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Vinpocetine is a compound from the Periwinkle plant that is used as a cognitive protective and anti-aging agent. One of the more common of the nootropics, Vinpocetine may enhance blood flow and is touted to increase memory; this latter claim has not been investigated.

Our evidence-based analysis on vinpocetine features 153 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Vinpocetine

1Sources and Composition


Vinpocetine (also referred to as ethyl apovincaminate) is derived from the compound Vincamine, which is the principle active ingredient of the plant Vinca Minor (periwinkle) at 25-65% of the total alkaloids;[2] it was first synthesized in 1978 (under the brand name Cavinton)[3][4] and has since been used for the treatment of cerebrovascular disorders and cognitive impairment.[5]]

The periwinkle plant itself has traditional usage for the treatment of headaches.

Vinpocetine is a synthetic alkaloid that is derived from vincamine, a component of periwinkle plants. It has usage in medicine for neuroprotection following brain injury and usage in the supplement industry for preventing cognitive decline during aging


Vinpocetine ((3α,16α)-eburnamenine-14-carboxylic acid ethyl ester or ethyl apovincaminate) is an alkaloid with a molecular weight of 350.5g/mol[6] which is fully soluble in methanol, dimethyl sulfoxide, and acetone.[3] The structure of vinpocetine is based off of the cis(3S,16S)-eburnamenine skeleton structure, which is the following 5-ringed structure.[7][8]



Vinpocetine has been noted to have a bioavailability of 6.2-6.7% or so in humans when taken in aqueous solution[9][9][10] although it has a much higher bioavailability in rats at around 52%;[9] one human study has suggested that vinpocetine can have a similar bioavailability (56.6+/-8.9%) but this result seems unreliable.[11]

Omeprazole has been found to not significantly influence bioavailability of 2mg/kg vinpocetine[12] although ingesting vinpocetine with a meal can increase bioavailability by 60-100% (relative to fasted conditions).[13] Delivery systems can also increase absorption, including self-emulsifying (1.72-fold)[14] and proliposomes (3.5-fold).[15]

Vinpocetine appears to have decent bioavailability in rats, but poor bioavailability in fasted humans. It may need to be taken alongside food, which increases its bioavailability


Vinpocetine (ethyl apovincaminate) is fairly rapidly metabolized into cis-apovincaminic acid, which is thought to be its active metabolite.[16][9][17]

No detectable unchanged vinpocetine is excreted in the urine[11], as it is excreted after ester cleavage.[18]


Oral administration of a vinpocetine 5mg tablet has resulted in a Cmax of 63.69+/-8.32ng/mL at a Tmax of 1.46+/-0.14h with a half-life of 1.36+/-0.27h and an AUC of 202.48+/-14.48ng/h/mL.[19] It appears in serum fairly rapidly, within 20 minutes (albeit with equally fast metabolism).[20]

When looking at the half-life of vinpocetine, it appears to be reported in the range of 1.46 hours[19] and biphasic;[11] within 2-3 hours post ingestion vinpocetine does not appear to be detectable in the blood anymore.[21][17]

The volume of distribution appears to be 246.7+/-88.55 1 (3.2+/-0.9L/kg)[16] and total plasma clearance is 66.7+/-17.9L/h (0.88+/-0.20 L/h/kg).[18] Vinpocetine appears to bind extensively to plasma proteins, with numbers ranging from above 86.6% to complete binding.[7]

Vinpocetine itself is rapidly absorbed and rapidly metabolized into cis-apovincamic acid, and vinpocetine itself is not detected in the blood a few hours after oral administration

When looking at the main metabolite (apovincamic acid), it appears to peak within one hour of ingestion to approximately 100ng/mL and normalize within 3-4 hours following ingestion of 5-10mg vinpocetine.[21] Elsewhere, a 10mg dosage of vinpocetine has led to 49.5-51.4ng/mL Cmax at 1.02-1.11h Tmax[22] and vinpocetine has been found to degrade in a fairly constant ratio to its absorption rate (being degraded within 20 minutes of oral ingestion).[20]

cis-apovincamic acid appears to have a rapid spike in the blood due to the rapid conversion of vinpocetine

2.4Bioaccumulation and Excretion

There does not appear to be appreciable accumulation of vinpocetine in the body following oral ingestion of standard dosages (15-30mg daily).[21]

