Anatabine: Difference between revisions

{{short description|Chemical compound}}

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| ChEBI = 2705

| ChEMBL = 3640772

| KEGG = C10126

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| PubChem = 11388

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'''Anatabine''' (uh-nat-uh-been,-bin) is one of the minor [[alkaloid]]s found in plants in the family [[Solanaceae]], which includes the [[tobacco plant]] and [[tomato]]. Commercial tobacco plants typically produce alkaloids at levels between 2% and 4% of total dry weight,<ref>{{cite journal | vauthors = Laszlo C, Kaminski K, Guan H, Fatarova M, Wei J, Bergounioux A, Schlage WK, Schorderet-Weber S, Guy PA, Ivanov NV, Lamottke K, Hoeng J | title = Fractionation and Extraction Optimization of Potentially Valuable Compounds and Their Profiling in Six Varieties of Two ''Nicotiana'' Species | journal = Molecules | volume = 27 | issue = 22 | page = 8105 | date = November 2022 | pmid = 36432206 | pmc = 9694777 | doi = 10.3390/molecules27228105 | doi-access = free }}</ref> with [[nicotine]] accounting for about 90% of the total alkaloid content, and the related compounds anatabine, [[nornicotine]], and [[anabasine]] making up nearly all the rest.<ref name=Dewey>{{cite journal | vauthors = Dewey RE, Xie J | title = Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum | journal = Phytochemistry | volume = 94 | pages = 10–27 | date = October 2013 | pmid = 23953973 | doi = 10.1016/j.phytochem.2013.06.002 | bibcode = 2013PChem..94...10D }}</ref> These compounds are thought to be biologically active, and part of plants' natural defense system against insects.<ref name=Dewey/>

Anatabine has [[anti-inflammatory]] activity partly through inhibition of [[STAT3]] phosphorylation in vitro and in vivo.<ref name="pmid23178521">{{cite journal |vauthors=Paris D, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M |title=Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation |journal=[[European Journal of Pharmacology]] |volume=698 |issue=1–3 |pages=145–53 |date=January 2013 |pmid=23178521 |doi=10.1016/j.ejphar.2012.11.017 |issn=}}</ref>

== Pharmacology ==

On a [[biochemical]] level, it appears to be active against certain [[nicotinic acetylcholine receptors]].<ref name=Mello/>

==Commercial development==

[[Star Scientific]] developed and sold the compound as a [[dietary supplement]] primarily through GNC up until mid 2014. Subsequently, Rock Creek Pharmaceuticals (formerly a subsidiary of [[Star Scientific]]), headquartered in Florida, began developing anatabine as a [[pharmaceutical drug|drug]].<ref name=Forbes>{{cite web | first = David | last = Kroll | work = Forbes | date = 31 January 2014 | url = https://www.forbes.com/sites/davidkroll/2014/01/31/whats-the-dope-on-anatabine-in-star-scientifics-anatabloc-and-cigrx/ | title = The McDonnell Scandal: What's The Dope Behind Star Scientific Supplement Products? }}</ref><ref name=Gabriel>{{cite web | first = Trip | last = Gabriel | work = New York Times | date = 21 January 2014 | url = https://www.nytimes.com/2014/01/22/us/former-virginia-governor-and-his-wife-are-indicted.html | title = Ex-Governor of Virginia Is Indicted on Charges Over Loans and Gifts }}</ref> The dietary supplements were known as Anatabloc and CigRx; the company has also marketed cosmetics with the Anatabloc brand.<ref name=Forbes/> Rock Creek had been working on synthetic methods to scale up production of anatabine and has funded [[Pre-clinical development|pre-clinical]] and [[clinical research|clinical]] research in several [[Indication (medicine)|indications]].<ref name=Forbes/>

In 2013 the FDA warned Star Scientific for unlawfully promoting CigRx and Anatabloc before anatabine was proved to be safe.<ref>{{cite news | url = http://washington.cbslocal.com/2013/12/31/fda-says-star-scientific-illegally-marketing-products/ | title = FDA Says Star Scientific Illegally Marketing Products | work = CBS News | date = December 31, 2013}}</ref><ref>[https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm379639.htm FDA Warning Letter]</ref> Subsequently, new management and a mostly new board under the banner of Rock Creek Pharmaceuticals withdrew the dietary supplement because of the FDA's concerns.

