Anatabine

Last updated
Anatabine
Anatabine.svg
Identifiers
  • [2R,(+)]-1,2,3,6-Tetrahydro-2,3'-bipyridine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H12N2
Molar mass 160.220 g·mol−1
3D model (JSmol)
  • c1cc(cnc1)[C@@H]2CC=CCN2
  • InChI=1S/C10H12N2/c1-2-7-12-10(5-1)9-4-3-6-11-8-9/h1-4,6,8,10,12H,5,7H2/t10-/m0/s1 Yes check.svgY
  • Key:SOPPBXUYQGUQHE-JTQLQIEISA-N Yes check.svgY
   (verify)

Anatabine (uh-nat-uh-been,-bin) is one of the minor alkaloids 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, 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. [1] These compounds are thought to be biologically active, and part of plants' natural defense system against insects. [1]

Contents

Anatabine has anti-inflammatory activity partly through inhibition of STAT3 phosphorylation in vitro and in vivo. [2]

Pharmacology

On a biochemical level, it appears to be active against certain nicotinic acetylcholine receptors. [3]

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 drug. [4] [5] The dietary supplements were known as Anatabloc and CigRx; the company has also marketed cosmetics with the Anatabloc brand. [4] Rock Creek had been working on synthetic methods to scale up production of anatabine and has funded pre-clinical and clinical research in several indications. [4]

In 2013 the FDA warned Star Scientific for unlawfully promoting CigRx and Anatabloc before anatabine was proved to be safe. [6] [7] 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. [5] 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. [4]

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. [8] 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, [9] thyroiditis, [10] and multiple sclerosis. [3] Anatabine cream was helpful in managing mild to moderate rosacea. [11] An internet based survey showed 82% users reported a benefit from anatabine supplementation for one or more joint pain conditions. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Niacin</span> Organic compound and a form of vitamin B3

Niacin, also known as nicotinic acid, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortified packaged foods, meat, poultry, red fish such as tuna and salmon, lesser amounts in nuts, legumes and seeds. Niacin as a dietary supplement is used to treat pellagra, a disease caused by niacin deficiency. Signs and symptoms of pellagra include skin and mouth lesions, anemia, headaches, and tiredness. Many countries mandate its addition to wheat flour or other food grains, thereby reducing the risk of pellagra.

<span class="mw-page-title-main">Nicotine</span> Chemical stimulant produced by some plants

Nicotine is a naturally produced alkaloid in the nightshade family of plants and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits where it acts as a receptor antagonist.

<span class="mw-page-title-main">Dietary supplement</span> Product providing additional nutrients

A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources, or that are synthetic. The classes of nutrient compounds in supplements include vitamins, minerals, fiber, fatty acids, and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, and so are not nutrients per se, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, such as collagen from chickens or fish for example. These are also sold individually and in combination, and may be combined with nutrient ingredients. The European Commission has also established harmonized rules to help insure that food supplements are safe and appropriately labeled.

<i>Atropa belladonna</i> Species of toxic flowering plant in the nightshade family.

Atropa belladonna, commonly known as belladonna or deadly nightshade, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and aubergine (Eggplant). It is native to Europe and Western Asia, including Turkey. Its distribution extends from Ireland in the west to western Ukraine and the Iranian province of Gilan in the east. It is also naturalised or introduced in some parts of Canada, North Africa and the United States.

<span class="mw-page-title-main">Ephedra (medicine)</span> Medicinal preparation from the plant Ephedra sinica

Ephedra is a medicinal preparation from the plant Ephedra sinica. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the soma plant of Indo-Iranian religion. It has been used in traditional Chinese medicine, in which it is referred to as Ma Huang, for more than 2,000 years. Native Americans and Mormon pioneers drank a tea brewed from other Ephedra species, called "Mormon tea" and "Indian tea".

