Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H27NO2.ClH |
Molecular Weight | 373.916 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN1[C@H](C[C@H](O)C2=CC=CC=C2)CCC[C@@H]1CC(=O)C3=CC=CC=C3
InChI
InChIKey=MKMYPTLXLWOUSO-NFQNBQCWSA-N
InChI=1S/C22H27NO2.ClH/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;1H/t19-,20+,21-;/m0./s1
DescriptionSources: https://www.drugs.com/npp/lobelia.htmlCurator'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
Sources: https://www.drugs.com/npp/lobelia.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12875893
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/12604705
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4828 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19691331 |
470.0 nM [Ki] | ||
Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26142318 |
4.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/18222670/ Page: 3.0 |
no | |||
Page: 15.0 |
yes [IC50 0.12 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18222670/ Page: 3.0 |
yes [Inhibition 20 uM] |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/20734202/ Page: 1.0 |
PubMed
Title | Date | PubMed |
---|---|---|
A-85380 and epibatidine each interact with disparate spinal nicotinic receptor subtypes to achieve analgesia and nociception. | 2001 Apr |
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The variability and repeatability of indices derived from the single-breath diagram for CO2 in horses with chronic obstructive pulmonary disease and the effect of lobelin hydrochloride on these indices. | 2001 Jul |
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A specific anti-aggressive effect of repeatedly administered lobeline. | 2002 Jul |
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Indirect trapping of the retroconjugate addition reaction intermediate involved in the epimerization of lobeline: application to the synthesis of (-)-sedamine. | 2004 Nov 26 |
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Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors. | 2006 Oct 1 |
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Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists. | 2007 Jul 10 |
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The exceptional hydrogen-bond properties of neutral and protonated lobeline. | 2007 Jul 19 |
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Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: applications to the total synthesis of alkaloids. | 2008 Oct 15 |
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(2S,6S)-1-Methyl-2,6-trans-distyryl-piperidinium chloride. | 2009 Dec 9 |
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1-Methyl-2,6-cis-distyrylpiperidine. | 2009 Dec 9 |
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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
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/npp/lobelia.html
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19691331
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
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SUB14389MIG
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DTXSID10928382
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96J834CB88
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CHEMBL2103769
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101615
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m6879
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205-150-2
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134-63-4
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ACTIVE MOIETY
SUBSTANCE RECORD