Vinpocetine

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Vinpocetine

Common Names

  • Vinpocetine
  • Periwinkle
  • Vinca minor
  • Kavinton; Cavinton
  • Rgh-4405
  • Tcv-3B
  • Apovincaminic acid

For Patients & Caregivers

How It Works

Vinpocetine may be useful against some cerebrovascular disorders, but additional studies are needed. It has not been shown to treat or prevent cancer.

Vinpocetine is made from a compound found in the common periwinkle plant. It was developed in Europe as a drug but sold in the United States as a dietary supplement to improve brain function. Vinpocetine was shown to increase blood flow to the brain and has been studied as a treatment for Alzheimer’s disease and for disorders of the nervous and circulatory systems. However, more studies are needed before it can be recommended. Vinpocetine should not be confused with the chemotherapy drugs vincristine and vinblastine, which are also made from compounds of the periwinkle plant.

Purported Uses
  • Alzheimer’s disease
    Small studies have shown benefit with vinpocetine, but well-designed clinical trials are needed.
  • Cognitive decline
    Vinpocetine was useful in improving cognitive decline. More studies are needed.
  • Dementia
    A systematic review of studies did not find any effectiveness of vinpocetine for dementia.
  • Memory loss
    A few clinical trials have shown benefit. Large-scale studies are needed.
  • Stroke
    Some studies have shown benefits with vinpocetine in stroke patients, but larger studies are needed.
  • Cancer treatment
    Laboratory studies suggest some anticancer and increased radiation effects on tumor cells, but this has not been studied in humans.
Patient Warnings
  • A recent report from the National Toxicology Program of the National Institutes of Health suggests this supplement may cause harm to pregnant women or the fetus. In supplement labeling, vinpocetine may also be called periwinkle or vinca minor extract.
  • Patients with low blood pressure, a history of heart problems or strokes, or those on cardiovascular medications should consult their physician before using this product.
Do Not Take If
  • You are pregnant: A recent report from the National Toxicology Program of the National Institutes of Health suggests this supplement may cause harm to pregnant women or the fetus. In supplement labeling, vinpocetine may also be called periwinkle or vinca minor extract.
  • You are using blood-thinning drugs: Vinpocetine may increase their effects.
  • You are taking medication to lower high blood pressure: Vinpocetine may enhance their effects.
  • You are taking P-glycoprotein substrate drugs: Lab studies suggest that vinpocetine may alter the way these drugs work in the body. Clinical relevance is not yet known.
Side Effects
  • Flushing, rashes, gastrointestinal problems
  • Low blood pressure
  • Decreased white blood cell count

Case reports

  • Skin reaction, rapid heartbeat, stomach ache: In a man who took a supplement containing Ginkgo biloba and vinpocetine. However, it is uncertain whether both ingredients contributed equally to these reactions.
  • Low white blood cell counts: In a 73-year-old man after using vinpocetine for 50 days. His symptoms resolved after discontinuing vinpocetine.
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For Healthcare Professionals

Brand Name
Cavinton
Scientific Name
(14-ethoxycarbonyl-(3a,16a-ethyl)-14,15eburnamine), ethyl-apovincaminate
Clinical Summary

Vinpocetine is derived from vincamine, an alkaloid found in the common periwinkle plant. Originally developed in Europe where it is marketed as a drug called Cavinton, vinpocetine is sold in the United States as a dietary supplement to improve brain function.

Animal models suggest that vinpocetine has anti-inflammatory, antioxidant, antimitotic, anti-atherogenic, antithrombotic, and antiepileptic effects (1) (2) (3) (4) (5) (6) (7). Human studies show that vinpocetine enhances short-term memory (8), cognitive performance (9), and improves chronic cerebral dysfunction in elderly patients (10). It has also been studied as a potential treatment for Alzheimer’s disease (11), but a systematic review did not find benefit (12). Small studies suggest benefit with vinpocetine to maintain or improve hemorheologic parameters in patients with cerebrovascular disorders (13) (28), but a systematic review did not find enough evidence for benefit in patients with acute ischemic stroke (14). In a randomized open-label study, intravenous vinpocetine adjunctive to treatment for acute cerebral infarction improved cerebral blood flow, neurological functioning, and cognition (29).

Vinpocetine inhibits the growth of breast cancer cells in vitro and in vivo (15). In animal studies, it potentiates the effects of radiation therapy in tumor cells (16). However, vinpocetine has not yet been studied in humans for its potential anticancer effects.

Vinpocetine should not be confused with chemotherapy drugs such as vincristine or vinblastine, which are also alkaloids derived from the periwinkle plant.

