Lobeline: Difference between revisions
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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{cs1 config|name-list-style=vanc}} |
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{{Infobox drug |
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| Verifiedfields = changed |
| Verifiedfields = changed |
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| Watchedfields = changed |
| Watchedfields = changed |
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| verifiedrevid = |
| verifiedrevid = 458947626 |
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| IUPAC_name = 2- |
| IUPAC_name = 2-((2''R'',6''S'')-6-((''S'')-2-Hydroxy-2-phenylethyl)-1-methylpiperidin-2-yl)-1-phenylethanone |
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| image = Lobeline.svg |
| image = Lobeline structure.svg |
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| width = |
| width = 200 |
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<!--Clinical data--> |
<!--Clinical data--> |
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| tradename = |
| tradename = |
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| Drugs.com = {{drugs.com|international|lobeline}} |
| Drugs.com = {{drugs.com|international|lobeline}} |
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| routes_of_administration = |
| routes_of_administration = |
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<!--Identifiers--> |
<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct| |
| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = |
| CAS_number = 90-69-7 |
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| ATCvet = yes |
| ATCvet = yes |
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| ATC_prefix = V04 |
| ATC_prefix = V04 |
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| ATC_suffix = CV01 |
| ATC_suffix = CV01 |
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| PubChem = |
| PubChem = 101616 |
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| ChEBI = 48723 |
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| DrugBank = DB05137 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = |
| ChemSpiderID = 91814 |
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| UNII_Ref = {{fdacite| |
| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = D0P25S3P81 |
| UNII = D0P25S3P81 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D02364 |
| KEGG = D02364 |
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| ChEMBL_Ref = {{ebicite| |
| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = |
| ChEMBL = 2103769 |
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=22 | H=27 | N=1 | O=2 |
| C=22 | H=27 | N=1 | O=2 |
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| melting_point = 130 |
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| molecular_weight = 337.455 |
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| melting_high = 131 |
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| smiles = O=C(c1ccccc1)CC3N(C)C(CC(O)c2ccccc2)CCC3 |
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| smiles = O=C(C[C@@H]1N([C@@H](CCC1)C[C@@H](C2=CC=CC=C2)O)C)C3=CC=CC=C3 |
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| 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 |
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| StdInChIKey = MXYUKLILVYORSK-UHFFFAOYSA-N |
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}} |
}} |
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'''Lobeline''' is a |
'''Lobeline''' is a piperidine [[alkaloid]] found in a variety of plants, particularly those in the genus ''[[Lobelia]]'', including Indian tobacco (''[[Lobelia inflata]]''), Devil's tobacco (''[[Lobelia tupa]]''), great lobelia (''[[Lobelia siphilitica]]''), ''[[Lobelia chinensis]]'', and ''[[Hippobroma longiflora]]''. In its pure form, it is a white amorphous powder which is freely soluble in water. |
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==Potential uses== |
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Lobeline has been |
Lobeline has been sold, in tablet form, for use as a [[smoking cessation]] aid, but scientific research has not provided supporting evidence for this use.<ref name=Cochrane>{{cite journal | vauthors = Stead LF, Hughes JR | title = Lobeline for smoking cessation | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 2 | pages = CD000124 | date = February 2012 | pmid = 22336780 | doi = 10.1002/14651858.CD000124.pub2 | pmc = 7043274 | quote = On the basis of the trials which have been published in the past sixty years there is no evidence that lobeline has any long term effect on smoking cessation.