In 2013, Star Scientific became embroiled in political scandal, when news broke that the governor of Virginia, [[Bob McDonnell]], and his wife had received significant loans and gifts from [[Jonnie Williams]] Sr, the CEO of the company. They were found to have helped the company in several ways like arranging meetings with top officials and giving special favors from the state government.<ref name=Gabriel/> Williams resigned in 2014 and the company changed its name and restructured its board and management at the end of 2013 due to the scandal.<ref name=Forbes/>

However, the accumulated legal costs from the defense of Jonnie Williams in the McDonnell scandal overwhelmed the company’s finances and it filed for bankruptcy in 2016.<ref>{{Cite web|url=http://www.biospace.com/News/with-a-history-of-political-corruption-rock-creek/434072|title=With a History of Political Corruption Rock Creek Pharma Files for Bankruptcy|website=www.biospace.com|access-date=2017-08-17}}</ref> As a consequence, the development and clinical trials of anatabine were halted indefinitely.

== Research ==

Anatabine has been studied in animal models and in cells to see if it might be useful for treating [[nicotine addiction]] and [[inflammation]], and has been studied in models of diseases characterized by inflammation, such as [[Alzheimer's disease]],<ref name="pmid26230317">{{cite journal |vauthors=Verma M, Beaulieu-Abdelahad D, Ait-Ghezala G, Li R, Crawford F, Mullan M, Paris D |title=Correction: Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD |journal=[[PLOS One]] |volume=10 |issue=7 |pages=e0134776 |date=2015 |pmid=26230317 |pmc=4521847 |doi=10.1371/journal.pone.0134776 |issn=|doi-access=free |bibcode=2015PLoSO..1034776V }}</ref> [[thyroiditis]],<ref>{{cite journal | vauthors = Schmeltz LR, Blevins TC, Aronoff SL, Ozer K, Leffert JD, Goldberg MA, Horowitz BS, Bertenshaw RH, Troya P, Cohen AE, Lanier RK, Wright C | display-authors = 6 | title = Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 99 | issue = 1 | pages = E137-42 | date = January 2014 | pmid = 24178792 | pmc = 3928963 | doi = 10.1210/jc.2013-2951 }}</ref> and [[multiple sclerosis]].<ref name=Mello>{{cite journal | vauthors = Mello NK, Fivel PA, Kohut SJ, Caine SB | title = Anatabine significantly decreases nicotine self-administration | journal = Experimental and Clinical Psychopharmacology | volume = 22 | issue = 1 | pages = 1–8 | date = February 2014 | pmid = 24490707 | doi = 10.1037/a0035409 | s2cid = 15879738 }} Note: content is supported by discussion section which provides a brief review of research to date.</ref> Anatabine cream was helpful in managing mild to moderate [[rosacea]].<ref name="pmid24348385">{{cite journal |vauthors=Lanier RK, Cohen AE, Weinkle SH |title=Effects of a facial cream containing the minor alkaloid anatabine on improving the appearance of the skin in mild to moderate rosacea: an open-label case series study |journal=[[Case Reports in Dermatology]] |volume=5 |issue=3 |pages=347–56 |date=2013 |pmid=24348385 |pmc=3861860 |doi=10.1159/000357019|issn=}}</ref> An internet based survey showed 82% users reported a benefit from anatabine supplementation for one or more joint pain conditions.<ref name="pmid24250235">{{cite journal |vauthors=Lanier RK, Gibson KD, Cohen AE, Varga M |title=Effects of dietary supplementation with the solanaceae plant alkaloid anatabine on joint pain and stiffness: results from an internet-based survey study |journal=[[Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders]] |volume=6 |issue= |pages=73–84 |date=2013 |pmid=24250235 |pmc=3825642 |doi=10.4137/CMAMD.S13001 |issn=}}</ref>

== See also ==

* [[Anatalline]]

* [[Anabaseine]]

* [[Myosmine]]

[[Category:Pyridine alkaloids]]

[[Category:Alkaloids found in Solanaceae]]

[[Category:3-Pyridyl compounds]]