Stereochemistry | ABSOLUTE |
Molecular Formula | C22H27NO2 |
Molecular Weight | 337.4553 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1[C@H](C[C@H](O)C2=CC=CC=C2)CCC[C@@H]1CC(=O)C3=CC=CC=C3
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
Molecular Formula | C22H27NO2 |
Molecular Weight | 337.4553 |
Charge | 0 |
Count |
MOL RATIO
1 MOL RATIO (average) |
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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
Originator
Approval Year
Doses
AEs
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Tox targets
Sourcing
PubMed
Patents
Sample Use Guides
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