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Vinpocetine

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	Not recommended
Routes of administration	Oral, intravenous
ATC code	N06BX18 (WHO)
Legal status
Legal status	US: Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in dietary supplements, food, or medicine is unlawful; otherwise uncontrolled. EU: Rx-only
Pharmacokinetic data
Bioavailability	56.6 ± 8.9%
Metabolism	hepatic
Elimination half-life	2.54 ± 0.48 hours
Excretion	renal
Identifiers
IUPAC name (3α,16α)-Eburnamenine-14-carboxylic acid ethyl ester
CAS Number	42971-09-5
PubChem CID	443955
IUPHAR/BPS	5285
ChemSpider	392007
UNII	543512OBTC
KEGG	D01371
ChEMBL	ChEMBL71752
CompTox Dashboard (EPA)	DTXSID5023740
ECHA InfoCard	100.050.917
Chemical and physical data
Formula	C22H26N2O2
Molar mass	350.462 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(OCC)C=4n1c3c(c2ccccc12)CCN53(C=4)(CCC5)CC
InChI InChI=1S/C22H26N2O2/c1-3-22-11-7-12-23-13-10-16-15-8-5-6-9-17(15)24(19(16)20(22)23)18(14-22)21(25)26-4-2/h5-6,8-9,14,20H,3-4,7,10-13H2,1-2H3/t20-,22+/m1/s1 Key:DDNCQMVWWZOMLN-IRLDBZIGSA-N
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Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group and by being the ethyl rather than the methyl ester of the underlying carboxylic acid. Vincamine is extracted from either the seeds of Voacanga africana or the leaves of Vinca minor (lesser periwinkle).

Medical uses

Vinpocetine has been used in many Asian and European countries for treatment of cerebrovascular disorders such as stroke and dementia for over three decades.

The FDA has tentatively ruled that vinpocetine, due to its synthetic nature and proposed therapeutic uses, is ineligible to be marketed as dietary supplement under the Federal Food, Drug, and Cosmetic Act. Despite this, vinpocetine remains widely available in dietary supplements often marketed as nootropics.

Vinpocetine does not fully support a benefit in either dementia or stroke. As of 2003, three controlled clinical trials had tested "older adults with memory problems".

Vinpocetine has also been studied for the prevention and recovery of acquired hearing loss in a phase II, longitudinal and prospective open clinical study on humans.

Side effects

Use during pregnancy may harm the baby or result in miscarriage.

Adverse effects of vinpocetine include flushing, nausea, dizziness, dry mouth, transient hypo- and hyper-tension, headaches, heartburn, and decreased blood pressure. FDA issued a statement in 2019 warning that "vinpocetine may cause a miscarriage or harm fetal development".

Mechanism of action

Vinpocetine’s mechanism of action has been postulated to involve three potential effects: blockage of sodium channels, reduction of cellular calcium influx, and antioxidant activity. Studies have also suggested that vinpocetine can inhibit PDE-1 in isolated rabbit aorta; inhibit IKK in vitro, preventing IκB degradation and the following translocation of NF-κB to the cell nucleus; and increase DOPAC, a metabolic breakdown product of dopamine, in isolated striatal nerve endings of rats.

Dietary supplement

The inclusion of vinpocetine in dietary supplements in the U.S. has come under scrutiny due to the lack of defined dosage parameters, unproven short- and long-term benefits, and risks to human health. In the U.S., vinpocetine supplements are marketed as sports supplements, brain enhancers, and weight loss supplements.

A 2015 analysis of 23 brands of vinpocetine dietary supplements sold at GNC and Vitamin Shoppe retail stores reported widespread labeling errors. Only 6 of the 23 supplement labels (26%) provided consumers with accurate dosages of vinpocetine (ranging from 0.3 to 32 mg per recommended daily serving), while 6 of 23 (26%) contained no vinpocetine at all, despite their labels claiming that the ingredient was in them. In total, 9 of the 23 products tested were mislabeled, and 17 of 23 (74%) did not provide any information on the quantity of vinpocetine.

In response to the study, then-senator Claire McCaskill, while at the time serving as the top Democrat on the Senate Special Committee on Aging, urged the FDA to suspend sales of vinpocetine supplements and asked 10 retailers to voluntarily stop selling vinpocetine products. McCaskill stated: "The way we regulate these supplements isn’t working—and it’s putting the lives and well-being of consumers at risk. We’ve seen products with false labels, tainted ingredients, wildly illegal claims, and, now, products containing synthesized ingredients that are classified as prescription drugs in other countries."

Lawsuits

Procera AVH is a dietary supplement containing undisclosed amounts of vinpocetine in combination with huperzine A and acetyl-l-carnitine. In 2012, manufacturer Brain Research Labs (BRL) agreed to pay $500,000 to settle a class action lawsuit which alleged that the company had falsely marketed Procera AVH as capable of improving brain function, in violation of the Consumer Fraud Act.

