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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C22H27NO2.H2O4S
Molecular Weight 772.989
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOBELINE SULFATE

SMILES

OS(O)(=O)=O.CN1[C@H](C[C@H](O)C2=CC=CC=C2)CCC[C@@H]1CC(=O)C3=CC=CC=C3.CN4[C@H](C[C@H](O)C5=CC=CC=C5)CCC[C@@H]4CC(=O)C6=CC=CC=C6

InChI

InChIKey=GRZMOSSVIPFGFF-GNJLJDPWSA-N
InChI=1S/2C22H27NO2.H2O4S/c2*1-23-19(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;1-5(2,3)4/h2*2-7,9-12,19-21,24H,8,13-16H2,1H3;(H2,1,2,3,4)/t2*19-,20+,21-;/m00./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
1-Methyl-2,6-cis-distyrylpiperidine.
2009 Dec 9
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 SULFATE
MART.   MI   WHO-DD  
Common Name English
2-(6-(.BETA.-HYDROXYPHENETHYL)-1-METHYL-2-PIPERIDYL)ACETOPHENONE SULPHATE
Systematic Name English
LOBELINE SULFATE [MART.]
Common Name English
2-(6-(.BETA.-HYDROXYPHENETHYL)-1-METHYL-2-PIPERIDYL)ACETOPHENONE SULFATE
Systematic Name English
LOBELINE SULPHATE
Common Name English
.ALPHA.-LOBELINE SULPHATE
Common Name English
INFLATINE SULFATE
Common Name English
.ALPHA.-LOBELINE SULFATE
Common Name English
2-((2R,6S)-6-((2S)-2-HYDROXY-2-PHENYLETHYL)-1-METHYL-2-PIPERIDINYL)-1-PHENYLETHANONE SULFATE
Systematic Name English
INFLATINE SULPHATE
Common Name English
Lobeline sulfate [WHO-DD]
Common Name English
2-((2R,6S)-6-((2S)-2-HYDROXY-2-PHENYLETHYL)-1-METHYL-2-PIPERIDINYL)-1-PHENYLETHANONE SULPHATE
Systematic Name English
LOBELINE SULFATE [MI]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 310.544
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
Code System Code Type Description
EVMPD
SUB02962MIG
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
ECHA (EC/EINECS)
205-151-8
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
SMS_ID
100000086131
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
MERCK INDEX
m6879
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID80158452
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
FDA UNII
4CJ480V2HP
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
PUBCHEM
120636
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY
CAS
134-64-5
Created by admin on Fri Dec 15 15:19:22 GMT 2023 , Edited by admin on Fri Dec 15 15:19:22 GMT 2023
PRIMARY