2.5Neurological Kinetics

Vinpocetine is able to effectively penetrate the blood-brain barrier in monkeys[23] and humans.[24] It is rapidly absorbed into the brain (3.18–4.27% of an injected dose within 2 minutes in humans[24] and up to 3.84% of total dose in monkeys[23]) and due to these concentrations exceeding the relative weights of the brain (1.7% and 1.8%, respectively) it is thought that this signifies not only easy permeability but selective accumulation.[7]

Vinpocetine's absorption into the brain via the blood brain barrier is rapid and nearly complete, and vinpocetine appears to accumulate in the brain shortly after ingestion

Vinpocetine appears to be more active and accumulated in the thalamus, basal ganglia, putamen, and visual cortex[25][24] as assessed by glucose utilization and bioaccumulation[26] and in one case blood flow enhancment.[25] It has been reported to be at 24% higher concentrations in the thalamus (relative to a reference region that did not experience disproportionate accumulation) and 18% higher in the striatum.[7]

Vinpocetine is detectable in the brain, and appears to favor accumulation in some specific neuroorgans (thalamus, striatum, basal ganglia, putamen, and visual cortex)

2.6Topical Administration

Vinpocetine appears to be able to be topically absorbed through the skin when a part of a microemulsion to enhance permeability (mostly Labrasol and Transcutol P)[27] and has also been formed into sugar esters proniosomes (converted to niosomes upon hydration,[28] niosomes being a vesicle formed from cholesterol and non-ionic surfactant[29]) which can be topically absorbed, and a patch containing 5mg of vinpocetine has been found to have a Tmax of 11.67+/-1.15h and a Cmax of 12.44+/-1.87ng/mL with a half-life of 13.94+/-1.2h, the overall AUC (417.70+/-50.27ng/h/mL) was approximately double that of oral ingestoin which demonstrates higher bioavailability.[19]



Vinpocetine is reported to be a phosphodiesterase (PDE) inhibitor selective for PDE1 but not further selective among subsets of PDE1 with IC50 values of 19μM,[30][31] 21μM,[32] or within the aforementioned range.[33] Infrequently, a lower potency of 100μM or so is reported[34] and Ki values have been reported to be in the 15-22.2μM range[31] up to 50.5μM.[35] The large variance is thought to be due to differences between tissue cultures and species.[7] It is a noncompetitive inhibitor with the presence of calmodulin not affecting inhibitory potential[32] and it has been confirmed in vivo albeit at very high doses of 20mg/kg injections.[36]

Vinpocetine has been noted to increase cGMP concentrations (indicative of PDE1 inhibition, as adenylate cyclase was unaffected) at 10μM, with a nonsignificant trend at 1μM.[32] Elsewhere, this has been noted to only occur with noradrenaline or potassium stimulation but not inherently[31] and this increase in cGMP (also downstream of nitric oxide signalling) is thought to underlie the vasodilating effects of vinpocetine.[7]

Inhibition towards cAMP phosphodisterases has been noted to be greater than 300-500μM,[37][31][32] and due to the relative inefficacy on other phosphodiesterase enzymes mediating cAMP it is seen as cGMP or PDE1 selective.[7]

Vinpocetine is a noncompetitive inhibitor of PDE1 enzymes, which subsequently raises cGMP concentrations and promotes vasorelaxation. The concentration that this occurs at is plausible, but also may be higher than achieved with oral supplementation (additionally, most literature on PDE1 inhibition is done in vitro only with the limited studies in rats using inpractically high doses)

Vinpocetine appears to be a sodium channel inhibitor[7] at site 2 with an IC50 of 1.6µM[24] and at NaV1.8 (IC50 3.5µM),[38] although it has affinity for NaV1.5 channels, it is significantly weaker (44µM) but still comparable to phenytoin.[39] Vinpocetine has been reported to inhibit batrachotoxin (poison dart frog toxin) binding to sodium channels with an IC50 of 0.34µM.[40]

Vinpocetine can also inhibit L-type calcium channels[41][42] either directly with an IC50 between 2.1-4.1µM[24] or indirectly via inhibiting sodium channels.[43][41] These inhibitory effects are thought to underlie some suppressive effects on neurotransmitter release.[44]

Vinpocetine has also been implicated in enhancing potassium current (low-threshold fast inactivating) in the 1-100µM range[45][46] whereas the slow activating channels are slightly suppressed[46] and calcium dependent potassium channels also suppressed;[47] overall potassium influx is inhibited with vinpocetine usage (76% at 30µM[48]). Potassium channel blockers are associated with memory enhancement (see the memory section on Agmatine for more information), so this is a possible mechanism underlying the supposed cognitive enhancing properties of vinpocetine despite the effects of this in vivo currently being unclear.