Purported Uses
  • Alzheimer’s disease
  • Cognitive decline
  • Dementia
  • Memory loss
  • Stroke
  • Cancer treatment
Mechanism of Action

Vinpocetine is a synthetic ethyl ester of apovincamine derived from an alkaloid in the common periwinkle plant (17). In vitro, antioxidant and hydroxyl radical scavenging properties have been observed (18) (13). Vinpocetine inhibits phosphodiesterase 1 (PDE1) activity and improves cerebral blood flow by elevating cGMP and cAMP, increasing mitochondrial function, and improving glucose and oxygen utilization by the brain. Vinpocetine helps improve spatial memory in rats by preventing neuronal damage and favorably modulating cholinergic function (18). Antiepileptic effects were attributed to suppression of abnormal neuronal excitability via sodium channel regulation and dopamine release in striatal nerve endings (5) (6) (7). Vinpocetine antagonizes platelet-derived growth factor (PDGF)-induced extracellular matrix synthesis, suppresses intracellular reactive oxidative species (ROS) production, and inhibits extracellular signal-regulated kinase (ERK) 1/2 activation and vascular smooth muscle cell growth (4). Anti-atherogenic effects occur through inhibition of monocyte adhesion, oxidative stress, and inflammatory responses mediated by protein kinase B (Akt)/nuclear factor kappa B (NF-ĸB)-dependent pathways (3). Vinpocetine also demonstrates anti-inflammatory effects by inhibiting tumor necrosis factor-alpha (TNF-α)-induced NF-κB activities (19) as well as Akt and STAT3 activation (15). In a murine model of otitis media, vinpocetine suppressed S. pneumoniae-induced mucus production through mucin MUC5AC inhibition (27).

Administration of vinpocetine to chronic stroke patients increased glucose uptake and release in unaffected areas of the brain (12).

In vitro and in vivo studies indicate vinpocetine antitumor activity against human breast cancer cells occurs through G0/G1-phase cell cycle arrest and mitochondrial pathways of apoptosis (15). Vinpocetine can also increase the effects of radiation by increasing tumor oxygenation (16).

Warnings

A recent report from the National Toxicology Program of the National Institutes of Health suggests this supplement may cause harm to pregnant women or the fetus (30). In supplement labeling, vinpocetine may also be called periwinkle or vinca minor extract.

Contraindications

Patients with low blood pressure, a history of heart problems or strokes, or those on blood-thinning medications should consult their physician before using this product.

Adverse Reactions

Rare: Flushing, rashes, gastrointestinal problems (23), hypotension (24)

Case Reports

Fixed drug eruption, tachycardia, gastrointestinal pain: In a man who ingested a natural product containing Ginkgo biloba and vinpocetine (31). However, it is uncertain whether both ingredients contributed equally to these reactions.

Agranulocytosis: In a 73-year-old man after using vinpocetine for 50 days. His symptoms resolved after discontinuing vinpocetine (25).