<span class="mw-page-title-main">Herbal medicine</span> Study and use of supposed medicinal properties of plants

Herbal medicine is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. With worldwide research into pharmacology, some herbal medicines have been translated into modern remedies, such as the anti-malarial group of drugs called artemisinin isolated from Artemisia annua, a herb that was known in Chinese medicine to treat fever. There is limited scientific evidence for the safety and efficacy of many plants used in 21st-century herbalism, which generally does not provide standards for purity or dosage. The scope of herbal medicine sometimes include fungal and bee products, as well as minerals, shells and certain animal parts.

<span class="mw-page-title-main">Nootropic</span> Compound intended to improve cognitive function

Nootropics are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.

<span class="mw-page-title-main">Yohimbine</span> Chemical compound

Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree Pausinystalia johimbe; also from the bark of the unrelated South American tree Aspidosperma quebracho-blanco. Yohimbine is an α2-adrenergic receptor antagonist, and has been used in a variety of research projects. It is a veterinary drug used to reverse sedation in dogs and deer.

<span class="mw-page-title-main">Medicinal plants</span> Plants or derivatives used to treat medical conditions in humans or animals

Medicinal plants, also called medicinal herbs, have been discovered and used in traditional medicine practices since prehistoric times. Plants synthesize hundreds of chemical compounds for various functions, including defense and protection against insects, fungi, diseases, and herbivorous mammals.

<i>Mitragyna speciosa</i> Plant species, recreational drug (kratom)

Mitragyna speciosa is a tropical evergreen tree in the coffee family native to Southeast Asia. It is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where it has been used in herbal medicine since at least the 19th century. It has also historically been used for chewing, smoking, and tea. Kratom has opiate properties and some stimulant-like effects.

<span class="mw-page-title-main">Galantamine</span> Neurological medication

Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.

Nutraceutical is a marketing term used to imply a pharmaceutical effect from a compound or food product that has not been scientifically confirmed or approved to have clinical benefits. In the United States, nutraceuticals are unregulated, existing in the same category as dietary supplements and food additives by the Food and Drug Administration (FDA), under the authority of the Federal Food, Drug, and Cosmetic Act.

<i>Bacopa monnieri</i> Species of aquatic plant

Bacopa monnieri is a perennial, creeping herb native to the wetlands of southern and Eastern India, Australia, Europe, Africa, Asia, and North and South America. It is known by the common names water hyssop, waterhyssop, brahmi, thyme-leafed gratiola, herb of grace, and Indian pennywort. Bacopa monnieri is used in Ayurveda. In 2019, the US Food and Drug Administration (FDA) warned manufacturers of dietary supplement products containing Bacopa monnieri against making illegal and unproven claims that the herb can treat various diseases.

<span class="mw-page-title-main">Zeaxanthin</span> Chemical compound

Zeaxanthin is one of the most common carotenoids in nature, and is used in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika, corn, saffron, goji (wolfberries), and many other plants and microbes their characteristic color.

<span class="mw-page-title-main">Vinpocetine</span> Chemical compound

Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group. Vincamine is extracted from either the seeds of Voacanga africana or the leaves of Vinca minor.

<span class="mw-page-title-main">Anabasine</span> Chemical compound

Anabasine is a pyridine and piperidine alkaloid found in the Tree Tobacco plant, as well as in the close relative of the common tobacco plant. It is a structural isomer of, and chemically similar to, nicotine. Its principal (historical) industrial use is as an insecticide.

<span class="mw-page-title-main">Picamilon</span> Chemical compound

Picamilon is a drug formed by a synthetic combination of niacin and γ-aminobutyric acid (GABA). It was developed in the Soviet Union in 1969 and further studied in both Russia and Japan as a prodrug of GABA.

<i>Vachellia rigidula</i> Species of plant

Vachellia rigidula, commonly known as blackbrush acacia or chaparro prieto, and also known as Acacia rigidula, is a species of shrub or small tree in the legume family, Fabaceae. Its native range stretches from Texas in the United States south to central Mexico. This perennial is not listed as being threatened. It reaches a height of 5–15 feet (1.5–4.6 m). Blackbrush acacia grows on limestone hillsides and canyons.