Vinpocetine can inhibit sodium and calcium channels, and these mechanisms are thought to underlie the interactions with many neurotransmitters and their release from neurons. Due to occurring at a much lower (more potent) concentration, it is plausible that these mechanisms underlie some of the activity of vinpocetine

Independent of the above two mechanism, vinpocetine may also inhibit IKKβ activation which subsequently impairs NF-kB translocation and subsequent inflammatory processes.[49] This appears to be a direct action independent of sodium and potassium channels as well as independent of known PDE interactions, and has an IC50 of 17.17 μM.[49]

Inhibition of IKKβ is a third mechanism of vinpocetine (albeit not unique among supplements) that underlies antiinflammatory properties of vinpocetine. The practical significance of this towards supplementation is not known

There appear to be interactions with adrenergic receptors directly, including a binding affinity for the adrenergic alpha-1a (2.9µM), alpha-2a (1.9µM), and alpha-2b (0.9µM). The adenosine A1 receptor also has a high affinity for vinpocetine at 8.3µM, and peripheral GABAA receptors (at the benzodiazepine binding site) appear to have an affinity for vinpocetine at 0.2µM (much less potency on central GABAA receptors at more than 10µM)[24]

Appears to have affinity for other receptors, mostly alpha adrenergic receptors and peripheral (but not central) GABAA benzodiazepine receptors. The affinity towards these receptors is quite respectable, and their interactions are probably relevant to nutritional supplementation


It has been noted that TPSO (overview in the GABAergic Neurotransmission section) associates with proteins of the mitochondria[50][51] and that vinpocetine (25μM) can reduce the loss in mitochondrial membrane potential caused by excitotoxicity which is thought to be in part mediated by TPSO (as other TPSO ligands were also neuroprotective, but to varying degrees).[52]

The impairment of mitochondrial function via beta-amyloid pigmentation appears to be attenuated with vinpocetine, albeit at a very high concentration of 40mM.[53]

Mitochondrial function appears to be supported with vinpocetine in vitro, although it is not ascertained how relevant this information is to oral supplementation. This may just be an outcome associated with the neuroprotective effects of vinpocetine

It has been noted that vinpocetine infusions have failed to significantly increase glucose metabolism in the brain of persons given an infusion of vinpocetine, but that the reduced turnover was nonsignificantly attenuated[54] while elsewhere it has been noted to slightly increase glucose turnover in stroke patients.[55][56]

There may be a slight increase in glucose consumption of the brain following vinpocetine administration, but there are no studies in otherwise healthy persons using oral supplementation at this moment in time

3.3Blood Flow and Oxygenation

In six otherwise healthy adults males, an infusion of 20mg vinpocetine (5% dextrose) and measurements over 20 minutes reported a 7% increase in cerebral blood flow relative to placebo.[1] This method of administration (20mg infusion) has been noted to improve blood flow in persons who suffered a stroke without significantly affecting mean arterial pressure.[57] This effect persists over 14[54] and 90 days[58] and is associated with cognitive protective effects.[58]

According to one PET study, vinpocetine has been noted to increase cerebral microcirculation,[55] which may be related to the ability of vinpocetine to enhance red blood cell (RBC) deformability[59] and thus reduce viscosity of the blood.[60]

In stroke patients or persons with cerebrovascular diseases, there are improvements in oxygenation status with 30-45mg oral vinpocetine (associated with improvements in memory and alertness)[61] and parachymal oxygen extraction.[57]

Vinpocetine appears to enhance cerebral blood flow, which is thought to be secondary to a slight vasodilatory effect. Due to not signficicantly affecting oxygenation inhernetly but increasing blood flow, there is a small increase of oxygenation status of the brain

3.4Memory and Cognition

PDE1 inhibition has been linked to improving cognition in animals exposed to neurotoxins (in these papers, alcohol)[36][62] which has been confirmed with 20mg/kg injections of vinpocetine;[36] the accumulation of cGMP likely positively regulates neural plasticity[63] (as that is known to occur when eNOS creates cGMP[64]) and does not necessarily require cognitive damage as a prerequisite.[63] As mentioned earlier, it is unsure how relevant the above mechanisms are due to requiring a very high dose of vinpocetine to reach the IC50 concentrations.

