Lobeline
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| Systematic (IUPAC) name | |
| 2-((2R,6S)-6-((S)-2-hydroxy-2-phenylethyl)-1-methylpiperidin-2-yl)-1-phenylethanone | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | ? |
| Legal status | ? |
| Identifiers | |
| CAS number | 90-69-7  |
| ATCvet code | QV04CV01 |
| PubChem | CID 101616 |
| ChemSpider | 91814 |
| UNII | D0P25S3P81  |
| KEGG | D02364 |
| ChEMBL | CHEMBL15476 |
| Chemical data | |
| Formula | C22H27NO2 |
| Mol. mass | 337.455 |
| SMILES | eMolecules & PubChem |
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Lobeline is a natural alkaloid found in "Indian tobacco" (Lobelia inflata), "Devil's tobacco" (Lobelia tupa), "cardinal flower" (Lobelia cardinalis), "great lobelia" (Lobelia siphilitica), and Hippobroma longiflora. In its pure form it is a white amorphous powder which is freely soluble in water.
Lobeline has been used as a smoking cessation aid,[1][2][3] and may have application in the treatment of other drug addictions such as addiction to amphetamines,[4][5] cocaine[6] or alcohol.[7]
Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand,[8][9][10] which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine.[11][12] It also inhibits the reuptake of dopamine and serotonin,[13] and acts as a mixed agonist-antagonist at nicotinic acetylcholine receptors [14][15] to which it binds at the subunit interfaces of the extracellular domain. [16] and an antagonist at μ-opioid receptors.[17]
[edit] References
- ^ Stead LF, Hughes JR (2012). "Lobeline for smoking cessation". Cochrane Database Syst Rev 2: CD000124. doi:10.1002/14651858.CD000124.pub2. PMID 22336780.
- ^ Marlow SP, Stoller JK. Smoking cessation. Respiratory Care. 2003 Dec;48(12):1238-56. PMID 14651764
- ^ Buchhalter AR, Fant RV, Henningfield JE. Novel pharmacological approaches for treating tobacco dependence and withdrawal : current status. Drugs. 2008;68(8):1067-88. PMID 18484799
- ^ Neugebauer NM, Harrod SB, Stairs DJ, Crooks PA, Dwoskin LP, Bardo MT. Lobelane decreases methamphetamine self-administration in rats. European Journal of Pharmacology. 2007 Sep 24;571(1):33-8. doi:10.1016/j.ejphar.2007.06.003 PMID 17612524
- ^ Eyerman DJ, Yamamoto BK. Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum. Journal of Pharmacology and Experimental Therapeutics. 2005 Jan;312(1):160-9. PMID 15331654
- ^ Polston JE, Cunningham CS, Rodvelt KR, Miller DK. Lobeline augments and inhibits cocaine-induced hyperactivity in rats. Life Sciences. 2006 Aug 1;79(10):981-90. PMID 16765386
- ^ Farook JM, Lewis B, Gaddis JG, Littleton JM, Barron S. Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice. Physiology and Behavior. 2009 Jun 22;97(3-4):503-6. PMID 19268674
- ^ Zheng G, Dwoskin LP, Crooks PA. Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS Journal. 2006 Nov 10;8(4):E682-92. doi:10.1208/aapsj080478 PMID 17233532
- ^ Zheng F, Zheng G, Deaciuc AG, Zhan CG, Dwoskin LP, Crooks PA. Computational neural network analysis of the affinity of lobeline and tetrabenazine analogs for the vesicular monoamine transporter-2. Bioorganic and Medicinal Chemistry. 2007 Apr 15;15(8):2975-92. PMID 17331733
- ^ Zheng G, Dwoskin LP, Deaciuc AG, Norrholm SD, Crooks PA. Defunctionalized lobeline analogues: structure-activity of novel ligands for the vesicular monoamine transporter. Journal of Medicinal Chemistry. 2005 Aug 25;48(17):5551-60. PMID 16107155
- ^ Wilhelm CJ, Johnson RA, Eshleman AJ, Janowsky A. Lobeline effects on tonic and methamphetamine-induced dopamine release. Biochemical Pharmacology. 2008 Mar 15;75(6):1411-5. PMID 18191815
- ^ Wilhelm CJ, Johnson RA, Lysko PG, Eshleman AJ, Janowsky A. Effects of methamphetamine and lobeline on vesicular monoamine and dopamine transporter-mediated dopamine release in a cotransfected model system. Journal of Pharmacology and Experimental Therapeutics. 2004 Sep;310(3):1142-51. PMID 15102929
- ^ Zheng G, Horton DB, Deaciuc AG, Dwoskin LP, Crooks PA. Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters. Bioorganic and Medicinal Chemistry Letters. 2006 Oct 1;16(19):5018-21. PMID 16905316
- ^ Damaj MI, Patrick GS, Creasy KR, Martin BR. Pharmacology of lobeline, a nicotinic receptor ligand. Journal of Pharmacology and Experimental Therapeutics. 1997 Jul;282(1):410-9. PMID 9223582
- ^ Miller DK, Harrod SB, Green TA, Wong MY, Bardo MT, Dwoskin LP. Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Pharmacology, Biochemistry and Behaviour. 2003 Jan;74(2):279-86. PMID 12479946
- ^ PDB entry 2bys. Hansen et al. Structures of Aplysia Achbp Complexes with Nicotinic Agonists and Antagonists Reveal Distinctive Binding Interfaces and Conformations. 'EMBO J. 2005 24:23653-91. PMID 16193063
- ^ Miller DK, Lever JR, Rodvelt KR, Baskett JA, Will MJ, Kracke GR. Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists. Drug and Alcohol Dependence. 2007 Jul 10;89(2-3):282-91. PMID 17368966
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