<span class="mw-page-title-main">Solanaceae</span> Family of flowering plants that includes tomatoes, potatoes and tobacco

The Solanaceae, or the nightshades, are a family of flowering plants that ranges from annual and perennial herbs to vines, lianas, epiphytes, shrubs, and trees, and includes a number of agricultural crops, medicinal plants, spices, weeds, and ornamentals. Many members of the family contain potent alkaloids, and some are highly toxic, but many—including tomatoes, potatoes, eggplant, bell and chili peppers—are used as food. The family belongs to the order Solanales, in the asterid group and class Magnoliopsida (dicotyledons). The Solanaceae consists of about 98 genera and some 2,700 species, with a great diversity of habitats, morphology and ecology.

<span class="mw-page-title-main">Mitragynine</span> Alkaloid analgesic compound

Mitragynine is an indole-based alkaloid and the most abundant active alkaloid in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. The total alkaloid concentration in dried leaves ranges from 0.5 to 1.5%. In Thai varieties, mitragynine is the most abundant component while 7-hydroxymitragynine is a minor constituent. In Malaysian kratom varieties, mitragynine is present at lower concentration. Such preparations are orally consumed and typically involve dried kratom leaves which are brewed into tea or ground and placed into capsules. Mitragynine consumption for medicinal and recreation purposes dates back centuries, although early use was primarily limited to Southeast Asian countries such as Indonesia and Thailand where the plant grows indigenously. Recently, mitragynine use has spread throughout Europe and the Americas as both a recreational and medicinal drug. While research into the effects of kratom have begun to emerge, investigations on the active compound mitragynine are less common.

References

  1. 1 2 Dewey RE, Xie J (October 2013). "Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum". Phytochemistry. 94: 10–27. Bibcode:2013PChem..94...10D. doi:10.1016/j.phytochem.2013.06.002. PMID   23953973.
  2. Paris D, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M (January 2013). "Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation". European Journal of Pharmacology . 698 (1–3): 145–53. doi:10.1016/j.ejphar.2012.11.017. PMID   23178521.
  3. 1 2 Mello NK, Fivel PA, Kohut SJ, Caine SB (February 2014). "Anatabine significantly decreases nicotine self-administration". Experimental and Clinical Psychopharmacology. 22 (1): 1–8. doi:10.1037/a0035409. PMID   24490707. S2CID   15879738. Note: content is supported by discussion section which provides a brief review of research to date.
  4. 1 2 3 4 Kroll D (31 January 2014). "The McDonnell Scandal: What's The Dope Behind Star Scientific Supplement Products?". Forbes.
  5. 1 2 Gabriel T (21 January 2014). "Ex-Governor of Virginia Is Indicted on Charges Over Loans and Gifts". New York Times.
  6. "FDA Says Star Scientific Illegally Marketing Products". CBS News. December 31, 2013.
  7. FDA Warning Letter
  8. "With a History of Political Corruption Rock Creek Pharma Files for Bankruptcy". www.biospace.com. Retrieved 2017-08-17.
  9. Verma M, Beaulieu-Abdelahad D, Ait-Ghezala G, Li R, Crawford F, Mullan M, Paris D (2015). "Correction: Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD". PLOS One . 10 (7): e0134776. Bibcode:2015PLoSO..1034776V. doi: 10.1371/journal.pone.0134776 . PMC   4521847 . PMID   26230317.
  10. Schmeltz LR, Blevins TC, Aronoff SL, Ozer K, Leffert JD, Goldberg MA, et al. (January 2014). "Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial". The Journal of Clinical Endocrinology and Metabolism. 99 (1): E137-42. doi:10.1210/jc.2013-2951. PMC   3928963 . PMID   24178792.
  11. Lanier RK, Cohen AE, Weinkle SH (2013). "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". Case Reports in Dermatology . 5 (3): 347–56. doi:10.1159/000357019. PMC   3861860 . PMID   24348385.
  12. Lanier RK, Gibson KD, Cohen AE, Varga M (2013). "Effects of dietary supplementation with the solanaceae plant alkaloid anatabine on joint pain and stiffness: results from an internet-based survey study". Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders . 6: 73–84. doi:10.4137/CMAMD.S13001. PMC   3825642 . PMID   24250235.