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Identification
NameRivanicline
Accession NumberDB05855
TypeSmall Molecule
GroupsInvestigational
DescriptionRivanicline (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 Identifiers
  • RJR-2403
  • TC-2403
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII6H35LF645A
CAS number15585-43-0
WeightAverage: 162.2316
Monoisotopic: 162.115698458
Chemical FormulaC10H14N2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassNot Available
Direct ParentPyridines and derivatives
Alternative Parents
Substituents
  • Pyridine
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in ulcerative colitis.
PharmacodynamicsNot Available
Mechanism of actionRivanicline is a (E)-metanicotine hemigalactarate. It effectively inhibits TNF- and LPS-induced IL-8 production in different cell types.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
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
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 permeable to sodiun ions.
Gene Name:
CHRNB2
Uniprot ID:
P17787
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 to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to rece...
Gene Name:
CXCL8
Uniprot ID:
P10145
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 ]
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Drug created on November 18, 2007 11:28 / Updated on August 17, 2016 12:24