Identification

Name
Pentolinium
Accession Number
DB01090  (APRD00038)
Type
Small Molecule
Groups
Approved
Description

A nicotinic antagonist that has been used as a ganglionic blocking agent in hypertension. [PubChem]

Structure
Thumb
Synonyms
  • Pentolineum
  • Pentolonium
  • Pentolonum
Product Ingredients
IngredientUNIICASInChI Key
Pentolinium tartrate953357GACY52-62-0HSMKTIKKPMTUQH-WBPXWQEISA-L
International/Other Brands
Ansolysen
Categories
UNII
ULL76WPU5X
CAS number
144-44-5
Weight
Average: 240.428
Monoisotopic: 240.256549034
Chemical Formula
C15H32N2
InChI Key
XSBSKEQEUFOSDD-UHFFFAOYSA-N
InChI
InChI=1S/C15H32N2/c1-16(12-6-7-13-16)10-4-3-5-11-17(2)14-8-9-15-17/h3-15H2,1-2H3/q+2
IUPAC Name
1-methyl-1-[5-(1-methylpyrrolidin-1-ium-1-yl)pentyl]pyrrolidin-1-ium
SMILES
C[N+]1(CCCCC[N+]2(C)CCCC2)CCCC1

Pharmacology

Indication

Used to produce controlled hypotension during surgical procedures and in hypertensive crises.

Pharmacodynamics

Pentolinium acts as a ganglionic blocking agent. Pentolinium inhibits release of adrenaline and noradrenaline from adrenergic nerves. It is used as an antihypertensive, and can be administered orally, intramuscularly, and subcutaneously.

Mechanism of action

Pentolinium binds to the nicotinic (ganglion) acetylcholine receptor. This receptor/channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. Blockage of the receptor leads to smooth muscle relaxation and vasodilaton.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-10
antagonist
Human
ANeuronal acetylcholine receptor subunit alpha-3
antagonist
Human
ANeuronal acetylcholine receptor subunit beta-4
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Oral, mouse: LD50 = 512 mg/kg; Oral, rat: LD50 = 890 mg/kg.

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 AcidPentolinium may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1,10-PhenanthrolineThe therapeutic efficacy of Pentolinium can be decreased when used in combination with 1,10-Phenanthroline.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Pentolinium.
AcebutololPentolinium may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Acemetacin.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Pentolinium.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Acetyl sulfisoxazole is combined with Pentolinium.
Acetylsalicylic acidThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumThe risk or severity of adverse effects can be increased when Pentolinium is combined with Aclidinium.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015222
PubChem Compound
5850
PubChem Substance
46507977
ChemSpider
5641
BindingDB
50084945
ChEBI
347401
ChEMBL
CHEMBL1271
Therapeutic Targets Database
DAP001144
PharmGKB
PA164777033
Wikipedia
Pentolinium
MSDS
Download (61.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213 °C (tartrate salt)Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.16e-05 mg/mLALOGPS
logP-2.3ALOGPS
logP-6.3ChemAxon
logS-7.4ALOGPS
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity99.03 m3·mol-1ChemAxon
Polarizability31.36 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9722
Blood Brain Barrier+0.9922
Caco-2 permeable+0.6627
P-glycoprotein substrateSubstrate0.5993
P-glycoprotein inhibitor INon-inhibitor0.9697
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterInhibitor0.6294
CYP450 2C9 substrateNon-substrate0.8782
CYP450 2D6 substrateNon-substrate0.607
CYP450 3A4 substrateNon-substrate0.5941
CYP450 1A2 substrateNon-inhibitor0.9834
CYP450 2C9 inhibitorNon-inhibitor0.9533
CYP450 2D6 inhibitorNon-inhibitor0.9312
CYP450 2C19 inhibitorNon-inhibitor0.9348
CYP450 3A4 inhibitorNon-inhibitor0.9943
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9857
Ames testNon AMES toxic0.758
CarcinogenicityNon-carcinogens0.8783
BiodegradationReady biodegradable0.7183
Rat acute toxicity2.7632 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7283
hERG inhibition (predictor II)Non-inhibitor0.7476
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-alkylpyrrolidines. These are compounds containing a pyrrolidine moiety that is substituted at the N1-position with an alkyl group. Pyrrolidine is a five-membered saturated aliphatic heterocycle with one nitrogen atom and four carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolidines
Sub Class
N-alkylpyrrolidines
Direct Parent
N-alkylpyrrolidines
Alternative Parents
Tetraalkylammonium salts / Azacyclic compounds / Organopnictogen compounds / Organic salts / Hydrocarbon derivatives / Amines / Organic cations
Substituents
N-alkylpyrrolidine / Tetraalkylammonium salt / Quaternary ammonium salt / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organic salt / Organonitrogen compound / Amine
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
organic cation (CHEBI:347401)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor binding
Specific Function
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an i...
Gene Name
CHRNA10
Uniprot ID
Q9GZZ6
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-10
Molecular Weight
49704.295 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. McKay DB, Burkman AM: Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6. [PubMed:8516349]
  4. Cachelin AB, Rust G: Beta-subunits co-determine the sensitivity of rat neuronal nicotinic receptors to antagonists. Pflugers Arch. 1995 Jan;429(3):449-51. [PubMed:7761270]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA3
Uniprot ID
P32297
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-3
Molecular Weight
57479.54 Da
References
  1. Cachelin AB, Rust G: Beta-subunits co-determine the sensitivity of rat neuronal nicotinic receptors to antagonists. Pflugers Arch. 1995 Jan;429(3):449-51. [PubMed:7761270]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNB4
Uniprot ID
P30926
Uniprot Name
Neuronal acetylcholine receptor subunit beta-4
Molecular Weight
56378.985 Da
References
  1. Cachelin AB, Rust G: Beta-subunits co-determine the sensitivity of rat neuronal nicotinic receptors to antagonists. Pflugers Arch. 1995 Jan;429(3):449-51. [PubMed:7761270]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:35