Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMT3KB4)

• Drug Name: Lobeline Drug Info
• Synonyms: lobeline; Lobelin; Inflatine; Lobeline [INN]; Lobelinum [INN-Latin]; Lobelina [INN-Spanish]; EINECS 202-012-3; BRN 0091533; AC1LEL62; ZINC56446; Ethanone, 2-(6-(2-hydroxy-2-phenylethyl)-1-methyl-2-piperidinyl)-1-phenyl-, (2R-(2alpha,6alpha(S*)))-; LS-88107

Indication

Disease Entry	ICD 11	Status	REF
Substance use disorder	6C4Z	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 101616
  ChEBI ID: CHEBI:48723
  CAS Number: CAS 90-69-7
  TTD Drug ID: DMT3KB4
  VARIDT Drug ID: DR01063

Molecule-Related Drug Atlas

Drug(s) Targeting Synaptic vesicle amine transporter (SLC18A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Deutetrabenazine	DMUPFLI	Huntington disease	8A01.10	Approved	[5]
Reserpine	DM6VM38	Hypertension	BA00-BA04	Approved	[6]
Tetrabenazine	DMYWQ0O	Huntington disease	8A01.10	Approved	[6]
Alseroxylon	DMB47TQ	Hypertension	BA00-BA04	Approved	[7]
Valbenazine Tosylate	DMQSA2V	Tardive dyskinesia	8A02.10	Approved	[5]
Alkavervir	DMB4HFI	High blood pressure	BA00	Approved	[5]
Ingrezza	DMVPLNC	Tardive dyskinesia	8A02.10	Phase 4	[8]
NBI-98854	DMVO1C0	Movement disorder	8A07-8A0Z	Phase 3	[9]
AV 133	DM0EQ9X	Alzheimer disease	8A20	Phase 3	[10]
SOM3355	DMKCBSM	Huntington disease	8A01.10	Phase 2	[11]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[12]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[15]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[15]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[16]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[17]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[18]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[19]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[15]

Drug(s) Affected By Neuronal acetylcholine receptor subunit alpha-7 (CHRNA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[3]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[25]
Carbachol	DMX9K8F	Glaucoma/ocular hypertension	9C61	Approved	[26]
Cotinine	DMCEZ1B	Insecticide	N.A.	Approved	[3]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Synaptic vesicle amine transporter (SLC18A2)	TTNZRI3	VMAT2_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Neuronal acetylcholine receptor subunit alpha-7 (CHRNA7)	OTBUSUTE	ACHA7_HUMAN	Drug Response	[3]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Design, synthesis and interaction at the vesicular monoamine transporter-2 of lobeline analogs: potential pharmacotherapies for the treatment of psychostimulant abuse. Curr Top Med Chem. 2011;11(9):1103-27.
• [3] Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant. Eur J Pharmacol. 1999 Feb 5;366(2-3):301-8. doi: 10.1016/s0014-2999(98)00909-1.
• [4] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8.
• [7] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [8] VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
• [9] NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Mov Disord. 2015 Oct;30(12):1681-7.
• [10] Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET. PLoS One. 2013 Sep 30;8(9):e75952.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [13] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [14] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [15] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [16] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [17] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [18] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [19] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.
• [20] Effects of cannabidiol on the function of 7-nicotinic acetylcholine receptors. Eur J Pharmacol. 2013 Nov 15;720(1-3):310-9. doi: 10.1016/j.ejphar.2013.10.011. Epub 2013 Oct 18.
• [21] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [22] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [23] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [24] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [25] Nicotine-induced Ca2+ signaling and down-regulation of nicotinic acetylcholine receptor subunit expression in the CEM human leukemic T-cell line. Life Sci. 2003 Mar 28;72(18-19):2155-8. doi: 10.1016/s0024-3205(03)00077-8.
• [26] Counteracting desensitization of human 7-nicotinic acetylcholine receptors with bispyridinium compounds as an approach against organophosphorus poisoning. Toxicol Lett. 2018 Sep 1;293:149-156. doi: 10.1016/j.toxlet.2017.12.005. Epub 2017 Dec 14.
• [27] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.