In July 2015, the U.S. Federal Trade Commission (FTC) ruled that marketing claims for Procera AVH, which promoted the product as a “solution” to memory loss and cognitive decline, were false, misleading, unsubstantiated, and in violation of the FTC Act. BRL and its affiliated companies Brain Power Partners, Brain Power Founders, and MedHealth Direct (all based in Laguna Beach, California) were fined $91 million. KeyView Labs, the Tampa, Florida-based company that purchased BRL in 2012, was fined $61 million. Also named in the FTC complaint were George Reynolds (aka Josh Reynolds), founder and chief science officer of BRL, and John Arnold, the sole officer and employee of MedHealth. The FTC complaint charged Reynolds with making deceptive expert endorsements for Procera AVH. The defendants in the case ultimately agreed to pay $1.4 million to settle the allegations of deceptive advertising brought by the FTC and California law enforcement officials. In addition, a permanent injunction barred the defendants from making similar deceptive claims about Procera AVH in the future and from misrepresenting the existence, results, or conclusions of any scientific study.

References

1. ^ Office of the Commissioner (3 June 2019). "Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine". FDA. Retrieved 5 June 2019.
2. "Vinpocetine in Dietary Supplements". FDA. February 22, 2023. Retrieved June 9, 2023.
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5. Hank S (7 September 2016). "FDA rules vinpocetine not a legal dietary ingredient despite successful NDI filings". NutraIngredients. William Reed Business Media, England. Retrieved September 8, 2016.
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10. ^ "Supplement Marketers Will Relinquish $1.4 Million to Settle FTC Deceptive Advertising Charges". Federal Trade Commission. U.S. Federal Trade Commission. July 8, 2015. Retrieved January 1, 2019.
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15. Gutiérrez-Farfán I, Reyes-Legorreta C, Solís-Olguín M, Alatorre-Miguel E, Verduzco-Mendoza A, Durand-Rivera A (April 2021). "Evaluation of vinpocetine as a therapy in patients with sensorineural hearing loss: A phase II, open-label, single-center study". Journal of Pharmacological Sciences. 145 (4): 313–318. doi:10.1016/j.jphs.2021.01.010. PMID 33712282.
16. National Toxicology Program (September 2013). "Chemical Information Review Document for Vinpocetine (CAS No. 42971-09-5)" (PDF). U.S. Department of Health and Human Services. Retrieved December 28, 2018.
17. Office of the Commissioner (2019-06-03). "Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine". FDA. Retrieved 2019-06-04.
18. Hagiwara M, Endo T, Hidaka H (February 1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle". Biochemical Pharmacology. 33 (3): 453–457. doi:10.1016/0006-2952(84)90240-5. PMID 6322804.
19. Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon DS, et al. (May 2010). "Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism". Proceedings of the National Academy of Sciences of the United States of America. 107 (21): 9795–9800. doi:10.1073/pnas.0914414107. PMC 2906898. PMID 20448200.
20. Medina AE (June 2010). "Vinpocetine as a potent antiinflammatory agent". Proceedings of the National Academy of Sciences of the United States of America. 107 (22): 9921–9922. Bibcode:2010PNAS..107.9921M. doi:10.1073/pnas.1005138107. PMC 2890434. PMID 20495091.
21. Trejo F, Nekrassov V, Sitges M (August 2001). "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings". Brain Research. 909 (1–2): 59–67. doi:10.1016/S0006-8993(01)02621-X. PMID 11478921. S2CID 38990597.
22. French JM, King MD, McDougal OM (May 2016). "Quantitative Determination of Vinpocetine in Dietary Supplements". Natural Product Communications. 11 (5): 607–609. doi:10.1177/1934578X1601100512. PMC 5345962. PMID 27319129.
23. ^ McGrory K (July 9, 2015). "Tampa diet supplement firm pays $1.4 million settlement over 'brain power' pill claims". Tampa Bay Times. Retrieved January 1, 2019.
24. Hall H (September 18, 2012). "Procera AVH: A Pill to Restore Memory". Science Based Medicine. Retrieved January 1, 2019.
25. ^ Almada B (July 6, 2015). "False claims for brain supplement draw $152 million penalty from FTC". Orange County Register. Retrieved January 1, 2019.
26. ^ "Procera AVH Marketers Can Forget About Claiming to Reverse Memory Loss". National Law Review. July 30, 2015. Retrieved 1 January 2019.
27. ^ Myers S (July 8, 2015). "Memory Supplement Marketers Settle FTC Case for $150M". Natural Products Insider. Retrieved 1 January 2019.

• Nootropics
• PDE1 inhibitors
• Vasodilators
• Ethyl esters
• Vinca alkaloids