Inhibition of sodium and calcium channels is also associated with memory improvement (evidenced by the inhibitor RGH-2716[65]), and due to vinpocetine sharing these properties it is thought that it may be a mechanism underlying memory enhancement from vinpocetine.[66] The interactions of vinpocetine at alpha-adrenergic receptors and augmenting noradrenergic activity in the locus coeruleus[67] also appears to be related to memory enhancement,[68] and the autoinhibition of this effect at 1mg/kg injections (but not lesser amounts) fits in well with the observed bell-curve seen in interventions with vinpocetine.

Another possible mechanism is potentiation of LTP (long term potentiation) which has been noted in vitro in hippocampal slices with a concentration of 0.1µM vinpocetine, although 1µM was slightly less effective and 0.01µM having a nonsignificant trend to augment LTP.[69] This appeared to be additive with similar concentrations of idebenon (a derivative of CoQ10),[69] and although this was not hypothesized by the authors the activation of the locus coeruleus has been noted to increase hippocampal LTP.[70]

Vinpocetine mas mechanisms to increase memory formation. While the most popular mechanisms attributed to vinpocetine (PDE1 inhibition) appears to be overblown and probably not relevant, both the inhibition of sodium channels and the interactions with adrenergic receptors are implicated in increasing memory formation

In rat models of glutaminergic neurotoxicity, vinpocetine and its active metabolite can both preserve memory formation which is hindered in neurotoxic control (assessed by water morris maze, a spatial memory task).[71] Vinpocetine has also shown protective effects against scopolamine induced amnesia,[66][72] diabetes-induced cognitive impairment,[73] hypoxia induced impairment,[72] and impairment from Rohypnol.[74]

Vinpocetine appears to be protective against toxin-induced amnesia, suggesting an interaction between the neuroprotective effects and memory formation

For studies using water mazes in cognitively healthy rats to assess spacial memory, vinpocetine (10mg/kg) or its active metabolite over five days does not appear to outperform control[71] and a water labyrinth task also fails to show benefit to cognitively healthy young rats (although older rats noted a small amount of benefit).[66] 

One study has noted benefits to cognition in rats, specifically retrieval of memory, as assessed by a step-down passive avoidance task in rats given either 18-30mg/kg vinpocetine orally with both higher and lower doses being ineffective.[75] Oddly, the primary metabolite of vinpocetine (apovincamic acid) was ineffective.[75]

Memory scanning speed has been noted to be increased with vinpocetine at 40mg (but not 10-20mg) in otherwise healthy young adult females, but this does not necessarily reflect memory formation (just suggestive thereof).[76]

There is contradictory information as to whether vinpocetine can cause improvements in memory formation and cognition with acute supplementation, but if this is to occur it would with higher dosages (40mg to improve reaction speed, and an estimated human equivalent of 2.88mg/kg for retrieval

3.5Processing Speed and Attention

Vinpocetine in otherwise healthy adult females (40mg divided into thrice daily dosing) appears to reduce reaction time on memory scanning tests from approximately 610ms to 430ms, whereas 10mg and 20mg were ineffective.[76]

Increased reaction speed, as well as increased processing speed, have been seen in a rehabilitative setting with NFL football players (although highly confounded with Acetyl-L-Carnitine, Fish Oil, Alpha-Lipoic Acid and Huperzine-A)[77] and elsewhere with vinpocetine (10mg) paired with Ginkgo biloba (40mg) and micronutrients.[78]

One study has noted an improvement in reaction speed and performance on a memory test due to increased reaction speed with 40mg vinpocetine, but other studies assessing reaction speed or attention are confounded with the inclusion of other compounds


