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Vinpocetine

Scientific Name(s): Vinca minor L.
Common Name(s): Apovincaminic acid, Cavinton, Creeping myrtle, Ethylapovincaminate, Kavinton, Small, common, dwarf, or lesser periwinkle, Vinpocetine

Clinical Overview

Use

Vinpocetine is used to enhance memory and increase brain metabolism. It has also been used for ischemia and reperfusion injury, and is considered a neuroprotective agent. However, there are few robust clinical studies to support the use of vinpocetine in stroke, dementia, or other diseases of the CNS.

Dosing

Most clinical studies have used between 5 and 30 mg vinpocetine given up to 3 times daily due to a short half-life (2 to 4 hours).

Contraindications

V. minor whole plant or extract is potentially contraindicated in constipation and hypotension.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Traditional uses for lesser periwinkle include antilactagogue and emmenagogue.

Interactions

Caution is warranted in patients on anticoagulant medications.

Adverse Reactions

Vinpocetine is well tolerated. Minor adverse reactions include facial flushing, dry mouth, drowsiness, headache, insomnia, anxiety, dizziness, nausea, and indigestion.

Toxicology

None well documented.

Botany

Vinpocetine is synthesized from the alkaloid vincamine, which is extracted from the leaves of the lesser periwinkle plant V. minor L. In the United States, the plant is commonly referred to as myrtle or creeping myrtle; however, this is misleading as myrtle normally refers to the true Myrtus species (Myrtaceae Family). The shrub is used as ground cover, and bears single, violet-purple flowers. The 2.5 cm long fruit contain numerous tiny seeds. The plant differs from its relative Vinca major by having smaller, leathery leaves with a hairless margin.Leung 2003, USDA 2014

History

Vinpocetine was first synthesized in the late 1960s from vincamine and has been sold under commercial names, such as Cavinton and Intelectol, since the late 1970s. Vinpocetine is primarily promoted for use in cerebral disorders of vascular origin, while V. minor has multiple purported, traditional uses including laxative, antilactaogogue, and emmenagogue.Duke 2003, Leung 2003

Chemistry

The plant contains many alkaloids, including vincamine and reserpine. Thus, biological activity of the semi-synthetic vinpocetine should not be confused with the whole plant. Chemical studies of vinpocetine are limited, except for those reporting its synthesis as ethyl-apovincaminate from the alkaloid vincamine. High-performance liquid chromatography determined apovincaminic acid as the primary metabolite of vinpocetine. It is soluble in ethanol, dimethyl sulfoxide, and acetone, and poorly soluble in water.Patyar 2011, Wan Ibrahim 2012, Xia 2010 See also vinca alkaloids in the Catharanthus roseus (Madagascar periwinkle) monograph.

Uses and Pharmacology

Vinpocetine exerts antioxidant effects. In animal models, vinpocetine inhibited the formation of reactive oxygen species and lipid peroxidation.Cai 2012, Cai 2013, Medina 2006, Nivison-Smith 2014, Sozański 2011, Zaki 2013, Zhuang 2013 Inhibition of calcium calmodulin-dependent phosphodiesterase type 1 has been demonstrated. Increases in cyclic adenosine 3′,5′-monophosphate (cAMP) may be responsible for benefits in cerebral circulation and decreased platelet aggregation. Additionally, the prevention of cAMP breakdown results in maintenance of the protein kinase and transcription factor cAMP-responsive, element-binding protein activation, possibly improving memory processing.Cai 2013, Medina 2006, Sozański 2011 Prevention of the upregulation of NF-kappaB and pro-inflammatory mediators by vinpocetine has been demonstrated.Medina 2010, Zhuang 2013

Audiology

Animal data

Vinpocetine 2 mg/kg was shown to prevent aminoglycoside-induced hearing loss in guinea pigs.Sitges 2004

