Vinpocetine of Covex
for cognitive disorders

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Vinpocetine formula

Vinpocetine is a semi-synthetic derivative of vincamine, an alkaloid derived from the Vinca minor L. plant that has been used since the 1970s in Japan, Europe, Mexico, and Russia for the treatment of cerebrovascular and cognitive disorders. It can also be derived from tabersonine, the alkaloid extract of Voacanga seeds found mostly in West Africa.

COVEX, S.A.’s Vinpocetine is obtained following the method in its Spanish Patent: ES 549.105.

The starting material is Vincamine (derived from tabersonine, the alkaloid extract of Voacanga), manufactured at COVEX, S.A.’s own factory facilities in Colmenar Viejo (Madrid), Spain.

Vincamine (VC) is also an alkaloid of the eburnamenine type.

  • Nº CAS: 1617-90-9
  • Nº EC: 216-576-3
  • Molecular formula: C21H26N2O3
  • (CVX-DMF-100)

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Benefits of Vinpocetine

In the United States, it is commonly sold as a dietary supplement for the general population either alone or with other ingredients. Its numerous proposed uses include for improvement of brain function, rapid weight/fat loss, increases in energy, enhancement in focus and visual acuity, prevention of motion sickness, hearing and eye disorders, chronic fatigue syndrome and treatment of menopausal symptoms. Some of these purposes make it a product for athletes too. (Chemical Information Review Document for Vinpocetine, National Toxicology Program, U.S. Department of Health and Human Services, Research Triangle Park, NC, 2013).

According to the Physicians' Desk Reference for Nutritional Supplements, doses may range from 5-20 mg/day.

Chemical identification and analysis of Vinpocetine

  • Generic Name (D.C.I.): Vinpocetine
  • Chemical Name: Eburnamenine (3α,16α)-14- carboxylic acid ethyl ester. Ethyl apovincaminate
  • CAS RN: 42971-09-5
  • Laboratory code: DMF-400

Similar standards for the identity and quality of vinpocetine products have been specified by the United States, British, and European Pharmacopoeias.

Vinpocetine specifications

[42971-09-5] NW
Eburnamenine-14-carboxylic acid, ethyl ester, (3α,16α)-; Ethyl apovincamin-22-oate.
Appearance: White or slightly yellow, crystalline powder.
Solubility: Practically insoluble in water, soluble in methylene chloride, slightly soluble in anhydrous ethanol.
A. Specific optical rotation: +127.0° to +134.0° (dried substance).
B. Infrared absorption spectrophotometry. According to Vinpocetine CRS.
C. HPLC The retention time of the main peak of the Sample solution corresponds to that of the principal peak for the Stock standard solution, as obtained in the test for Organic Impurities.
RELATED COMPOUNDS, (HPLC) A) Ethyl vincaminate: Not more than 0.6%.
B) Apovincamine: Not more than 0.5%.
C) Methoxyvinpocetine: Not more than 0.3%.
D) Dihydrovinpocetine: Not more than 0.5%.
Unspecified impurities, each one:
Not more than 0.10%.
Total impurities: not more than 1.0%.
LOSS ON DRYING Not more than 0.5% of its weight.
SULPHATED ASH (Residue on ignition) Not more than 0.1%.
HEAVY METALS Not more than 10 ppm.
ACIDIMETRIC ASSAY (Titrimetry) Not less than 98.5% and not more than 101.5% of C22H26N2O2, calculated on the dried basis.
RESIDUAL SOLVENTS Ethanol ≤ 2000 ppm. (0.20%).
Methylene chloride ≤ 100 ppm. (0.01%).
TAMC ≤ 103 CFU / 1 g.
TYMC ≤ 102 CFU / 1 g.
Gram-bile tol. ≤ 10 CFU / 1 g.
Escherichilla coli Absence / 1 g.
St. Aureus Absence / 1 g.
Ps. Aeruginosa Absence / 1 g.
Salmonella Absence / 10 g.
PYROGENS Apyrogens

Clinical trial safety and efficacy information

This information has been divided into three groups: the standard controlled studies with placebo, the controlled studies with a reference therapy, and non-controlled studies.