Vinpocetine is a NaV1.8 sodium channel blocker (3.5µM)[38] and this channel appears to be associated with chronic pain (in the sense that activity of this channel causes pain and inhibition or downregulation reduces pain).[79][80][81] Vinpocetine does not appear to inhernetly inhibit the channel, but it has high affinity for activated channels and causes a hyperpolarization and reduced signalling.[38]

3.7Adrenergic Neurotransmission

Vinpocetine appears to have micromolar affinity towards a variety of alpha-adrenergic receptors including the 1a subset (2.9µM), 2a (1.9µM), 2b (0.9µM) with other adrenergic receptors being classified as 'above 10µM' (and comparatively weaker affinity).[24] Vinpocetine does not appear to inhibit adrenergic activity at 1µM[82] and due to augmenting the noradrenergic firing of the locus coeruleus with an ED50 of 750µg/kg (injections of vinpocetine)[67] it is thought that vinpocetine may be an agonist of the alpha-1 receptor, since this receptor is known to augment firing of the locus coeruleus.[83][84]

1mg/kg of vinpocetine as injections is able to inhibit the aforementioned potentiation of signalling, but due to affecting more than just adrenergic neurons it is thought to be mediated via a different mechanism.[67]

At least one study has suggested that injections of 2mg/kg can cause beta-adrenergic receptors to have more affinity for their ligands,[85] but this has not been reproduced.

Vinpocetine appears to have affinity for alpha-adrenergic receptors, with a strong enough potency that they are probably relevant following oral ingestion of vinpocetine supplements. Not much is known about how vinpocetine acts with these receptors, but it may be an agonist

3.8Dopaminergic Neurotransmission

Vinpocetine has been implicated in reducing intracellular dopamine concentrations (with an increase in the dopamine metabolite DOPAC) in isolated striatum nerve endings via a mechanisms independent of its interaction with sodium channels[86][87] and also increasing external DOPAC concentrations.[87] This increase in DOPAC at expense of dopamine is known to occur with MAO activators[88] but this does not appear to be the case with vinpocetine, and an impairment of vesicular storage of dopamine is thought to be the cause.[86]

Vinpocetine does not significantly affect the release rate of dopamine into the synapse invoked by high potassium,[86][87] although it effectively inhibits the dopamine release caused by sodium channel activators (in accordance with its sodium channel blocking ability),[86][87] glutamate,[89] and methamphetamine.[90] When there is no significant stressor causing a release of dopamine, basal dopamine kinetics do not appear to be affected as vinpocetine does not appear to be inherently suppressive.[89][86][87]

25µM vinpocetine appears to inhibit dopamine uptake into isolated striatal neurons (to 32.9% of untreated control), which was slightly less effective than 1µM of reserpine (18.7%)[91] although 5µM does not appear to alter affinity for the transporter.[90] Vinpocetine (5µM) does not appear to influence dopamine receptor density.[90] Vinpocetine has been noted to have affinity for dopaminergic D2 and D4 receptors (IC50 of 7.9µM), but it is not sure if this is an agonistic or antagonistic property.[24]

Overall, high concentrations of vinpocetine appear to have antidopaminergic properties (reducing vesicular storage without impairing basal release, inhibting dopamine uptake) but it is not sure how relevant this is to oral vinpocetine supplementation due to the concentrations required. There are no studies in living creatures yet

In cells treated with 3-NPA (mitochondrial toxin[92] with particular efficacy in the striatum[93][94]) vinpocetine at 25µM appears to exert protective effects by trending to normalize dopamine concentrations with a potency similar or slightly lesser than 50µM Vitamin E.[91]

In rats treated with rotenone (to induce Parkinson's like symptoms), oral supplementation of vinpocetine at 3-6mg/kg daily was able to preserve motor function and striatal dopamine concentrations (both to a greater degree than 100-200mg/kg Piracetam) and reduced oxidative parameters with a near normalization of MDA at 6mg/kg.[95]

In response to toxins that normally reduce dopamine levels, oral vinpocetine may exert a protective effect and act to normalize changes in dopamine. The magnitude of neuroprotection seen appears to be greater than many other dietary supplements as it nearly normalizes parameters, and this may be relevant to oral supplementation

3.9Glutaminergic Neurotransmission

Vinpocetine has shown protective effects against glutaminergic excitotoxins[96] and hypoxic/ischemic damage[97][98] (known to involve excitatory signalling[99]) which appears to extend to its active metabolite, cis-apovincaminic acid.[71]

