Lobeline: Difference between revisions

{{Drugbox

| verifiedrevid = 408578393

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

| image = Lobeline.svg

| width = 240

| routes_of_administration =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = <!-- blanked - oldvalue: 90-69-7 -->

| PubChem = 3945

| ChemSpiderID = 3808

| UNII_Ref = {{fdacite|changed|FDA}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 15476

| molecular_weight = 337.455

| smiles = O=C(c1ccccc1)CC3N(C)C(CC(O)c2ccccc2)CCC3

| InChI = 1/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

| InChIKey = MXYUKLILVYORSK-UHFFFAOYAY

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = MXYUKLILVYORSK-UHFFFAOYSA-N

'''Lobeline''' is a [[natural product|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,<ref>{{cite journal |author=Stead L, Hughes J |title=Lobeline for smoking cessation |journal=Cochrane Database Syst Rev |volume= |issue= 2|pages=CD000124 |year=2000 |pmid=10796490 |doi=10.1002/14651858.CD000124}}</ref><ref>Marlow SP, Stoller JK. Smoking cessation. ''Respiratory Care''. 2003 Dec;48(12):1238-56. PMID 14651764</ref><ref>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</ref> and may have application in the treatment of other drug addictions such as addiction to amphetamines,<ref>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</ref><ref>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</ref> cocaine<ref>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</ref> or alcohol.<ref>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</ref>

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

{{Reflist|2}}

{{Cholinergics}}

{{Dopaminergics}}

{{Serotonergics}}

[[Category:Opiates]]

[[Category:Alkaloids]]

[[Category:Piperidines]]

[[de:Lobelin]]

[[es:Lobelina]]

[[ja:ロベリン]]

[[pl:Lobelina]]

[[ru:Лобелин]]

[[sq:Lobelina]]