Several placebo controlled studies are presented. They were performed in Germany, England, Italy, Hungary and Russia and have resulted in publications in peer-reviewed literature. Subjects could be healthy volunteers (without treatment or subjected to hypoxia) or patients with cerebral vascular disorders, low level of vestibular stability, central nervous system (CNS) degenerative disorders, mild to moderate OPS (Organic Psycho-syndrome), ischemia or senile dementia of vascular origin. Treatment doses, schedules and routes were varied and could be from 10 mg/day to as high as 120 mg/day administered p.o. in most cases during up to two years of treatment. Age groups were also very varied, with some studies concentrating on younger patients, patients of no specific age group, and most on older subjects. As was the case for pharmacokinetics, children are absent from the trials since the drug is not intended for them. Sex ratios were adequate. Each of the clinical trials was correctly conducted as can be seen from the publications, with scientifically valid preparation and monitoring. Placebo was always given with the same regimen as the drug, and in a way as to make it indistinct. A very wide range of parameters were studied: from the least scientific subjective evaluation to more sophisticated neurological and psychological evaluation tools such as the Clinical Global Impressions (CGI), “Sandoz clinical assessment geriatric” (SCAG) scale and Line Analogue Rating scales (LARS), as well as side and other effects.

The authors have also presented also data from several controlled trials with reference therapies to better establish the usefulness of their pharmaceutical products. The trials were conducted in Japan and Hungary, and meet international standards for such trials. Vinpocetine was compared with Ifenprodil tartrate (known for its cerebral vasodilator effect), DHEM (Dihydroergotoxine mesylate), Xantinol nicotinate (known for its vasodilatory effect in the ear), and Lucidril (also a vasodilator). A study attempting to identify the best dose for vinpocetine is also presented in this section. As in the previous section, groups were of adequate size, sex ratio and age distribution. The patients suffered from a variety of disorders: cerebral infarction, cerebral arteriosclerosis, ischemia, and different types of deafness. The authors examine the effect of vinpocetine in terms of neurological parameters, metabolic and circulatory indicators, and patients’ hearing impairment symptoms.

The last part of the studies, the non-controlled studies, contains some different clinical trials (in Russia, Japan, Portugal, etc.). The most impressive of these trials is the Portuguese trial which examined 8.940 patients suffering from a wide range of cerebrovascular disorders. The other trials were carried out on groups of 30-288 patients, male or female, of different ages. Posology was p.o. one or three times daily (except for two of the Russian studies, which used the i.v. route) with doses of 10-30 mg/day. Patients suffered from various cerebrovascular diseases, chronic ischemia and epilepsy. Clinical symptoms were examined, with SCAG scale, cerebral blood flow, neurological and symptomatological indicators.

On the whole, all these studies can be considered as valid clinical trials, as demonstrated by their publication in peer-reviewed international scientific journals. Observations and conclusions can now be drawn in the following sections.


As compared with placebo, Vinpocetine was found to be capable of reducing hypoxia through oxygenation in healthy men that were submitted to induced hypoxia with a lower than normal concentration of oxygen (10.5 %). The volunteers reported better subjective well-being in the treated vs. Placebo group. Vinpocetine was also capable of improving memory retention time processes in middle-aged (25-40) healthy women. This result was confirmed by another study on a different group of women of similar age. In patients with a low level of vestibular stability, vinpocetine was shown to be able to prevent antimotion. In Italian patients with CNS degenerative disorders or chronic cerebral dysfunctions of vascular origin, the authors observed an improvement in all the parameters used to measure the efficacy of the treatment. In the first study, 73-77 % of patients showed an improvement in terms of the severity of illness, and in the second, approximately 56 % reflected a similar improvement. In both cases, this is significantly better than with placebo. Hindmarch et al. in England and Blaha et al. in Germany have both studied the effect of vinpocetine on organic psychosyndrome with doses of up to 60 mg/day or placebo. A dose related effect was seen between doses of 15 mg/day or 60 mg/day. A significant improvement was seen in both trials, with up to 80 % of patients showing improvements. This was significantly better than with placebo. The last of this group of trials was on patients with chronic degenerative cerebrovascular function and they also showed marked improvement beyond the placebo effect.

