Lobeline

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Lobeline
Systematic (IUPAC) name
2-[6-(2-hydroxy-2-phenyl-ethyl)-1-methyl-2-piperidyl]-1-phenyl-ethanone
Identifiers
CAS number 90-69-7
ATC code  ?
PubChem 3945
Chemical data
Formula C22H27NO2 
Mol. mass 337.455
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?
Legal status
Routes  ?

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] or cocaine.[6]

Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand,[7][8][9] which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine.[10][11] It also inhibits the reuptake of dopamine and serotonin,[12] and acts as a mixed agonist-antagonist at nicotinic acetylcholine receptors[13][14] and an antagonist at μ-opioid receptors.[15]

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[edit] References

  1. ^ Stead L, Hughes J (2000). "Lobeline for smoking cessation". Cochrane Database Syst Rev: CD000124. doi:10.1002/14651858.CD000124. PMID 10796490. 
  2. ^ Marlow SP, Stoller JK. Smoking cessation. Respiratory Care. 2003 Dec;48(12):1238-56. PMID 14651764
  3. ^ 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
  4. ^ 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
  5. ^ 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
  6. ^ 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
  7. ^ 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
  8. ^ 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
  9. ^ 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
  10. ^ 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
  11. ^ 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
  12. ^ 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
  13. ^ 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
  14. ^ 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
  15. ^ 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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Drugs used in addictive disorders (N07B)
Nicotine dependence
Alcohol dependence
Opioid dependence
Stimulant dependence
Benzodiazepine dependence
Cocaine dependence
Sedative-Hypnotic dependence