Rivanicline
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Rivanicline
- DrugBank Accession Number
- DB05855
- Background
Rivanicline (TC-2403, RJR-2403, (E)-metanicotine) is a partial agonist at neuronal nicotinic acetylcholine receptors, binding primarily to the α4β2 subtype. It was originally developed as a potential treatment for Alzheimer's disease for its nootropic effects but has also been found to inhibit the production of Interleukin-8. It has subsequently been developed as a potential anti-inflammatory treatment for ulcerative colitis. Rivanicline also has stimulant and analgesic actions which are thought due to increased noradrenaline release.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 162.2316
Monoisotopic: 162.115698458 - Chemical Formula
- C10H14N2
- 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
- Rivanicline
- trans-metanicotine
- External IDs
- RJR-2403
- TC-2403
Pharmacology
- Indication
Investigated for use/treatment in ulcerative colitis.
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- 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.
Target Actions Organism UNeuronal acetylcholine receptor subunit beta-2 Not Available Humans UInterleukin-8 antagonistHumans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound / Pyridine / Secondary aliphatic amine
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 6H35LF645A
- CAS number
- 15585-43-0
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Li X, Eisenach JC: Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology. 2002 Jun;96(6):1450-6. [Article]
- External Links
- PubChem Compound
- 5310967
- PubChem Substance
- 175427044
- ChemSpider
- 4470511
- BindingDB
- 50061561
- ChEMBL
- CHEMBL132966
- ZINC
- ZINC000001543478
- Wikipedia
- Rivanicline
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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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
Property Value Source Water Solubility 4.74 mg/mL ALOGPS logP 1.33 ALOGPS logP 1.21 Chemaxon logS -1.5 ALOGPS pKa (Strongest Basic) 10.47 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 24.92 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 52.22 m3·mol-1 Chemaxon Polarizability 19.24 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9951 Blood Brain Barrier + 0.9705 Caco-2 permeable + 0.7877 P-glycoprotein substrate Substrate 0.6532 P-glycoprotein inhibitor I Non-inhibitor 0.9388 P-glycoprotein inhibitor II Non-inhibitor 0.9564 Renal organic cation transporter Inhibitor 0.5555 CYP450 2C9 substrate Non-substrate 0.7962 CYP450 2D6 substrate Substrate 0.7056 CYP450 3A4 substrate Non-substrate 0.7158 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.8863 CYP450 2D6 inhibitor Non-inhibitor 0.8652 CYP450 2C19 inhibitor Non-inhibitor 0.8969 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9327 Ames test Non AMES toxic 0.7565 Carcinogenicity Non-carcinogens 0.9354 Biodegradation Not ready biodegradable 0.8191 Rat acute toxicity 1.8142 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6043 hERG inhibition (predictor II) Non-inhibitor 0.8207
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0006-9500000000-26be2a9230e472b1a316 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-01q9-0900000000-638e1a594674429ecfc8 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0900000000-c5fa25c602163fb79b85 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0f89-2900000000-60627402177fd3d1bbea Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-1900000000-f4c1a2f7bd71c606b35b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0f6x-9600000000-f73f5a6006e140c9fd7d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0f96-9400000000-4b69ac80470d668e8ac6 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 145.7185359 predictedDarkChem Lite v0.1.0 [M-H]- 135.78816 predictedDeepCCS 1.0 (2019) [M+H]+ 146.4422359 predictedDarkChem Lite v0.1.0 [M+H]+ 139.16011 predictedDeepCCS 1.0 (2019) [M+Na]+ 146.1018359 predictedDarkChem Lite v0.1.0 [M+Na]+ 148.52534 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General 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
- Specific Function
- acetylcholine binding
- Gene Name
- CHRNB2
- Uniprot ID
- P17787
- Uniprot Name
- Neuronal acetylcholine receptor subunit beta-2
- Molecular Weight
- 57018.575 Da
References
- Li X, Eisenach JC: Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology. 2002 Jun;96(6):1450-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also plays an important role in neutrophil activation (PubMed:2145175, PubMed:9623510). Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells (PubMed:1840701, PubMed:1891716). G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways (PubMed:11971003, PubMed:8662698)
- Specific Function
- chemokine activity
- Gene Name
- CXCL8
- Uniprot ID
- P10145
- Uniprot Name
- Interleukin-8
- Molecular Weight
- 11097.98 Da
References
- 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. [Article]
Drug created at November 18, 2007 18:28 / Updated at February 21, 2021 18:51