}}</ref><ref>{{cite journal | vauthors = Marlow SP, Stoller JK | title = Smoking cessation | journal = Respiratory Care | volume = 48 | issue = 12 | pages = 1238–54; discussion 1254–6 | date = December 2003 | pmid = 14651764 }}</ref><ref>{{cite journal | vauthors = Buchhalter AR, Fant RV, Henningfield JE | title = Novel pharmacological approaches for treating tobacco dependence and withdrawal: current status | journal = Drugs | volume = 68 | issue = 8 | pages = 1067–88 | year = 2008 | pmid = 18484799 | doi = 10.2165/00003495-200868080-00005 | s2cid = 46875770 }}</ref> Lobeline has also been studied for the treatment of other drug addictions such as addiction to amphetamines,<ref>{{cite journal | vauthors = Neugebauer NM, Harrod SB, Stairs DJ, Crooks PA, Dwoskin LP, Bardo MT | title = Lobelane decreases methamphetamine self-administration in rats | journal = European Journal of Pharmacology | volume = 571 | issue = 1 | pages = 33–8 | date = September 2007 | pmid = 17612524 | pmc = 2104779 | doi = 10.1016/j.ejphar.2007.06.003 }}</ref><ref>{{cite journal | vauthors = Eyerman DJ, Yamamoto BK | title = Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 312 | issue = 1 | pages = 160–9 | date = January 2005 | pmid = 15331654 | doi = 10.1124/jpet.104.072264 | s2cid = 19787823 }}</ref> cocaine,<ref>{{cite journal | vauthors = Polston JE, Cunningham CS, Rodvelt KR, Miller DK | title = Lobeline augments and inhibits cocaine-induced hyperactivity in rats | journal = Life Sciences | volume = 79 | issue = 10 | pages = 981–90 | date = August 2006 | pmid = 16765386 | doi = 10.1016/j.lfs.2006.05.006 }}</ref> or alcohol;<ref>{{cite journal | vauthors = Farook JM, Lewis B, Gaddis JG, Littleton JM, Barron S | title = Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice | journal = Physiology & Behavior | volume = 97 | issue = 3–4 | pages = 503–6 | date = June 2009 | pmid = 19268674 | doi = 10.1016/j.physbeh.2009.02.031 | s2cid = 23762679 }}</ref> however, there is limited clinical evidence of any [[efficacy]].<ref name=Cochrane/><ref>{{cite web | url = https://www.drugs.com/npp/lobelia.html | title = Lobelia | publisher = [[drugs.com]]}}</ref> |
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==Toxicity== |
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⚫ | Lobeline has multiple mechanisms of action, acting as a [[VMAT2]] ligand,<ref>Zheng G, Dwoskin LP, Crooks PA |
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Ingestion of lobeline may cause nausea, vomiting, diarrhea, coughing, dizziness, visual disturbances, hearing disturbances, mental confusion, weakness, slowed heart rate, increased blood pressure, increased breathing rate, tremors, and seizures.<ref name="drugs.com">{{cite web | url = https://www.drugs.com/npp/lobelia.html | title = Lobelia | publisher = drugs.com}}</ref><ref>{{cite web | url = http://www.rightdiagnosis.com/p/plant_poisoning_lobeline/symptoms.htm | title = Symptoms of Plant poisoning -- Lobeline }}</ref> Lobeline has a narrow [[therapeutic index]]: the potentially beneficial dose of lobeline is very close to the toxic dose.<ref name="drugs.com"/> |
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==Pharmacology== |
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⚫ | Lobeline has multiple mechanisms of action, acting as a [[VMAT2]] ligand,<ref>{{cite journal | vauthors = Zheng G, Dwoskin LP, Crooks PA | title = Vesicular monoamine transporter 2: role as a novel target for drug development | journal = The AAPS Journal | volume = 8 | issue = 4 | pages = E682-92 | date = November 2006 | pmid = 17233532 | pmc = 2751365 | doi = 10.1208/aapsj080478 }}</ref><ref>{{cite journal | vauthors = Zheng F, Zheng G, Deaciuc AG, Zhan CG, Dwoskin LP, Crooks PA | title = Computational neural network analysis of the affinity of lobeline and tetrabenazine analogs for the vesicular monoamine transporter-2 | journal = Bioorganic & Medicinal Chemistry | volume = 15 | issue = 8 | pages = 2975–92 | date = April 2007 | pmid = 17331733 | pmc = 2001191 | doi = 10.1016/j.bmc.2007.02.013 }}</ref><ref>{{cite journal | vauthors = Zheng G, Dwoskin LP, Deaciuc AG, Norrholm SD, Crooks PA | title = Defunctionalized lobeline analogues: structure-activity of novel ligands for the vesicular monoamine transporter | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 17 | pages = 5551–60 | date = August 2005 | pmid = 16107155 | pmc = 3617589 | doi = 10.1021/jm0501228 }}</ref> which stimulates [[dopamine]] release to a moderate extent when administered alone, but reduces the dopamine release caused by [[methamphetamine]].<ref>{{cite journal | vauthors = Wilhelm CJ, Johnson RA, Eshleman AJ, Janowsky A | title = Lobeline effects on tonic and methamphetamine-induced dopamine release | journal = Biochemical Pharmacology | volume = 75 | issue = 6 | pages = 1411–5 | date = March 2008 | pmid = 18191815 | pmc = 2435375 | doi = 10.1016/j.bcp.2007.11.019 }}</ref><ref>{{cite journal | vauthors = Wilhelm CJ, Johnson RA, Lysko PG, Eshleman AJ, Janowsky A | title = Effects of methamphetamine and lobeline on vesicular monoamine and dopamine transporter-mediated dopamine release in a cotransfected model system | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 310 | issue = 3 | pages = 1142–51 | date = September 2004 | pmid = 15102929 | doi = 10.1124/jpet.104.067314 | s2cid = 1315645 }}</ref> It also inhibits the [[reuptake]] of dopamine and [[serotonin]],<ref>{{cite journal | vauthors = Zheng G, Horton DB, Deaciuc AG, Dwoskin LP, Crooks PA | title = Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters | journal = Bioorganic & Medicinal Chemistry Letters | volume = 16 | issue = 19 | pages = 5018–21 | date = October 2006 | pmid = 16905316 | pmc = 3934794 | doi = 10.1016/j.bmcl.2006.07.070 }}</ref> and acts as a mixed [[agonist–antagonist]] at [[nicotinic acetylcholine receptor]]s<ref>{{cite journal | vauthors = Damaj MI, Patrick GS, Creasy KR, Martin BR | title = Pharmacology of lobeline, a nicotinic receptor ligand | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 282 | issue = 1 | pages = 410–9 | date = July 1997 | pmid = 9223582 }}</ref><ref>{{cite journal | vauthors = Miller DK, Harrod SB, Green TA, Wong MY, Bardo MT, Dwoskin LP | title = Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats | journal = Pharmacology, Biochemistry, and Behavior | volume = 74 | issue = 2 | pages = 279–86 | date = January 2003 | pmid = 12479946 | doi = 10.1016/s0091-3057(02)00996-6 | s2cid = 20510311 }}</ref> to which it binds at the subunit interfaces of the extracellular domain.