Focus on Vinpocetine

J. Maslarova, R. Nikolov

Chemical Pharmaceutical Research Institute,

Sofia, Bulgaria



Ethyl apovincaminate (Vinpocetine) is a vincamine derivative has been used in the clinical practice for over 25 years for the treatment of cerebrovascular disorders and related symptoms. The effects of vinpocetine on cerebral blood flow, brain metabolism, memory functions, and its neuroprotective action have been confirmed in the past years in numerous animal experiments and human studies.
The aim of the present paper is to review the preclinical and clinical studies on vinpocetine.

Pharmacological properties

Vinpocetine exerts a brain neuroprotective effect by a combined action on cerebral circulation, brain metabolism, and rheological properties of the blood. Kiss and Karpati (1996) summarized the pharmacological studies on vinpocetine. Early experiments showed an improvement of the cerebral circulation and oxygen utilization without changes in systemic circulation, cerebral protection in conditions of hypoxia/ischaemia, cognition-enhancing and anticonvulsant activity, and improvement of rheological properties of the blood. Later studies confirmed the above effects and clearly demonstrated a direct neuroprotective action at a cellular level.

Cerebral circulation

· Increases brain perfusion by improvement of cerebral blood flow and decrease of the cerebral vascular resistance in dogs. (Karpati and Szporny, 1976; Szmolenszky and TÖrÖk, 1976);
· Increases the cerebral capillary flow rate in dogs (Szmolenszky and TÖrÖk, 1976)
· Improves total cerebral blood flow in normal conditions and in hypoxic hypoxia in dogs (Bencsáth et al., 1976).

Brain metabolism

· Enhances the cerebral metabolic rate of oxygen in dogs (Karpati and Szporny, 1976);
· Prevents the local cerebral glucose utilization increase, caused by forebrain ischaemia of 10-min duration in rats (Rischke and Krieglstein, 1990).

Neuroprotective action in conditions of hypoxia/ischaemia

· Increases latency to ischemic convulsion in a dose-related manner In a rat model of cerebral ischaemia (bilateral carotid artery occlusion). After 5 days administration (25 mg/kg/day) increases survival time (King and Narcavage, 1986).
· Demonstrates a pronounced protective effect against hypoxia and ischaemia in several animal models (Lamar et al., 1988).
· Increases the local CBF in a model of rat forebrain ischaemia of 10-min duration after 1 h of recirculation (Rischke and Krieglstein, 1991), and at the 7th day after the ischaemia (Rischke and Krieglstein, 1990).
· Increases the neuroprotective effect of adenosine in a model of cytotoxic hypoxia in cultured chick embryo neurons (Krieglstein and Rischke, 1991).
· Reduces the hippocampal neuronal necrosis after pre- or post-ischemic administration in a model of forebrain ischaemia in rats (Rischke and Krieglstein, 1991).
· Exerts a pronounced brain protective effect in doses 5, 10 and 20 mg/kg i.p. in different experimental models of hypoxia/ischaemia (Maslarova and Nikolov, 1999). The effect was similar to nicergoline and weaker than the effect of piracetam.

Biochemical mechanisms

· Vinpocetine showed weaker calcium antagonistic properties in comparison with the effects of flunarizine, verapamil, diltiazem and nimodipine in isolated rabbit basilar and splenic artery (Lamar et al., 1988).
· In binding experiments on rat brain cortical membranes vinpocetine showed properties of a quisqualate/AMPA antagonist of some specificity and selectivity (Kiss et al., 1991).
· Using primary cultures of rat cerebral cortex Lakics et al. (1995) showed that the blockade of voltage-gated sodium channels is a possible mechanism of action for the neuroprotective and anticonvulsant properties of vinpocetine.
· Antioxidant and ROS (reactive oxygen species) scavenging action in conditions in which ROS are excessively generated such as oxidative stress, hypoxia/reoxygenation, ischaemia/reperfusion (Stolc, 1999).
· In vitro studies demonstrated the effect of vinpocetine on Ca2+-calmodulin dependent cGMP-PDE, voltage-operated Ca2+ channels, glutamate receptors and voltage-dependent neuronal Na+ channels (Bonoczk et al., 2000).