Clinical data

Details of the study are limited, but vinpocetine prevented neurosensory hypoacusis in 118 tuberculosis patients (17 to 63 years of age) who had normal hearing or impaired hearing.Maliavina 2003 In 150 patients with chronic tinnitus, combination therapy of physiotherapy and vinpocetine (250 mL saline combined with 20 mg intravenous infusion or 20 mg oral therapy) once daily for 10 days improved the visual analog scale, with statistical benefit denoted as improvement by 2 or more points.Hahn 2008

Cerebrovascular disease (stroke/dementia)

Animal data

In animal experiments and models of hypoxia and ischemia, the vasoactive alkaloid vinpocetine has been shown to exert neuroprotective effects. Studies in rats and dogs have demonstrated increased blood flow and decreased resistance resulting in increased brain perfusion. Improved learning and memory has been shown in rats with dementia.Gulyás 2012, Herrera-Mundo 2013, Jincai 2013, Nyakas 2009, Zaki 2013

Clinical data

Studies from the 1970s and 1980s have been published, and vinpocetine is widely used in Russia and Hungary where many of the trials have been conducted. A pilot study (N = 30) reported improved scores in acute ischemic stroke, while a Russian study (N = 100) reported improvements in reversible vascular diseases including intermittent cerebral insufficiency.Deshmukh 2009 A large, multicenter study (N = 4,865) reported a reduction in patient complaints, severity of neurological symptoms, and improvements in Tinnetti scale scores and Mini Mental Status Exam scores.Chukanova 2010 A Cochrane systematic review of the effects of vinpocetine administered within 2 weeks in ischemic stroke found no evidence of benefit in reducing early (1 month) or late fatalities. In addition, the Cochrane review reported that vinpocetine 30 to 60 mg/day may be beneficial in dementia. However, few quality clinical trials were available for the review.Bereczki 2008, Deshmukh 2009, Szatmari 2003 A small randomized controlled trial conducted in 30 normotensive adults with a history of cerebrovascular disorders investigated the effects of vinpocetine with and without the cognitive enhancer, pyritniol, on blood viscosity and rheological modulation. After 2 weeks of treatment, administration of vinpocetine 10 mg/day led to significant (P<0.05) improvement in most, but not all, viscosity parameters (eg, serum fibrinogen, blood viscosity, erythrocyte rigidity index) and low shear whole blood viscosity (P<0.01). Meanwhile, the combination of both agents produced significant improvements in all 10 hemorheological parameters (P<0.05 for each; except for relative blood viscosity, low shear whole blood viscosity, and kinematic viscosity, which were P<0.01).Alkuraishy 2014 An uncontrolled pilot study in 30 adults with cerebral small vessel disease documented a significant improvement in vasodilatory effects in the right brain (P<0.05) after 3 months, but not 1 month, of vinpocetine 5 mg given 3 times daily. Improvements in the left brain were not statistically significant. Neurological and cognitive parameters also improved significantly compared to baseline as measured by the modified Rankin scale and mini-mental state examination, respectively (P<0.001 for each).Jovanovic 2013

Safety and efficacy of IV vinpocetine was investigated as an adjunct to usual comprehensive therapy in acute cerebral infarct patients in China in a randomized, open-label, controlled, multicenter trial (N=610; 469 vinpocetine, 141 control). Patients had magnetic resonance image-confirmed cerebral infarct with an onset between 48 hours and 14 days with subsequent neurological deficit but no intracranial hemorrhage. The addition of vinpocetine (30 mg IV once daily for 7 days) to usual therapy conferred significant improvements in daily activity scores 14 days after treatment (P<0.001) as well as cognitive (P=0.008), neurological function (P<0.001), and quality of life measurements (P=0.004) at the 90-day post-treatment assessment compared to patients who received usual therapy without vinpocetine. Transcranial Doppler confirmed improved cerebral blood flow in patients receiving vinpocetine compared to those who did not. Vinpocetine was well tolerated with only 2 mild adverse events associated with its use and both were mild: dizziness and diarrhea.Zhang 2016

