Identification

Name
Bethanidine
Accession Number
DB00217  (APRD00825)
Type
Small Molecule
Groups
Approved
Description

A guanidinium antihypertensive agent that acts by blocking adrenergic transmission.

Structure
Thumb
Synonyms
  • Betanidina
  • Betanidine
  • Bétanidine
  • Betanidinum
  • Bethanidine
  • N,N'-dimethyl-N''-(phenylmethyl)-guanidine
Product Ingredients
IngredientUNIICASInChI Key
Bethanidine sulfateJ4THI5N7O2114-85-2YTIJUXVIZLYQTB-UHFFFAOYSA-N
International/Other Brands
Esbatal
Categories
UNII
W8S3YM7AUU
CAS number
55-73-2
Weight
Average: 177.2462
Monoisotopic: 177.126597495
Chemical Formula
C10H15N3
InChI Key
NIVZHWNOUVJHKV-UHFFFAOYSA-N
InChI
InChI=1S/C10H15N3/c1-11-10(12-2)13-8-9-6-4-3-5-7-9/h3-7H,8H2,1-2H3,(H2,11,12,13)
IUPAC Name
(E)-3-benzyl-1,2-dimethylguanidine
SMILES
CN\C(NCC1=CC=CC=C1)=N/C

Pharmacology

Indication

For the treatment of hypertension.

Pharmacodynamics

Bethanidine is a guanidinium antihypertensive agent that acts by blocking adrenergic transmission. The precise mode of action is not clear. Although bethanidine may produce adverse effects, they are beneficial in severe hypertension and produce fewer side effects than guanethidine.

Mechanism of action

Bethanidine, a guanidine derivative, is a peripherally acting antiadrenergic agent which primarily acts as an alpha2a adrenergic agonist. Bethanidine effectively decreases blood pressure by suppressing renin secretion or interfering with function of the sympathetic nervous system.

TargetActionsOrganism
AAlpha-2 adrenergic receptors
agonist
Human
AATP-sensitive inward rectifier potassium channel 1
inhibitor
Human
UBeta adrenergic receptor
antagonist
Human
Absorption

Absorbed rapidly in the gastrointestinal tract following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

9 hours (range 7 to 11 hours)

Clearance
Not Available
Toxicity
Not Available
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 AcidBethanidine may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Bethanidine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Bethanidine is combined with 5-methoxy-N,N-dimethyltryptamine.
AbediterolThe risk or severity of hypertension can be increased when Bethanidine is combined with Abediterol.
AcebutololThe therapeutic efficacy of Bethanidine can be decreased when used in combination with Acebutolol.
Food Interactions
Not Available

References

Synthesis Reference

Khashayar Karimian, Keshava Murthy, Darren Hall, "Methods of making ureas and guanidines, including terazosin, prazosin, doxazosin, tiodazosin, trimazosin, quinazosin, and bunazosin (exemplary of 2-substituted quinazoline compounds), and meobentine, and bethanidine and intermediates thereof." U.S. Patent US5686612, issued November, 1990.

US5686612
General References
Not Available
External Links
Human Metabolome Database
HMDB0014362
KEGG Drug
D01603
PubChem Compound
2368
PubChem Substance
46507605
ChemSpider
2278
ChEBI
37937
ChEMBL
CHEMBL1201260
Therapeutic Targets Database
DAP000047
PharmGKB
PA164743235
Wikipedia
Bethanidine
ATC Codes
C02CC01 — Betanidine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Ah robins co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196 °CPhysProp
logP0.49Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.58 mg/mLALOGPS
logP1.41ALOGPS
logP1.27ChemAxon
logS-2ALOGPS
pKa (Strongest Basic)12.41ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area36.42 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity54.5 m3·mol-1ChemAxon
Polarizability20.43 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9713
Blood Brain Barrier+0.85
Caco-2 permeable+0.5072
P-glycoprotein substrateNon-substrate0.5681
P-glycoprotein inhibitor INon-inhibitor0.9217
P-glycoprotein inhibitor IINon-inhibitor0.6727
Renal organic cation transporterInhibitor0.5516
CYP450 2C9 substrateNon-substrate0.7952
CYP450 2D6 substrateNon-substrate0.5
CYP450 3A4 substrateNon-substrate0.7359
CYP450 1A2 substrateNon-inhibitor0.7802
CYP450 2C9 inhibitorNon-inhibitor0.9218
CYP450 2D6 inhibitorInhibitor0.5754
CYP450 2C19 inhibitorNon-inhibitor0.8195
CYP450 3A4 inhibitorNon-inhibitor0.8329
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9069
Ames testNon AMES toxic0.7985
CarcinogenicityNon-carcinogens0.886
BiodegradationNot ready biodegradable0.9161
Rat acute toxicity2.5507 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9126
hERG inhibition (predictor II)Non-inhibitor0.9191
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 benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Guanidines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Organopnictogen compounds / Imines / Hydrocarbon derivatives
Substituents
Monocyclic benzene moiety / Guanidine / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Imine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
guanidines (CHEBI:37937)

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Noshiro T, Miura Y, Kimura S, Meguro Y, Sugawara T, Ohashi H, Takahashi M, Sano N, Watanabe H, Ohzeki T, et al.: Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity in clinical hypertensive states. J Hypertens. 1990 Dec;8(12):1097-104. [PubMed:1962798]
  2. Noshiro T, Miura Y, Kimura S, Meguro Y, Sugawara T, Ohashi H, Takahashi M, Sano N, Watanabe H, Ohzeki T, et al.: Functional relationship between platelet alpha 2-adrenoceptors and sympathetic nerve activity in man. Clin Exp Hypertens A. 1989;11 Suppl 1:287-94. [PubMed:2545383]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Phosphatidylinositol-4,5-bisphosphate binding
Specific Function
In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than...
Gene Name
KCNJ1
Uniprot ID
P48048
Uniprot Name
ATP-sensitive inward rectifier potassium channel 1
Molecular Weight
44794.6 Da
References
  1. Bkaily G, Caille JP, Payet MD, Peyrow M, Sauve R, Renaud JF, Sperelakis N: Bethanidine increases one type of potassium current and relaxes aortic muscle. Can J Physiol Pharmacol. 1988 Jun;66(6):731-6. [PubMed:3167688]
  2. Bkaily G: Bethanidine, nitroprusside and atrial natriuretic factor open a cGMP-sensitive K+ channel in aortic muscle. Prog Clin Biol Res. 1990;327:507-15. [PubMed:2157221]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...

Components:
References
  1. Hart GR, Anderson RJ: Withdrawal syndromes and the cessation of antihypertensive therapy. Arch Intern Med. 1981 Aug;141(9):1125-7. [PubMed:6114720]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Bacaner MB, Benditt DG: Antiarrhythmic, antifibrillatory, and hemodynamic actions of bethanidine sulfate: an orally effective analog of bretylium for suppression of ventricular tachyarrhythmias. Am J Cardiol. 1982 Oct;50(4):728-34. [PubMed:6812406]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 14:49