Other effects

· Increases myocardial and renal capillary flow rate in dogs (Szmolenszky and TÖrÖk, 1976).
· Anticonvulsive effect in electroshock and pentylenetetrazole-induced convulsions in mice (Palosi and Szporny, 1976)
· Cognition-enhancing activity in models of scopolamine-induced and hypoxia-induced memory impairment in rats (DeNoble et al., 1986)

Clinical efficacy

Cerebrovascular disease

Szobor and Klein (1976) studied the effectiveness of vinpocetine in 100 patients with neurovascular diseases distributed in two groups. Forty six patients were given combined treatment (i.m. and oral) vinpocetine in daily dose 10-30 mg; 54 patients were treated with oral vinpocetine 30-45 mg daily. Vinpocetine caused significant improvement in the reversible vascular diseases such as hypertensive encephalopathy, intermittent vascular cerebral insufficiency and cerebral arteriosclerosis.
Solti et al. (1976) demonstrated in 10 patients with cerebrovascular diseases that vinpocetine (10 mg i.v. drop infusion within 4-6 min) reduced cerebral vascular resistance and increased cerebral fraction of cardiac output without effect on systemic circulation.
Hajiev and Yancheva (1976) studied the effect of vinpocetine on the rheoencephalogram in 50 patients with ischemic disturbances of cerebral circulation. The drug was administered in a single i.v. dose of 10 mg and orally three times daily 5 mg for a month. Vinpocetine caused an increase of cerebral circulation demonstrated by an improvement of the rheoencephalographic parameters, especially tga 1 (tangent of the angle of inclination of slow systolic filling), which reflected changes in the small blood vessels. Blood flow increased most markedly in the gray matter.

Orosz et al., (1976) studied the effect of vinpocetine after i.v. administration on cerebral circulation in neurosurgical patients by use of H2 clearance technique and serial carotid angiography. Vinpocetine improved the cerebral circulation, particularly in patients with damaged cerebral vascularisation.
Vinpocetine was found to increase the cerebral blood flow in the ischaemia affected area of patients with cerebrovascular disease (Tamaki et al., 1985).

Burtsev et al. (1992) summarized 10-years experience of the use of vinpocetine in 967 patients with different cerebrovascular diseases. Better effect was found in patients with early forms and primarily chronic forms: neurocirculatory dystonia, initial manifestation of cerebral blood flow insufficiency, circulatory encephalopathy. In ischemic stroke the improvement of cerebral symptoms was more rapid in the patients with normal blood pressure.

Using Doppler ultrasonic technique Miyazaki (1995) examined the changes in the cerebral vascular resistance after 2-months administration of vinpocetine in patients with cerebral circulatory disease. Continuous index and pulsatility index in the internal carotid artery were used as parameters for monitoring the changes in the cerebral vascular resistance. Vinpocetine caused a significant increase of the continuous index and a decrease of the pulsatility index, changes indicating cerebral vascular resistance decrease.
Szakall et al., (1998) studied the effect of vinpocetine on the cerebral glucose metabolism of chronic stroke patients by the use of positron emission tomography. Single-dose of intravenous vinpocetine improved significantly the transport of glucose through the blood-brain barrier in the whole brain, the entire contralateral hemisphere, and in the brain tissue around the infarct area of the affected hemisphere.
Gulyas et al. (2001) studied the effect of a single-dose i.v. infusion of vinpocetine on the cerebral blood flow (CBF) and glucose metabolism of post-stroke patients. Regional and global cerebral metabolic rates of glucose, transcranial Doppler and single photon emission tomography measurements were performed. Although the single-dose of vinpocetine did not affect significantly the regional or global metabolic rates of glucose, the glucose transport was significantly improved in the whole brain, in the contralateral hemisphere and in the peri-infarct area of the affected hemisphere. A slightly increased cerebral blood flow was observed in the contralateral hemisphere and a decreased flow was found in the affected hemisphere.

