Details of the Drug

General Information of Drug (ID: DMWX5CO)

Drug Name
Nicotine
Synonyms
Habitrol; Micotine; NCT; NICOTINE AND SALTS; Nicoderm Patch; Nicotina [Italian]; Nicotine Patch; Nicotine [USAN]; Nicotine replacement patch; Nicotine solution; Nictoine patch; Nikotin [German]; Nikotyna [Polish]; Transdermal Nicotine; Nicotine [UN1654] [Poison]; ENT 3,424; Habitrol (TN); Nicorette (TN); Nicotine (USP); Nicotine (compounds related to); Nicotine [BSI:ISO]; L(-)-nicotine; Beta-Pyridyl-alpha-N-methyl pyrrolidine; (-)-Nicotine solution; (2S) 3-(1-Methyl-pyrrolidin-2-yl)-pyridine; (S)-(-)-NICOTINE, 3-[(2S)-1-METHYL-2-PYRROLIDINYL] PYRIDINE; (S)-(-)-Nicotine; (S)-3-(1-methylpyrrolidin-2-yl)pyridine; (S)-3-(N-methylpyrrolidin-2-yl)pyridine; (S)-Nicotine; 3-(2-(N-methylpyrrolidinyl))pyridine; 3-(N-Methylpyrollidino)pyridine; 3-(N-Methylpyrrolidino)pyridine; 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
Indication
Disease Entry ICD 11 Status REF
Lung cancer 2C25.0 Approved [1]
Nicotine dependence 6C4A.2 Approved [2]
Pellagra N.A. Approved [1]
Tobacco dependence 6C4A.2 Clinical trial [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 162.23
Logarithm of the Partition Coefficient (xlogp) 1.2
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Clearance
The clearance of drug is 1.2 L/min in healthy adult smoker []
Elimination
16.7% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 15 - 20 hours [5]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.522 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.95% [5]
Vd
The volume of distribution (Vd) of drug is 2-3 L/kg []
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Bladder transitional cell carcinoma Not Available PIK3CB PIK3C1 OTO8JQJA [7]
Cell death Not Available COL1A1 OTI31178 [7]
Drug tolerance increased Not Available CHAT OTEJWQ45 [7]
Chemical Identifiers
Formula
C10H14N2
IUPAC Name
3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
Canonical SMILES
CN1CCC[C@H]1C2=CN=CC=C2
InChI
InChI=1S/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
InChIKey
SNICXCGAKADSCV-JTQLQIEISA-N
Cross-matching ID
PubChem CID
89594
ChEBI ID
CHEBI:17688
CAS Number
54-11-5
DrugBank ID
DB00184
TTD ID
D0T8GD
VARIDT ID
DR00679
INTEDE ID
DR1148
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Nicotinic acetylcholine receptor (nAChR) TTJSZTB NOUNIPROTAC Antagonist [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [9]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [9]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [9]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [9]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Substrate [14]
Nicotinate dehydrogenase (nicA) DE4AMLP NICA_PSEPK Substrate [15]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Gene/Protein Processing [16]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Gene/Protein Processing [17]
2'-5'-oligoadenylate synthase 1 (OAS1) OT8ZLOCY OAS1_HUMAN Gene/Protein Processing [18]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1) OTNAZVKB 3BHS1_HUMAN Gene/Protein Processing [17]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Gene/Protein Processing [19]
3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7) OTV7VOV3 DHB7_HUMAN Gene/Protein Processing [18]
5'-deoxynucleotidase HDDC2 (HDDC2) OTSO0JP4 HDDC2_HUMAN Gene/Protein Processing [18]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Gene/Protein Processing [20]
Activity-regulated cytoskeleton-associated protein (ARC) OTN2QQPG ARC_HUMAN Gene/Protein Processing [18]
Acylamino-acid-releasing enzyme (APEH) OTX258QE ACPH_HUMAN Gene/Protein Processing [21]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Nicotine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Alpelisib DMEXMYK Moderate Increased metabolism of Nicotine caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [22]
Cenobamate DM8KLU9 Moderate Increased metabolism of Nicotine caused by Cenobamate mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [23]
Fenofibrate DMFKXDY Moderate Decreased metabolism of Nicotine caused by Fenofibrate mediated inhibition of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [24]
Ceritinib DMB920Z Moderate Decreased metabolism of Nicotine caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [24]
Abametapir DM2RX0I Moderate Decreased metabolism of Nicotine caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [25]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Nicotine caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [22]
⏷ Show the Full List of 6 DDI Information of This Drug

References

1 Nicotine FDA Label
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2585).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 BDDCS applied to over 900 drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
8 Atypical antipsychotics as noncompetitive inhibitors of alpha4beta2 and alpha7 neuronal nicotinic receptors. Neuropharmacology. 2009 Aug;57(2):183-91.
9 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
10 Effects of nicotine on cytochrome P450 2A6 and 2E1 activities. Br J Clin Pharmacol. 2010 Feb;69(2):152-9.
11 Liquid chromatography-tandem mass spectrometry method for measurement of nicotine N-glucuronide: a marker for human UGT2B10 inhibition. J Pharm Biomed Anal. 2011 Jul 15;55(5):964-71.
12 CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
13 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
14 Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism. J Pharmacol Exp Ther. 2006 Jan;316(1):295-303.
15 Optimization of a nicotine degrading enzyme for potential use in treatment of nicotine addiction. BMC Biotechnol. 2019 Aug 2;19(1):56.
16 nAChRs-ERK1/2-Egr-1 signaling participates in the developmental toxicity of nicotine by epigenetically down-regulating placental 11beta-HSD2. Toxicol Appl Pharmacol. 2018 Apr 1;344:1-12.
17 Decreased levels of H3K9ac and H3K27ac in the promotor region of ovarian P450 aromatase mediated low estradiol synthesis in female offspring rats induced by prenatal nicotine exposure as well as in human granulosa cells after nicotine treatment. Food Chem Toxicol. 2019 Jun;128:256-266. doi: 10.1016/j.fct.2019.03.055. Epub 2019 Apr 6.
18 Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
19 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
20 Nicotine treatment induces expression of matrix metalloproteinases in human osteoblastic Saos-2 cells. Acta Biochim Biophys Sin (Shanghai). 2006 Dec;38(12):874-82. doi: 10.1111/j.1745-7270.2006.00240.x.
21 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
22 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
23 Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
24 Cerner Multum, Inc. "Australian Product Information.".
25 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.