Lobeline

Drugbox
IUPAC_name = 2- [6-(2-hydroxy-2-phenyl-ethyl)-1-methyl-2-piperidyl] -1-phenyl-ethanone

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CAS_number= 90-69-7
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PubChem= 3945
DrugBank=
C=22 | H=27 | N=1 | O=2
molecular_weight = 337.455
smiles = CN1C(CCCC1CC(=O)C2=CC=CC=C2)CC(C3=CC=CC=C3)O
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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, [cite journal |author=Stead L, Hughes J |title=Lobeline for smoking cessation |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD000124 |year=2000 |pmid=10796490 |doi=10.1002/14651858.CD000124] [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] and may have application in the treatment of other drug addictions such as addiction to amphetamines [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. 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] or cocaine. [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]

Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand, [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. 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] which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine. [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] It also inhibits the reuptake of dopamine and serotonin, [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] and acts as a mixed agonist-antagonist at nicotinic acetylcholine receptors [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] and an antagonist at μ-opioid receptors. [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]

References