<ref>PDB entry {{PDBe|2bys}}. {{cite journal | vauthors = Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, Bourne Y | title = Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations | journal = The EMBO Journal | volume = 24 | issue = 20 | pages = 3635–46 | date = October 2005 | pmid = 16193063 | pmc = 1276711 | doi = 10.1038/sj.emboj.7600828 }}</ref> It is also an [[receptor antagonist|antagonist]] at [[Mu Opioid receptor|μ-opioid receptors]].<ref>{{cite journal | vauthors = Miller DK, Lever JR, Rodvelt KR, Baskett JA, Will MJ, Kracke GR | title = Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists | journal = Drug and Alcohol Dependence | volume = 89 | issue = 2–3 | pages = 282–91 | date = July 2007 | pmid = 17368966 | doi = 10.1016/j.drugalcdep.2007.02.003 }}</ref> It seems to be a [[P-glycoprotein]] inhibitor, according to at least one study.<ref>{{cite journal | vauthors = Ma Y, Wink M | title = Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells | journal = Phytomedicine | volume = 15 | issue = 9 | pages = 754–8 | date = September 2008 | pmid = 18222670 | doi = 10.1016/j.phymed.2007.11.028 }}</ref> It has been hypothesized that P-glycoprotein inhibition reduces chemotherapeutic resistance in cancer,<ref>{{cite journal | vauthors = Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM | title = P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review | journal = Journal of Advanced Research | volume = 6 | issue = 1 | pages = 45–62 | date = January 2015 | pmid = 25685543 | pmc = 4293676 | doi = 10.1016/j.jare.2014.11.008 }}</ref> presumably affecting any substrates of P-gp. |
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Analogous compounds, such as [[lobelane]] (a minor alkaloid found in the same plants) and its synthetic derivatives have similar biological effects with somewhat different relative affinities to VMAT and other proteins.<ref name="pmid15121762">{{cite journal | vauthors = Miller DK, Crooks PA, Zheng G, Grinevich VP, Norrholm SD, Dwoskin LP | title = Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 310 | issue = 3 | pages = 1035–45 | date = September 2004 | pmid = 15121762 | doi = 10.1124/jpet.104.068098 | s2cid = 438066 }}</ref> A related alkaloid [[sedamine]],<ref>{{cite web | publisher = National Center for Biotechnology Information | work = PubChem Database | title = (-)-Sedamine, CID=442657 | url = https://pubchem.ncbi.nlm.nih.gov/compound/Sedamine | access-date = July 7, 2019 }}</ref> with only one 2-phenylethyl group on the [[piperidine]] ring and found in plants of genus [[sedum]], is known to be an inhibitor of pea seedlings amine oxidase,<ref name="pmid11916142">{{cite journal | vauthors = Adámková S, Frébort I, Sebela M, Pec P | title = Probing the active site of pea seedlings amine oxidase with optical antipodes of sedamine alkaloids | journal = Journal of Enzyme Inhibition | volume = 16 | issue = 4 | pages = 367–72 | date = October 2001 | pmid = 11916142 | doi = 10.1080/14756360109162385 | doi-access = free }}</ref> but its affinity to proteins such as the dopamine transporter has apparently not been tested. |
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== See also == |
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* [[Lobelanine]] |
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* [[Lobelanidine]] |
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== References == |
== References == |
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{{Reflist| |
{{Reflist|32em}} |
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{{Stimulants}} |
{{Stimulants}} |
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{{Antiaddictives}} |
{{Antiaddictives}} |
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{{Monoamine reuptake inhibitors}} |
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{{Cholinergics}} |
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{{Nicotinic acetylcholine receptor modulators}} |
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{{Dopaminergics}} |
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{{Opioid receptor modulators}} |
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{{Serotonergics}} |
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[[Category:Antidepressants]] |
[[Category:Antidepressants]] |
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[[Category:Nicotinic agonists]] |
[[Category:Nicotinic agonists]] |
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[[Category:Ketones]] |
[[Category:Ketones]] |
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[[Category:Mu-opioid receptor antagonists]] |
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[[de:Lobelin]] |
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[[Category:Piperidine alkaloids]] |
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[[es:Lobelina]] |
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[[ja:ロベリン]] |
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[[pl:Lobelina]] |
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[[ru:Лобелин]] |
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[[sq:Lobelina]] |