Vinpocetine has been found to reduce glutamate binding to AMPA receptors, albeit weakly with 27% inhibition at 1µM and 50% inhibition occurring at 100µM.[89] The NMDA antagonist CPP and kainate were not affected by vinpocetine up to this concentration, although since NMDA signalling was attenated a bit it was thought that vinpocetine was a weak and nonselective antagonist of NMDA receptors that was just outcompeted by CPP.[89] Glutamate induced neurotoxicity has also been found to be attenuated with TPSO ligands, but weakly so (and thus this is likely not the mechanism pertaining to vinpocetine in regards to glutaminergic neurotransmission).[52] Furthermore, the NMDA agonist MK-801 has been twice displaced from the membrane by vinpocetine.[89][100]

It appears that vinpocetine may act at the level of the glutaminergic receptors, and inhibits signalling via AMPA and NMDA (two subsets of glutaminergic receptors) without significantly affecting kainate signalling. The potency at this stage seems to be fairly weak, but may be relevant

Vinpocetine is a sodium channel inhibitor, and it appears to have efficacy on a variety of research drugs that activate sodium channels including 4-aminopyridine,[101] veratridine,[102][103] with these effects occurring in the 2.5-15μM range and sometimes abolishing neurotransmitter release from the aforementioned drugs.[102] There are less reliable effects in inhibiting potassium-induced neurotransmitter release, either being effective at the standard 15-50μM concentration (44-83% inhibition)[104] (inefficacy also noted at this concentration[44]) or requiring a much higher dose (5mM) to become appreciable.[102]

Vinpocetine appears to reduce neurotransmitter (in this sense, glutamate) release from neurons secondary to inhibiting sodium channels. Although it has mixed evidence assessing the effects of potassium-induced release, drugs that work by the sodium channels are potently inhibited and their neurotranmission reduced

The pro-epileptic drug 4-aminopyridine (induces glutamate release[105] related to a neuronal influx of calcium[101] and sodium[106] and causes seizures[107][108]) appears to be inhibited in vitro by vinpocetine blocking sodium channels, which also inhibits calcium influx at a concentration of 2.5-25μM[101] and prevents the subsequent glutamate release.[108]

This antiepileptic potential has been noted in vivo in guinea pigs (2-10mg/kg).[109][110]

In vitro studies using epileptic toxins and drugs note that vinpocetine is able to confer anti-epileptic effects, and there is some animal evidence to suggest the standard dosages of vinpocetine are able to reduce epileptic potential

3.10GABAergic Neurotransmission

Vinpocetine appears to have some actions through peripheral benzodiazepine receptors (also known as the 18kDa translocator protein or TSPO system)[23] [111][112] with an IC50 of 0.2µM,[23][24] the peripheral GABAA receptors are expressed mostly in glial cells (quite limited in neurons)[113][114] but play less of a role in cognitive relative to central receptors (which vinpocetine has a weaker affinity for, with an IC50 greater than 10µM).[24] This has been confirmed to occur in the brain at an intramuscular dose of 3mg/kg in cynomolgous monkeys, as assessed by studies using vinpocetine to displace the known agonist isoquinoline carboxamide (PK11195).[23]

Vinpocetine appears to be a potent ligand for the peripheral, but not central, GABAA receptor at the benzodiazepine binding site. This appears to occur in the brain following injections, which suggest interactions with glial cell function

3.11Neuroinflammation and Microglial Activation

Microglia (neuronal support cells) are cells that are activated via inflammatory stressors during stroke and ischemia[115] and the TPSO system (peripheral GABAA receptors) are known to be upregulated in neuroinflammatory states including stroke, aging, and cognitive decline[116][117] as it is a molecular sensor of neural injury.[118] TPSO expression is thought to be a reliable biomarker of microglia activation.[118]

Anti-inflammatory properties can come from direct inhibition of IKKβ [49][119] causing reduced translocation of NF-kB.[120]

Antiinflammatory properties have been noted in mice given 5mg/kg vinpocetine daily for a week (injections).[120]

Vinpocetine appears to have anti-inflammatory properties in vitro, and they appear to be relevant during administration of the standard dosages of vinpocetine


