Identification

Name
Rivanicline
Accession Number
DB05855
Type
Small Molecule
Groups
Investigational
Description

Rivanicline (TC-2403, RJR-2403, (E)-metanicotine) is a drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It is subtype-selective, binding primarily to the α4β2 subtype. It has nootropic effects and was originally developed as a potential treatment for Alzheimer's disease, but a second action that was subsequently found was that it inhibits the production of Interleukin-8 and thus produces an antiinflammatory effect, and so it has also been developed as a potential treatment for ulcerative colitis. Rivanicline also has stimulant and analgesic actions which are thought to be mediated through stimulation of noradrenaline release, and so it could potentially also have other applications.

Structure
Thumb
Synonyms
  • (3E)-N-methyl-4-(pyridin-3-yl)but-3-en-1-amine
  • (E)-metanicotine
  • (E)-N-Methyl-4-(3-pyridinyl)-3-butene-1-amine
  • N-methyl-4-(3-pyridinyl)-(3E)-3-buten-1-amine
  • trans-metanicotine
External IDs
RJR-2403 / TC-2403
Categories
UNII
6H35LF645A
CAS number
15585-43-0
Weight
Average: 162.2316
Monoisotopic: 162.115698458
Chemical Formula
C10H14N2
InChI Key
JUOSGGQXEBBCJB-GORDUTHDSA-N
InChI
InChI=1S/C10H14N2/c1-11-7-3-2-5-10-6-4-8-12-9-10/h2,4-6,8-9,11H,3,7H2,1H3/b5-2+
IUPAC Name
methyl[(3E)-4-(pyridin-3-yl)but-3-en-1-yl]amine
SMILES
CNCC\C=C\C1=CN=CC=C1

Pharmacology

Indication

Investigated for use/treatment in ulcerative colitis.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Rivanicline is a (E)-metanicotine hemigalactarate. It effectively inhibits TNF- and LPS-induced IL-8 production in different cell types.

TargetActionsOrganism
UNeuronal acetylcholine receptor subunit beta-2Not AvailableHuman
UInterleukin-8
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
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Spoettl T, Paetzel C, Herfarth H, Bencherif M, Schoelmerich J, Greinwald R, Gatto GJ, Rogler G: (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. Int J Colorectal Dis. 2007 Mar;22(3):303-12. Epub 2006 May 20. [PubMed:16715250]
  2. Jang J, Sin KS, Park H: Synthesis of (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines. Arch Pharm Res. 2001 Dec;24(6):503-7. [PubMed:11794523]
  3. Sapronov NS, Fedotova YO, Kuznetsova NN: Antiamnestic effect of alpha7-nicotinic receptor agonist RJR-2403 in middle-aged ovariectomized rats with Alzheimer type dementia. Bull Exp Biol Med. 2006 Dec;142(6):700-2. [PubMed:17603674]
  4. Li X, Eisenach JC: Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology. 2002 Jun;96(6):1450-6. [PubMed:12170059]
External Links
PubChem Compound
5310967
PubChem Substance
175427044
ChemSpider
4470511
BindingDB
50061561
ChEMBL
CHEMBL132966
Wikipedia
Rivanicline

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
Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.74 mg/mLALOGPS
logP1.32ALOGPS
logP1.21ChemAxon
logS-1.5ALOGPS
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area24.92 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity52.22 m3·mol-1ChemAxon
Polarizability19.24 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9951
Blood Brain Barrier+0.9705
Caco-2 permeable+0.7877
P-glycoprotein substrateSubstrate0.6532
P-glycoprotein inhibitor INon-inhibitor0.9388
P-glycoprotein inhibitor IINon-inhibitor0.9564
Renal organic cation transporterInhibitor0.5555
CYP450 2C9 substrateNon-substrate0.7962
CYP450 2D6 substrateSubstrate0.7056
CYP450 3A4 substrateNon-substrate0.7158
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.8863
CYP450 2D6 inhibitorNon-inhibitor0.8652
CYP450 2C19 inhibitorNon-inhibitor0.8969
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9327
Ames testNon AMES toxic0.7565
CarcinogenicityNon-carcinogens0.9354
BiodegradationNot ready biodegradable0.8191
Rat acute toxicity1.8142 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6043
hERG inhibition (predictor II)Non-inhibitor0.8207
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 pyridines and derivatives. These are compounds containing a pyridine ring, which is a six-member aromatic heterocycle which consists of one nitrogen atom and five carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Not Available
Direct Parent
Pyridines and derivatives
Alternative Parents
Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Pyridine / Heteroaromatic compound / Azacycle / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 permeabl...
Gene Name
CHRNB2
Uniprot ID
P17787
Uniprot Name
Neuronal acetylcholine receptor subunit beta-2
Molecular Weight
57018.575 Da
References
  1. Li X, Eisenach JC: Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology. 2002 Jun;96(6):1450-6. [PubMed:12170059]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Interleukin-8 receptor binding
Specific Function
IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response t...
Gene Name
CXCL8
Uniprot ID
P10145
Uniprot Name
Interleukin-8
Molecular Weight
11097.98 Da
References
  1. Spoettl T, Paetzel C, Herfarth H, Bencherif M, Schoelmerich J, Greinwald R, Gatto GJ, Rogler G: (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. Int J Colorectal Dis. 2007 Mar;22(3):303-12. Epub 2006 May 20. [PubMed:16715250]

Drug created on November 18, 2007 11:28 / Updated on December 01, 2017 15:37