Some of the trials studying the effects of vinpocetine as compared with reference therapies have yielded the following results. Vinpocetine is markedly better than Ifenprodil tartrate or DHEM for the treatment of sequels of cerebral infarction, cerebral arteriosclerosis and transient ischemia attacks. The parameter used is a subjective index of the physician´s impression. However, there seems to be little evidence of bias and at the very least, the efficacy of vinpocetine in these diseases is clearly established. Vinpocetine also proved more efficacious than Xantinol nicotinate in cerebrovascular patients. An improvement of the condition was observed in 60.6 % of cases, significantly better than the 47.1 % attained by Xantinol nicotinate alone. However, the patients were at a near-terminal stage and in fact a large proportion of patients died during the treatment, which makes assessment difficult. In the last trial, vinpocetine proved as useful as Lucidril in the treatment of auditive disorders of vascular origin, but did not improve on it.

The last set of clinical trials is the set of non-controlled, open studies. As stated before, the most impressive is the Portuguese study with more than 8.000 patients included. This study concludes that an improvement in the condition was observed in approximately 76 % of assessable cases in patients with a wide variety of vascular disorders. Inconclusive cases were low, at less than 25 %, considering the size and scope of the study.

The other open study showed that vinpocetine can significantly improve the condition of patients with cerebrovascular disorders, such as cerebral apoplectic sequela or transient ischaemic attack in up to 77 % of cases.

In the case of cerebral arteriosclerosis, and chronic cerebral insufficiency, the therapy was also effective as judged by psychological tests and circulatory parameters.

The conclusion regarding the efficacy of VINPOCETINE is that it can be useful in the treatment of the following diseases:

  • Symptoms of cerebrovascular disorders such as memory loss, aphasia, apraxia, motion sickness, vertigo, headache, and vasovegetative symptoms associated with menopause; other cerebral affectations such as cerebrovascular insufficiency, or ischaemic lesions;
  • Certain eye diseases;
  • Hearing impairment due to circulatory disorders.


An exhaustive list of all the different side-effects observed in all these trials would be redundant. In most of the trials, no side-effects were observed. However, in some trials, especially in those with older patients, some small disturbances were reported.

In the studies with placebo, the following side effects were reported in five cases: face-flushing, dyspepsia, dry mouth, palpitations, vertigo, and more minor disturbances. In all cases, these side effects were not distinguishable from those caused by the placebo studies. All of the authors conclude that vinpocetine has no clinically relevant side-effect.

In trials dealing with patients treated with Vinpocetine or a reference substance, no more side-effects have surfaced. Adverse reactions were at a very low frequency (always less than 5 % of total) and the symptoms were trivial (epigastric pain, hot flashes). In the trial involving Xantinol nicotinate, 15.1 % of the vinpocetine patients died during treatment. This was not due to a toxic effect of the drug and in fact, some 30.6 % of the reference therapy group also died during the study. This drug is known not to be toxic and the deaths were due to the near-terminal stage of the patients at the start of the trials.

In the open non-controlled studies no side effects were reported in the smaller trials except for the one by Ebi where slightly more than 2 % of patients exhibited adverse reactions. One discontinued treatment due to a mild allergic reaction. An in-depth study of side effects was carried out by Diogo on the 500 cases of reported adverse reaction (5.59 % of total). The most important reactions reported are hypotension and tachycardia. The frequencies of these affectations are not distinguishable from those obtained in the previous placebo studies.

From these very thorough studies of side effects in several thousand patients, it can be safely concluded that vinpocetine has virtually no side effect. In the technical file and the leaflet the different observed side-effects are included. None were left out and it can even be said that those included are superfluous, as data shows that this is no more than placebo effect.

An interaction with hypotensive drugs is not discarded. Furthermore, no evidence of interactions has surfaced in more than 10 years of marketing in other countries so it can safely be said that Vinpocetine has no interactions. Contraindications for pregnancy arise from animal studies and have been discussed in the relevant section.

From the series of clinical trials, it can be concluded that it is satisfyingly demonstrated that the indications for Vinpocetine are accurate and based on solid medical evidence. In the same way, it can be said that the proposed contraindications and warning of possible side-effects cover all the known aspects of Vinpocetine.