The TPSO system (molecular sensor of brain injury and microglia activation[118]) is upregulated in the aging brain that is not afflicted with cognitive degeneration in all tested species[121][122][123] including humans[124] but is also upregulated in states of cognitive impairment[125] or neurotrauma.[126] As mentioned elsewhere, vinpocetine has affinity for the TSPO receptor system with an IC50 of 200nM (0.2µM).[23][24][115]

The TSPO system (of which vinpocetine is a high affinity ligand for) is known to be upregulated during aging

4Cardiovascular Health


In ApoE deficient mice given 5mg/kg vinpocetine (injections every other day) for 16 weeks, there appeared to be a near halving of atherosclerotic buildup.[127] This was deemed unrelated to the reduction in blood pressure (usually not associated in this rat model[128]) and was attributed to a concentration dependent reduction in LDL oxidation seen in vitro (30-50µM) which was related to a reduction in the receptor for oxidized LDL (LOX-1).[129] This may be related to the inhibition of IKKβ, as its target (NF-kB) is required in LOX-1 expression.[130]

In ApoE deficient mice, circulating levels of lipoproteins (LDL-C, HDL-C, etc.) do not appear to be significantly influenced.[127]

May reduce LDL oxidation rates and thus artherosclerotic formation independent of actually affecting lipoprotein concentrations. The mechanisms are thought to be related to the antiinflammatory properties of vinpocetine

During the process of atherosclerosis, the vasculature tends to undergo some remodelling associated with increased vascular smooth muscle cell (VSMC) proliferation which serve to further atherosclerosis.[131][132] Since the antiinflammatory action of inhibiting IKKβ was detected in VSMCs previously[49] and vinpocetine is known to benefit vasculature secondary to its PDE1 properties[130] it has been investigated how vinpocetine acts on VSMC proliferation. Vinpocetine has been implicated in reducing VSMC proliferation at 5mg/kg injections to about 50% of control, which was associated with preventing activation of ERK1/2 from PDGF.[133] As ERK1/2 activation via this means has been noted previously to be activated by oxidation,[134] it was thought that this protective effect was secondary to antioxidative properties (and the effects were mimicked by the antioxidant N-Acetylcysteine).[133]

5Interactions with Organ Systems


Oral administration of vinpocetine at 2.1-8.4mg/kg daily for 15 days alongside the hepatotoxin CCL4 was able to dose-dependently reduce the elevations of liver enzymes including ALT (49.3-63.6%), AST (10.5-27.2%), and ALP (52.5-64.9%) with a 82.6% reduction in necrosis at the highest dose; 8.4mg/kg had a potency not significantly different than the comparator of 30mg/kg silymarin (Milk thistle).[135]


Vinpocetine has been noted to protect from antibiotic-induced hearing loss with injections of 2mg/kg, with near absolute protection over the course of 180 days in guinea pigs[136] that may also apply to 4-aminopyridine induced hearing losses.[110]

6Interactions with Cancer Metabolism


Vinpocetine has been found to inhibit proliferation of breast cancer cells associated with stoppin the cell cycle at the G0/G1 phase and attenuated activation of PI3K and STAT3; vinpocetine had an inhibitory effect on cell viability with an IC50 of 23.5-32.2µM (range of four cell lines) and was effective in tumor bearing mice given 10-20mg/kg vinpocetine injections at the tumor site.[137]

Vinpocetine has suppressive effects on breast cancer cells, but since this occurs at a high concentration or injections near the tumor it is doubtful how practically relevant this information is

7Nutrient-Nutrient Interactions


Nitrate is a small molecule found mostly in beets and leafy green vegetables that increases nitric oxide in the body following ingestion. Chronic usage of nitrates or nitrate donors is known to induce a state of tolerance called 'nitrate tolerance'[138][139] which appear to be associated with an increase in the activity of PDE1A1.[130] Nitric oxide normally acts upon its receptor to increase cGMP concentrations,[140] and PDE1 enzymes (all isoforms) degrade cGMP[141][142][143] so an increase of the enzyme acts to normalize cGMP concentrations and thus the effects of nitric oxide. PDE1A1 does not fully explain nitrate tolernace, but plays a role.[130]

Vinpocetine is a PDE1 inhibitor,[7][32] and appears to partially restore tolerance to nitrates in vitro and augmented nitrate-induced vasodilation in already sensitive rings.[130]

Vinpocetine may reduce the tolerance to prolonged nitrate usage and also promote the vasodilating properties of nitrates

8Safety and Toxicity

8.1Case Studies

When used in hospital settings as IV administration, there have been reports of adverse effects such as death from drastic drops in blood pressure and pulse rate.[144][145] These effects have not yet been reported for orally supplemented vinpocetine at the standard dosages.

