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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H27NO2
Molecular Weight 337.4561
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOBELINE

SMILES

CN1[C@@]([H])(CCC[C@]1([H])CC(=O)c2ccccc2)C[C@@]([H])(c3ccccc3)O

InChI

InChIKey=MXYUKLILVYORSK-HBMCJLEFSA-N
InChI=1S/C22H27NO2/c1-23-19(15-21(24)17-9-4-2-5-10-17)13-8-14-20(23)16-22(25)18-11-6-3-7-12-18/h2-7,9-12,19-21,24H,8,13-16H2,1H3/t19-,20+,21-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12875893 | https://www.ncbi.nlm.nih.gov/pubmed/12604705 | https://clinicaltrials.gov/ct2/show/record/NCT00664703 | https://clinicaltrials.gov/ct2/show/study/NCT00519259

Lobeline is an alkaloid found in "Indian tobacco" (Lobelia inflata), "Devil's tobacco" (Lobelia tupa), "cardinal flower" (Lobelia cardinalis), "great lobelia" (Lobelia siphilitica), and Hippobroma longiflora. Additionally, it is also found in Lobelia Chinensis. In its pure form, it is a white amorphous powder which is freely soluble in water. Lobeline has been sold, in tablet form, for use as a smoking cessation aid, and may have application in the treatment of other drug addictions such as addiction to amphetamines, cocaine, or alcohol. Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand, which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine. It also inhibits the reuptake of dopamine and serotonin and acts as a mixed agonist-antagonist at nicotinic acetylcholine receptors to which it binds at the subunit interfaces of the extracellular domain. It is also an antagonist at μ-opioid receptors. It seems to be a P-glycoprotein inhibitor, according to at least one study. It has been hypothesized that P-glycoprotein inhibition reduces chemotherapeutic resistance in cancer, presumably affecting any substrates of P-gp.

CNS Activity

Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/12604705

Originator

Sources: Okayama Igakkai Zasshi Volume 39, Pages 1985-6, 1929

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
470.0 nM [Ki]
4.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
0.008 g 4 times / day multiple, oral
Studied dose
Dose: 0.008 g, 4 times / day
Route: oral
Route: multiple
Dose: 0.008 g, 4 times / day
Sources:
healthy, 28 years
n = 5
Health Status: healthy
Age Group: 28 years
Sex: M
Population Size: 5
Sources:
59 ug/kg single, intravenous
Highest studied dose
Dose: 59 ug/kg
Route: intravenous
Route: single
Dose: 59 ug/kg
Sources:
unhealthy, 45 years
n = 1
Health Status: unhealthy
Age Group: 45 years
Sex: M
Population Size: 1
Sources:
Other AEs: Cough...
AEs

AEs

AESignificanceDosePopulation
Cough
59 ug/kg single, intravenous
Highest studied dose
Dose: 59 ug/kg
Route: intravenous
Route: single
Dose: 59 ug/kg
Sources:
unhealthy, 45 years
n = 1
Health Status: unhealthy
Age Group: 45 years
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
yes [IC50 0.12 uM]
yes [Inhibition 20 uM]
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A-85380 and epibatidine each interact with disparate spinal nicotinic receptor subtypes to achieve analgesia and nociception.
2001 Apr
A specific anti-aggressive effect of repeatedly administered lobeline.
2002 Jul
Indirect trapping of the retroconjugate addition reaction intermediate involved in the epimerization of lobeline: application to the synthesis of (-)-sedamine.
2004 Nov 26
Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors.
2006 Oct 1
Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists.
2007 Jul 10
The exceptional hydrogen-bond properties of neutral and protonated lobeline.
2007 Jul 19
Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: applications to the total synthesis of alkaloids.
2008 Oct 15
(2S,6S)-1-Methyl-2,6-trans-distyryl-piperidinium chloride.
2009 Dec 9
1-Methyl-2,6-cis-distyrylpiperidine.
2009 Dec 9
Synthesis of (-)-lobeline via enzymatic desymmetrization of lobelanidine.
2009 Mar 1
Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperones.
2010 Apr 21
Patents

Patents

Sample Use Guides

In Vivo Use Guide
linical studies of lobeline for smoking withdrawal administered doses of 5 mg twice a day, with 0.5 mg lozenges used in addition when the urge to smoke was perceived
Route of Administration: Oral
Inhibition of [3H]-DA uptake was conducted in a preparation of isolated synaptic vesicles rat striata were homogenized with 10 strokes of a Teflon pestle homogenizer in 14 ml of 0.32 M sucrose solution. Homogenate was centrifuged (, and the resulting supernatant was centrifuged again). The pellet was resuspended in 2 ml of 0.32 M sucrose solution and subjected to osmotic shock by adding 7 ml of ice-cold water to the preparation, followed by the immediate restoration of osmolarity by adding 900 mkl of 0.25M HEPES buffer and 900 mkl of 1.0 M potassium tartrate solution. Samples were centrifuged, and the resulting supernatant was centrifuged again, followed by the addition of 100 mkl of 10 mM MgSO4, 100 mkl of 0.25 M HEPES and 100 mkl of 1.0 M potassium tartrate solution prior to the final centrifugation. The final pellet was resuspended in 2.4 ml of assay buffer. Aliquots of the vesicular suspension were added to tubes containing assay buffer, various concentrations of Lobeline (0.1 nM – 10 mM) and 0.1 PM [3H]-DA in a final volume of 500 Pl. Nonspecific uptake was determined in the presence of Ro4-1284 (10 mkM). Reactions were terminated by filtration, and radioactivity retained by the filters was determined by liquid scintillation spectroscopy
Name Type Language
LOBELINE
INN   MI   WHO-DD  
INN  
Official Name English
.ALPHA.-LOBELINE
Common Name English
LOBELINE [WHO-DD]
Common Name English
LOBELINUM [HPUS]
Common Name English
LOBELINUM
HPUS  
Common Name English
NSC-757421
Code English
2-((2R,6S)-6-((2S)-2-HYDROXY-2-PHENYLETHYL)-1-METHYL-2-PIPERIDINYL)-1-PHENYLETHANONE
Systematic Name English
2-(6-(.BETA.-HYDROXYPHENETHYL)-1-METHYL-2-PIPERIDYL)ACETOPHENONE
Systematic Name English
LOBELINE [INN]
Common Name English
LOBELINE [MI]
Common Name English
INFLATINE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C73579
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
WHO-VATC QV04CV01
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
Code System Code Type Description
PUBCHEM
101616
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
RXCUI
6464
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY RxNorm
INN
394
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
CAS
90-69-7
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
ECHA (EC/EINECS)
202-012-3
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
EPA CompTox
90-69-7
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
EVMPD
SUB08541MIG
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL2103769
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
MESH
D008120
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
MERCK INDEX
M6879
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB05137
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
FDA UNII
D0P25S3P81
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY
NCI_THESAURUS
C93261
Created by admin on Fri Jun 25 21:53:49 UTC 2021 , Edited by admin on Fri Jun 25 21:53:49 UTC 2021
PRIMARY