Interactions with other drugs

As Vinpocetine was shown to exert a potential hypotensive effect, an experiment has been included which investigated the possible interactions between the drug and known hypotensors. A large group of patients aged between 55-75 years old suffering from mild to severe hypertension were treated for 6 weeks with hypotensive drugs (Visken™ and Hypothiazide™) and then 6 weeks with vinpocetine at 20 mg/day. In the of examinations haemogram, urine liver function, total lipid level, serum cholesterol, plasma Na- and K concentrations, urea nitrogen and serum creatinine values and ECG were controlled. During the observation period of several months clinical sign which could be attributed to an interaction between Vinpocetine and hypotensive drugs combination treatment could not be observed. In fact the authors conclude the study by recommending the combination of Vinpocetine and hypotensives.

Another study was performed to investigate of Vinpocetine (VP) with a cardiotonic drug for a 3-4 week treatment with up to 60 mg/day of VP. Although the purpose of this study is to investigate the possibility of complementary or synergistic aspects of the two drugs in patients suffering from chronic cerebral insufficiency or arteriosclerosis, it is a useful study from the point of view of interactions. In the subjects treated with vinpocetine, no negative interactions were observed with the cardiotonic drugs. The authors even consider that the combined therapy optimises the effect as compared with the single drug.

It can be concluded, therefore, are no proven interactions with known drugs, in particular hypotensors or cardiotonics. Nevertheless, a precautionary measure, a warning is included in the form of a statement which indicates that such interactions are not ruled out and that such combinations should be properly supervised.

In any case, Heparin should not be used together with vinpocetine.

Clinical trials were carried out to determine the efficacy of Vinpocetine in the treatment of neurological signs and symptoms as well as cognitive dysfunction in patients with cerebrovascular insufficiency and with primary degenerative dementia. The studies show that vinpocetine has beneficial results in the global improvement of the neurological conditions and in many functions of memory and learning. Vinpocetine has been demonstrated to be an effective drug in the treatment of geriatric diseases of vascular or degenerative neurological disorders. Good drug tolerance has been shown and adverse reactions are minimal.

Bibliography of Clinical trial safety and efficacy information

0640. Blaha L., Erzigkeit H., Adamczyk A. Clinical evidence of the effectiveness of vinpocetine in the treatment of organic psychosyndrome. Human Psychopharmacology, 4: 103-111 (1989).

0655. 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., 35: 425-430 (1987).

1031. Kahán, Á., Oláh, M. Use of Ethyl Apovincaminate in Ophthalmology Therapy. Arzneim.-Forsch., 26, 10a (1976).

1032. Brooser G., Anda, L., Domán, J. Preliminary Report on the Use of Ethyl Apovincaminate in Affections of the Eyeground. Arzneim.-Forsch., 26, 10a (1976).

1035. Vamosi B., Molnár L., L. Demeter J., Tory F. Comparative Study of the Effect of Ethyl Apovincaminate and Xantinol Nicotinate in Cerebrovascular Diseases. Immediate drug effects on the concentrations of carbohydrate metabolites and electrolytes in blood and CSF. Arzneim.-Forsch., 26, 10a: 1980-1984 (1976).

1057. Hitzenberger, G., Sommer W., Grandt R., Influence of Vinpocetine on Warfarin-Induced Inhibition of Coagulation. Intl. J. Clin. Pharmacol., Therapy and Toxicol., 28, 8: 323-328 (1990).

1058. Hitzenberger, G., Schmid R., Braun W., Grandt R., Vinpocetine Therapy does not Change Imipramine Pharmacokinetics in Man. Intl. J. Clin. Pharmacol, Therapy Toxicol., 28, 3: 99-104 (1990).

1099. Bodo D., Kotovskaya A.R., Galle R.R., et al. Effectiveness of Cavinton as an Antimotion Drug. Kosm. Biol. Aviokosm. Med., 16 (3): 49-51 (1982).