Feigin et al. (2001) studied the efficacy and safety of vinpocetine in acute ischemic stroke. Thirty patients with computed tomography verified diagnoses were enrolled in this pilot study. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. The results showed that the National Institute of Health Stroke Scale score was marginally significantly better in the vinpocetine treated group at the end of the 3 months follow-up period.

Rheological properties of the blood

Hayakawa (1992) studied the effect of vinpocetine on the deformability of erythrocytes in patients with chronic ischemic cerebrovascular disease. Vinpocetine led to a significant improvement of the red blood cell deformability after 3 months administration.
Akopov and Gabrielian (1992) studied the effect of vinpocetine in comparison with the aspirin, nifedipine, and dipyridamole on platelet aggregability in patients with atherosclerosis. The drugs studied reduced platelet aggregability when aggregation was induced by ADP, adrenaline, or collagen.
Inhibits platelet aggregation and adhesion in patients with cerebrovascular disorders (Itoh, 1982),

Memory functions

Using the psychological tests "10 words" and Wechsler's fifth subtest Hajiev and Yancheva (1976) investigated the effect of vinpocetine (one month oral administration) on memorizing capacity of 50 patients with ischemic disturbances of cerebral circulation. Vinpocetine improved considerably the memory functions in most of the patients.

Szobor and Klein (1976) have found that vinpocetine (30-40 mg daily) improved memory functions and attention in 46 out of 60 patients with neurovascular diseases, using psychodiagnostic tests (free association, figural Bourdon, Ranschburg-Ziechen test).
Balestreri et al. (1987) studied the effect of vinpocetine in a double blind clinical trial on 42 elderly patients with chronic cerebral dysfunction. The patients received 10 mg vinpocetine three times daily for 30 days then 5 mg for 60 days. Vinpocetine caused improvement of the memory functions of the patients as measured by the Clinical Global Impression scale, the Sandoz Clinical Assessment-Geratric scale and the Mini-Mental Status Questionnaire.
Bhatti and Hindmarch (1987) studied the effect of pre-treatment with vinpocetine (40 mg) on flunitrazepam-induced impairment of memory in 8 normal volunteers. Treatment with vinpocetine led to improvements in short-term memory.
Hindmarch et al. (1991) studied the efficacy and tolerability of orally administered vinpocetine in patients with mild to moderate organic psychosyndromes including primary dementia. In the conditions of a placebo-controlled, randomized double-blind, multicentre trial 203 patients have been distributed in groups to receive daily 30 mg vinpocetine, 60 mg vinpocetine, or placebo for 16 weeks. Statistically significant improvements were found in vinpocetine groups in comparison with placebo in the clinical global impression and cognitive performance.

Other effects

Ribari et al. (1976) found a significant improvement of speech-audiograms of patients with sensorineural impairments of hearing after administration of 15 mg vinpocetine daily for 1-5 months.
Kahán and Oláh (1976) demonstrated that vinpocetine (20 mg in drop infusion or 10 mg i.v. three times daily) improved considerably the visual acuities in 100 arteriosclerotic patients. Improvement was most pronounced in occlusions and retinopathies associated with atherosclerosis of the central retinal artery.
Dutov et al. (1986) studied the effect of vinpocetine 15-45 mg daily and a combination of vinpocetine with different anticonvulsants in different forms of epilepsy. In 20 of the 31 patients studied vinpocetine either significantly decreased the frequency of the attacks or abolished them. Most pronounced effect was observed in generalized tonic-clonic convulsions especially when combined with absences. The clinical improvement not always correlated with EEG normalization. The mechanism of the anticonvulsive action of vinpocetine might be explained by normalization of the cerebral blood flow, by its antihypoxic action, or by a presence of own anticonvulsive properties.
Kis (1990) investigated the effect of vinpocetine when applied in addition to the standard hormone replacement therapy on 40 postmenopausal women. Vinpocetine significantly improved the effects of the hormone replacement therapy, and the author recommends such a combination therapy for alleviation of the menopausal complaints in postmenopausal women.