Epilepsy

Animal data

Vinpocetine protected rodents and cats against induced convulsions.Dutov 1986, Nekrassov 2006, Nekrassov 2004, Sitges 2011 The mechanism of action may involve the blockade of presynaptic sodium and calcium channels. Brain gamma-aminobutyric acid and serotonergic mechanisms may also be involved.Dutov 1986, Sitges 2011, Sitges 2005

Clinical data

A Russian publication reports the effect of vinpocetine in epilepsy in a small study. In 20 of the 31 patients treated with vinpocetine, frequency of attacks decreased or completely disappeared; 7 patients showed no improvement and 4 patients experienced deterioration. Vinpocetine was most effective in generalized tonic-clonic convulsions.Dutov 1986 Another Russian study evaluated the effect of vinpocetine in newborns with hypoxic ischemic encephalopathy caused by intracranial birth trauma.Dutov 1991

Other uses

Vinpocetine inhibited proliferation of human breast cancer cells in vitro via cell cycle arrest and induction of apoptosis.Huang 2012

In a small clinical study, symptoms improved when vinpocetine was investigated in nonresponders to standard pharmacological therapy for urge incontinence and low-compliance bladder. Vinpocetine may also have a role in the treatment of urgency and interstitial cystitis.Truss 2000, Truss 2001 The therapeutic effect of vinpocetine on menopausal symptoms has been reported.Kiss 1990, Kolarov 2001

The efficacy of vinpocetine against several agents that cause gastric mucosal damage has been studied in rats.Nosálova 1993, Sümer 2011 Nociceptive properties have been studied in rodents.Abdel-Salam 2006, Knyihar-Csillik 2007

Animal studies suggest a role for vinpocetine in reducing the hyperactivity associated with fetal alcohol syndrome.Filgueiras 2010, Medina 2006, Nunes 2011

Dosing

Most clinical studies have used between 5 and 20 mg vinpocetine, given 3 times daily due to a short half-life (2 to 4 hours).Nie 2011, Ning 2011, Szatmari 2003

Due to poor aqueous solubility and a high first-pass effect, oral bioavailability is poor (7%), unless taken with food (increases upward of 60% have been suggested).Lohmann 1992, Sozański 2011 Citrate salt, sustained-release, and transdermal delivery forms have been evaluated.Hasa 2011, Mao 2013, Nie 2011, Ning 2011

Both vinpocetine and its active metabolite apovincaminic acid are absorbed from the GI tract. Vinpocetine appears to follow linear pharmacokinetics. It is metabolized exclusively in the liver, and widely distributed in the body systems including the CNS.Miskolczi 1990, Szakács 2001

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Traditional uses for lesser periwinkle include antilactagogue and emmenagogue.Duke 2003

Interactions

Limited studies from the 1990s showed an effect of vinpocetine on prothrombin time; however, clinically important interaction was not demonstrated.Akopov 1992, Feher 2009, Hitzenberger 1990 Caution is warranted in patients receiving blood-thinning agents.

Omeprazole does not influence the bioavailability of vinpocetine.Sozański 2011 Vinpocetine had no effect on the pharmacokinetics of imipramine, oxazepam, and glyburide.Patyar 2011

Adverse Reactions

Vinpocetine is well tolerated. Minor adverse reactions include facial flushing, dry mouth, drowsiness, headache, insomnia, anxiety, dizziness, nausea, and indigestion.Patyar 2011 A case report describes 1 possible case of agranulocytosis due to vinpocetine therapy.Kiss 1996 V. minor whole plant or extract is potentially contraindicated in constipation and hypotension.Duke 2003

Toxicology

Information regarding toxicity of lesser periwinkle whole plant or extract is limited. Hematological toxicity of vinpocetine has been reported in animals, and excess doses may result in hypotension.Duke 2003

References

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