1116. Schaffler K. Placebo-Controlled, Double-Blind Crossover Study to Investigate the Hypoxia-Protective Effect of Vinpocetine by Psychophysiological Methodology in Healthy Volunteers. Drug Development Research 14: 247-250 (1988).

1131. Lohmann, A. et al. Bioavailability of Vinpocetine and Interference of the Time of Application with Food Intake. Arzneim.-Forsch., 42 (II), 7 (1992).

1144. Lohmann, A., Grobara, P., Dingler, E., Investigation of the Possible Influence of the Absorption of Vinpocetine with Concomitant Application of Magnesium-Aluminium-Hydroxide Gel. Arzneim.-Forsch., 41 (II), 11 (1991).

1172. Subhan Z., Hindmarch I. Psychopharmacological Effects of Vinpocetine in Normal Healthy Volunteers. Eur. J. Clin. Pharmacol., 28: 567-571 (1985).

1202. Ishchenko, M. M., Dorogiy A. N., Nechay S. I., Shkrobot S. I., Vasoactive and Cardiotonic Drugs in the Treatment of Initial Manifestations of Cerebrovascular in Occlusive Diseases of Major Blood Vessels of the Head. Zh. Nevropatol. Psikhiatr., 91, 1: 71-75 (1991).

1203. Mints A.Ia., Litvinenko A.A., Bachinskaya N.Yu. Cerebral Circulation and Various Indices of the Functional Status of the Brain during Ageing. Zh. Nevropatol Psikhiatr., 85, 9: 1374-1378 (1985).

1206. Dutov A.A., Tolpyshev B.A., Petrov A.P. et al. Use of Cavinton in Epilepsy. Zh. Neuropatol. Psikhiatr., 86 (6): 850-855 (1986).

1208. Ishchenko, M. M., Shkrobot S. I., Borak V. T., Effect of Cavinton and Sulfocamphocain on Systemic and Cerebral Hemodynamics in Patients with Early Forms of Cerebrovascular Diseases. Zh. Nevropatol. Psikhiatr.,87, 8: 1160-1164 (1987).

1210. Ishchenko, M. M., Dorogiy A. N., Nechay S. I., Shkrobot S. I., Clinico-Hemodynamic Evaluation of the Efficacy of Vasoactive and Cardiotonic agents in the Combined Treatment of Arteriosclerosis Patients with Chronic Cerebral Circulatory Insufficiency. Zh. Nevropatol. Psikhiatr., 87, 9: 1313-1320 (1987).

1212. Burtsev E.M., Tugutov A.I. Therapeutic Effect of Cavinton in Chronic Cerebral Circulatory Insufficiency. Zh. Nevropatol. Phikhiatr., 85, 1: 53-56 (1985).

1215. Ischenko, M. M. Dorogiy A. N., Nechay S. I., Shkrobot S. I., Vasoactive and Cardiotonic Chemotherapy for Transient Disorders of Cerebral Circulation Due to Occlusions of Major Vessels of the Head. Klin. Med. Mosk.,69, 7: 82-86 (1991).

1227. Bondarenko, I. P., Correction of Hemodynamics and Metabolic Disorders in Patients with Ischemic Heart Disease. Vrach. Delo, 3: 31-34 (1988).

1228. Taiji H., Kanzaki J. Clinical Study of Vinpocetine in the Treatment of Vertigo. JPN Pharmacol., 14, 2: 577-589 (1986).

1249. Farsang C.S., Kertész G., Bánki M.C., et al. Effect of Two Years’ Cavinton Treatment on the ECG. Therapia Hungarica, 35, 3: 125-128 (1987).

1256. Kovács G. Observations with Cavinton Treatment in Acute Cerebral Ischaemic Conditions. Therapia Hungarica, 32, 4: 155-157 (1984).

1257. Gálos, G., Examinations of Interactions in the Course of the Simultaneous Use of Cavinton, Saluretic and Beta-Receptor Blocker with Special Regard to Blood Pressure. Therapia Hungarica, 32, 4: 169-170 (1984).

1265. Ebi O. Open-labelled Phase III Clinical Trials with Vinpocetine in Japan. Hung., 33, 1: 41-49 (1985).

1295. Nikolaev, M.P., Konstantinova, Z.D., Mertsalova, O.N., at al. Prospects of Using Cavinton in Méniere´s Disease. Vestn. Otorinolaringol., 42 (3): 18-22 (1980).