Herb-Drug Interactions
  • Anticoagulants/antiplatelet agents: Vinpocetine may have additive effects and can increase risk of bleeding (13) (14) (26).
  • Antihypertensive agents: Vinpocetine may increase hypotensive effects (24).
  • P-glycoprotein substrates: In vitro studies indicate that vinpocetine strongly inhibits P-gp and may therefore alter the pharmacokinetics of substrate drugs (32). Clinical relevance has yet to be determined.
Herb Lab Interactions
  • May decrease red blood cell aggregation (13).
  • May reduce plasma and whole blood viscosity (13).
Dosage (OneMSK Only)
References
  1. Wang H, Zhang K, Zhao L, et al. Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury. Neurosci Lett. Apr 30 2014;566:247-251.
  2. Zaki HF, Abdelsalam RM. Vinpocetine protects liver against ischemia-reperfusion injury. Can J Physiol Pharmacol. Dec 2013;91(12):1064-1070.
  3. Zhuang J, Peng W, Li H, et al. Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-kappaB dependent mechanisms in apoE-/- mice. PLoS One. 2013;8(12):e82509.
  4. Cai Y, Knight WE, Guo S, et al. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration. J Pharmacol Exp Ther. Nov 2012;343(2):479-488.
  5. Sitges M, Chiu LM, Nekrassov V. Single and combined effects of carbamazepine and vinpocetine on depolarization-induced changes in Na+, Ca2+ and glutamate release in hippocampal isolated nerve endings. Neurochem Int. Jul 2006;49(1):55-61.
  6. Sitges M, Aldana BI, Chiu LM, et al. Characterization of phenytoin, carbamazepine, vinpocetine and clorgyline simultaneous effects on sodium channels and catecholamine metabolism in rat striatal nerve endings. Neurochem Res. Mar 2009;34(3):470-479.
  7. Trejo F, Nekrassov V, Sitges M. Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings. Brain Res. Aug 3 2001;909(1-2):59-67.
  8. Bhatti JZ, Hindmarch I. Vinpocetine effects on cognitive impairments produced by flunitrazepam. Int Clin Psychopharmacol. Oct 1987;2(4):325-331.
  9. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. Spring 1991;6(1):31-43.
  10. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc. May 1987;35(5):425-430.
  11. Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer’s disease. Am J Alzheimers Dis Other Demen. Mar-Apr 2006;21(2):113-118.
  12. Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive impairment and dementia. Cochrane Database Syst Rev. 2003(1):CD003119.
  13. Feher G, Koltai K, Kesmarky G, et al. Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases. Phytomedicine. Mar 2009;16(2-3):111-117.
  14. Bereczki D, Fekete I. Vinpocetine for acute ischaemic stroke. Cochrane Database Syst Rev. 2008(1):CD000480.
  15. Huang EW, Xue SJ, Zhang Z, et al. Vinpocetine inhibits breast cancer cells growth in vitro and in vivo. Apoptosis. Oct 2012;17(10):1120-1130.
  16. Amano M, Monzen H, Suzuki M, et al. Increase in tumor oxygenation and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride. J Radiat Res. Dec 2005;46(4):373-378.
  17. Feigin VL, Doronin BM, Popova TF, et al. Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial. Eur J Neurol. Jan 2001;8(1):81-85.
  18. Deshmukh R, Sharma V, Mehan S, et al. Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine — a PDE1 inhibitor. Eur J Pharmacol. Oct 12 2009;620(1-3):49-56.
  19. Jeon KI, Xu X, Aizawa T, et al. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci U S A. May 25 2010;107(21):9795-9800.
  20. Vlase L, Bodiu B, Leucuta SE. Pharmacokinetics and comparative bioavailability of two vinpocetine tablet formulations in healthy volunteers by using the metabolite apovincaminic acid as pharmacokinetic parameter. Arzneimittelforschung. 2005;55(11):664-668.
  21. Moghaddam AA, Aqil M, Ahmad FJ, et al. Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer’s disease. Drug Deliv. Apr 10 2014.
  22. Lin C, Chen F, Ye T, et al. A novel oral delivery system consisting in “drug-in cyclodextrin-in nanostructured lipid carriers” for poorly water-soluble drug: Vinpocetine. Int J Pharm. Apr 25 2014;465(1-2):90-96.
  23. Vinpocetine [monograph]. Altern Med Rev. Jun 2002;7(3):240-243.
  24. Imamoto T, Tanabe M, Shimamoto N, et al. Cerebral circulatory and cardiac effects of vinpocetine and its metabolite, apovincaminic acid, in anesthetized dogs. Arzneimittelforschung. 1984;34(2):161-169.
  25. Shimizu Y, Saitoh K, Nakayama M, et al. Agranulocytosis induced by vinpocetine. Medicine Online [serial online]. Accessed April 21, 2014.
  26. Kuzuya F. Effects of vinpocetine on platelet aggregability and erythrocyte deformability. Ther Hung. 1985;33(1):22-34.
  27. Lee JY, Komatsu K, Lee BC, et al. Vinpocetine Inhibits Streptococcus pneumoniae-Induced Upregulation of Mucin MUC5AC Expression via Induction of MKP-1 Phosphatase in the Pathogenesis of Otitis Media. J Immunol. 2015 Jun 15;194(12):5990-8
  28. Alkuraishy HM, Al-Gareeb AI, Albuhadilly AK. Vinpocetine and pyritinol: a new model for blood rheological modulation in cerebrovascular disorders-a randomized controlled clinical study. Biomed Res Int. 2014;2014:324307.
  29. Zhang W, Huang Y, Li Y, et al. Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial. Clin Drug Investig. Sep 2016;36(9):697-704.
  30. National Toxicology Program, National Institutes of Health. NTP Technical report on the prenatal developmental toxicity studies of vinpocetine. Accessed June 25, 2019.
  31. Cohen PR. Fixed Drug Eruption to Supplement Containing Ginkgo biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects. J Clin Aesthet Dermatol. Oct 2017;10(10):44-47.
  32. Manda VK, Avula B, Dale OR, et al. Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine. Medicines (Basel). Jun 5 2015;2(2):93-105.
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