Numerous clinical studies indicated that vinpocetine is safe during long-term administration. No serious side effects related to the treatment have been found (Balestreri et al., 1987; Kis, 1990; Feigin et al., 2001).
Szobor and Klein, (1976) established that vinpocetine (10-30 mg daily at combined oral and i.m. administration, or 30-45 mg daily orallly) did not change laboratory tests, blood pictures, blood sugar, liver functions, did not cumulate and did not produce allergic symptoms).
There are few reports about side effects of vinpocetine after i.v. administration. Some patients had a passing sensation of warmth after injection of the drug (Orosz et al., 1976; Hajiev and Yancheva, 1976; Ribári et al., 1976)




Akopov SE, Gabrielian ES. (1992) Effects of aspirin, dipyridamole, nifedipine, and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination. Eur J Clin Pharmacol, 42(3): 257-259.
Balestreri R, Fontana L, Astengo, F. (1987) 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(5): 425-430.
Bhatti JZ, Hindmarch I. (1987) Vinpocetine Effects on Cognitive Impairments Produced by Flunitrazepam. Inter Clin Psychopharmacology, 2: 325-331.
Bencsáth P, Debreczeni L, Takács L. (1976) Effect of ethyl apovincaminate on cerebral circulation of dogs under normal conditions and arterial hypoxia. Arzneim-Forsch, 26 (10a): 1920-23.
Bonoczk P, Gulyas B, Adam-Vizi V, et al. (2000) Role of sodium chanel inhibition in neuroprotection: effect of vinpocetine. Brain Res Bull, 53(3): 245-54.
Burtsev EM, Savkov VS, Shprakh VV, Burtsev, ME. (1992) 10-years experience with using Cavinton in cerebrovascular disorders. Zh Nevropatol Psikhiatr Im S S Korsakova, 92(1): 56-60.
DeNoble VJ, Repetti SJ, Gelpke LW et al. (1986) Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav, 24(4): 1123-8.
Dutov AA, Tolpyshev BA, Petrov AP, Gladun VN. (1986) Use of cavinton in epilepsy. Zh Nevropatol Psikhiatr Im S S Korsakova, 86(6): 850-5.
Feigin VL, Doronin BM, Popova TF et al. (2001) Vinpocetine treatment in acute ischaemic stroke: a pilot Single-blind randomized clinical trial. Eur J Neurol, 8(1): 81.
Gulyas B, Bonoczk P, Vas A et al. (2001) The effect of a single-dose intravenous vinpocetine on brain metabolism in patients with ischemic stroke. Orv Hetil, 142(9): 443-9.
Hadjiev D, Yancheva S. (1976) Rheoencephalographic and psychological studies with ethyl apovincaminate in cerebral vascular insufficiency. Arzneim-Forsch, 26(10a): 1947-1950.
Hayakawa M. (1992) Effect of vinpocetine on red blood cell deformability in stroke patients. Arzneim-Forsch, 42(4): 425-7.
Hindmarch I, Fuchs HH, Erzigkeit H. (1991) Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol, 6(1): 31-43.
Itoh T. (1982) Effect of vinpocetine on platelet aggregation in patients with cerebrovascular diseases. Jap Pharmacol Ther, 205: 1481-1485.
Kahan A, Olah M. (1976) Use of ethyl apovincaminate in ophtalmological Therapy. Arzneim-Forsch, 26 (10): 1969-72.
Karpati E, Szporny L. (1976) General and cerebral haemodynamic activity of ethyl apovincaminate. Arzneim-Forsch, 26 (10): 1908-12.