1314. Peruzza M., DeJacobis M. A Double-Blind Placebo Controlled Evaluation of the Efficacy and Safety of Vinpocetine in the Treatment of Patients with Chronic Vascular or Degenerative Senile Cerebral Dysfunction. Advances in Therapy, Vol. 3, No. 4, July/August: 201-4 (1986).

1322. Ördögh, B., Sárossy, D., Klimstein, G. Therapeutic Action in Hearing Defects of Neurological Origin. Therapia Hungarica, 26 (1): 16-19 (1978).

1323. Jasper A. Effectivity of Cavinton and Lucidril in the Treatment of Hearing Defects of Different Origin. Therapia Hungarica, 27(1): 29-31 (1979).

1349. Tamaki Norihiko, Kusunoki Tadaki, Matsumoto Satoshi. The Effect of Vinpocetine on Cerebral Blood Flow in Patients with Cerebrovascular Disorders. Advances in Therapy, 2 (2): 53-59 (1985).

1350. Grandt, R., Braun W., Schulz H.-U., Frercks H.-J., Glibenclamide Steady State Plasma Levels during Concomitant Vinpocetine Administration in Type II Diabetic Patients. Arzneim.-Forsch., 39 (II), 11 (1989).

1356. Boda, J., Karsay K., Czako L., Fugi S., Kovacs I., Maczko P.A., Examination of Cavinton Effect in Elderly Diabetic Patients. Therapia Hungarica, 37, 3: 176-180 (1989).

1357. Kiss, E. Adjuvant Effect of Cavinton in the Treatment of Climacteric Symptoms. Therapia Hungarica, 38 (4): 170-173 (1990).

1358. Alberth B., Somogyi E. Observations with Cavinton (RGH-4405), Therapia Hungarica, 27, 1: 17-27 (1979).

1359. Hindmarch I., Fuchs H., Erzigkeit H. Efficacy and Tolerance of Vinpocetine in Ambulant Patients Suffering from Mild to Moderate Organic Psychosyndromes. International Clinical Psychopharmacology, 6: 31-43 (1991).

1360. Bhatti J. Z., Hindmarch I. Vinpocetine Effects on Cognitive Impairments Produced by Flunitrazepam. Inter. Clin. Psychopharmacology, 2: 325-331 (1987).

1366. Manconi E., Binaghi F., Pitzus F. A Double-Blind Clinical Trial of Vinpocetine in the Treatment of Cerebral Insufficiency of Vascular and Degenerative Origin. Current Therapeutic Research, Clin. Exp., 40, 4: 702-709 (1986).

1367. Otomo E., Atarashi J., Araki G., et al. Comparison of Vinpocetine with Ifenprodil Tartrate and Dihydroergotoxine Mesylate Treatment and Results of Long-Term Treatment with Vinpocetine. Current Therapeutic Research Clin. Exp., 37, 5: 811-821 (1985).

1383. Hadjiev D., Yancheva S. Rheoencephalographic and Psychological Studies with Ethyl Apovincaminate in Cerebral Vascular Insufficiency. Arzneim.-Forsch., 26, 10a. 1947-1950 (1976).

1506. Diogo N., Antunes, J.E. Multicenter clinical trials regarding effect of Vinpocetine on cerebral vascular disorders. Momento Medico, Vol. 30 (6): 25-31 (1990).

2769. Vas Ádam, Gulyás Balazs, Eburnamenine Derivatives and the Brain, Medical Research Rewiews, Vol 25, Nº 6, 737-757 (2005).

2916. Valikovics A., Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions, Ideggyogy Sz., 60 (7–8) 301–310 (2007).

3519. Wollschlaeger B., Efficacy of Vinpocetine in the Management of Cognitive Impairment and Memory Loss, JANA, Vol. 4, No. 2, 25-30 (2001).

3654. Chemical Information Review Document for Vinpocetine, National Toxicology Program, U.S. Department of Health and Human Services, Research Triangle Park, NC, (2013).



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