamics

High 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 action

Guanadrel 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.

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
partial agonist
Human
Absorption

Rapidly and readily absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

Low, approximately 20%

Metabolism

Primarily hepatic

Route of elimination
Not Available
Half life

10 hours

Clearance
Not Available
Toxicity

Side effects include dizziness, drowsiness, headache, constipation, diarrhea, gas pains, loss of appetite, fatigue, and nasal congestion.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidGuanadrel may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
AcebutololGuanadrel may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Guanadrel can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Guanadrel can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Guanadrel can be decreased when used in combination with Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Guanadrel can be decreased when used in combination with Alclofenac.
AlfuzosinAlfuzosin may increase the hypotensive activities of Guanadrel.
AliskirenGuanadrel may increase the hypotensive activities of Aliskiren.
AlminoprofenThe therapeutic efficacy of Guanadrel can be decreased when used in combination with Alminoprofen.
AlprenololGuanadrel may increase the hypotensive activities of Alprenolol.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 3,547,951.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014371
KEGG Drug
D08029
KEGG Compound
C07035
PubChem Compound
38521
PubChem Substance
46506457
ChemSpider
35305
ChEBI
5555
ChEMBL
CHEMBL1037
Therapeutic Targets Database
DAP000059
PharmGKB
PA164745308
Drugs.com
Drugs.com Drug Page
Wikipedia
Guanadrel

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
Packagers
  • Pharmaceutical Utilization Management Program VA Inc.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213.5-215U.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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as ketals. These are acetals derived from ketones by replacement of the oxo group by two hydrocarbyloxy groups R2C(OR)2 ( R not Hydrogen ). This term, once abandoned, has been reinstated as a subclass of acetals.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Ketals
Alternative Parents
1,3-dioxolanes / Guanidines / Oxacyclic compounds / Carboximidamides / Organopnictogen compounds / Imines / Hydrocarbon derivatives
Substituents
Ketal / Meta-dioxolane / Guanidine / Oxacycle / Organoheterocyclic compound / Carboximidamide / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
guanidines, spiroketal (CHEBI:5555)

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
Uniprot Name
Sodium-dependent noradrenaline transporter
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]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 21:12