King G, Narcavage D. (1986) Comparison of the effect of vinpocetine, vincamine, phenytoin, and cinnarizine in a rat model of cerebral ischaemia. Drug Develop Res 9: 225-234.
Kiss B, Karpati E. (1996) Mechanism of action of vinpocetine. Acta Pharm Hung, 66 (5): 213-24.
Kiss E. (1990) Adjuvant effect of cavinton in the treatment of climacteric symptoms. Ther Hung, 38(4): 170-3.
Kiss B, Cai NS, Erdo SL. (1991) Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies. Eur J Pharmacol, 209(1-2):109-12.
Krieglstein J, Rischke R. (1991) Vinpocetine increases the neuroprotective effect of adenosine in vitro. Eur J Pharmacol, 205(1): 7-10.
Lakics V, Sebestyen MG, Erdo SL. (1995) Vinpocetine is a highly potent neuroprotectant against veratridine-induced cell death in primary cultures of rat cerebral cortex. Neurosci Lett, 185(2): 127-30.
Lamar JC, Poignet H, Beaughard M et al. (1988) Calcium antagonist activity of vinpocetine and vincamine in several models of cerebral ischaemia. Drug Develop Res, 14: 297-304
Maslarova J, Nikolov R. (1999) Antihypoxic effect of vinpocetine. Works of the Chemical Pharmaceutical Research Institute, XIX, 175-182 (In Bulgarian).
Miyazaki M. (1995) The effect of cerebral vasodilator, vinpocetine, on cerebral vascular resistance evaluated by the Doppler ultrasonic technique in patients with cerebrovascular diseases. Angiology, 46(1): 53-8.
Orosz E, Deak Gy, Benoist,Gy. (1976) Effect of ethyl apovincaminate on the cerebral circulation. Arzneim-Forsch, 26(10a): 1951-56.
Pálosi É, Szporny L. (1976) Effect of ethyl apovincaminate of the central nervous system. Arzneim-Forsch, 26(10a): 1926-29.
Ribári O, Zelen B, Kollár B. (1976) Ethyl apovincaminate in the treatment of sensorineural impairment of hearing. Arzneim-Forsch, 26(10): 1977-80.
Rischke R, Krieglstein J. (1990) Effects of vinpocetine on local cerebral blood flow and glucose utilization seven days after forebrain ischaemia in the rat. Pharmacology, 41(3): 153-60.
Rischke R, Krieglstein J. (1991) Protective effect of vinpocetine against brain damage caused by ischaemia. Jpn J Pharmacol, 56(3): 349-56.
Szmolenszky T, Török B. (1976) Effect of ethyl apovincaminate on cerebral, carduac and renal flow rate in dogs in the course of administration. Arzneim-Forsch, 26 (10a): 1914-7.
Solti F, Iskum M, Czakó E. (1976) Effect of ethyl apovincaminate on the cerebral circulation. Arzneim-Forsch, 26(10): 1945-7.
Stolc S. (1999) Indole derivatives as neuroprotectants. Life Sci, 65(18-19): 1943-50.
Szakall S, Boros I, Balkay L, et al. (1998) Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study. J Neuroimaging, 8(4): 197-204.
Szobor A, Klein M. (1976) Ethyl apovincaminate therapy in neurovascular disease. Arzneim-Forsch, 26(10): 1984-89.
Tamaki N, Kusunoki T, Matsumoto S. (1985) The effect of vinpocetine on cerebral blood flow in patients with cerebrovascular disordes. Therapia Hungarica, 33:13-21.


Focus on Vinpocetine. First Published in Pharmacy On-Line Version 1.0 March 2001


Home • Journals • Search • Rules for Authors • Submit a Paper • Sponsor us
Rules for Authors
Submit a Paper
Sponsor Us

Google Search

Advanced Search


Default text | Increase text size