Contact dermatitis to vincamine has been reported,[146] and a case of agranulocytosis (acute reduction in white blood cell count) has been reported[147] and while it was also in a clinical setting it used 15mg vinpocetine daily.

Injections may reduce blood pressure, which are not thought to be relevant to oral ingestion. A lone case study has noted an acute reduction in white blood cell count at a dose that is relevant, but this topic has not been further investigated

8.2Pregnancy And Fetal Toxicity

Researchers have examined various doses of vinpocetine in a series of animal studies that looked at prenatal toxicity. They have found some worrying results, particularly at higher doses. The following refers to the results of a review.[148]

In one study, groups of 10 time-mated female Sprague Dawley rats were administered doses of 0, 20, 40, 80, 160, or 320 mg/kg of vinpocetine daily from the 6th day of gestation to the 20th. The highest dosed groups tended to have a higher rate of red or brown vaginal discharge. The 0, 20, 40, 80, 160, and 320 mg/kg groups had occurrences of 4, 5, 7, 10, 10, and 9, respectively. Discoloration of nares was found particularly in the 160 and 320 mg/kg groups, and piloerection was found in all rats in the 160 and 320 mg/kg groups. All animals survived.

Maternal body weights were substantially lower in the control group in the 80, 160, and 320 mg/kg groups, notably lower in the 40 mg group, and not lower in the 20 mg/kg group. This was partially due to a reduction in gravid uterine weight, but also independent to some extent. Recording of maternal feed intake was in concordance with this, and vinpocetine reduced consumption in a dose-dependent manner at doses higher than 20 mg/kg.

Percentage of post-implantation loss was (mean + standard error) 5.30 ± 1.78, 18.41 ± 11.70, 27.55 ± 12.35, 100.00 ± 0.00, 90.77 ± 9.23, and 100.00 ± 0.00 for the 0, 20, 40, 80, 160, and 320 mg/kg groups, respectively, the highest 3 being statistically significant. The number of resorptions per litter increased in a dose-dependent fashion, with the 3 highest dosings being statistically significant, and the number of live fetuses per litter declined in a dose-dependent fashion: 13.63 ± 0.53, 11.50 ± 1.78, 10.13 ± 1.85, 0.00 ± 0.00, 1.20 ± 1.20, and 0.00 ± 0.00 for the 0, 20, 40, 80, 160, and 320 mg/kg groups, respectively, the highest 3 being statistically significant.

There weren’t any statistically significant differences in fetal weight or external malformations of examined fetuses, though this was limited by there being either no or very few fetuses in three highest dose groups. Internal malformations weren’t evaluated in this study.

High doses of vinpocetine led to an anorexic effect on pregnant rats and notable fetal toxicity, with a high risk for miscarriages at the upper end of the dose range. It’s not possible to conclude that any of these doses are safe, but there was seen to be a direct dose-dependent effect.

In the follow-up study, groups of 25 time-mated female Sprague Dawley rats were administered doses of 0, 5, 20, or 60 mg vinpocetine/kg daily from the 6th day of gestation to the 20th. It aimed to assess adverse developmental effects so it used smaller doses that wouldn’t lead to as many miscarriages.

Maternal weight was somewhat lower in the 5 and 20 mg/kg groups, and substantially lower in the 60 mg/kg group, which was the only statistically significant reduction. Gravid uterine weight was somewhat lower in the 5 and 20 mg/kg groups and the lowest in the 60 mg/kg group than in the control group, but the only statistically significant difference was in the 60 mg/kg group. Interestingly, feed intake wasn’t different between the 0, 5, and 20 mg/kg groups, and was significantly lower in the 60 mg/kg group, but not by a great deal (nowhere close to the higher doses in the previously mentioned study). The 20 and 60 mg/kg groups saw a large increase in red and/or brown vaginal discharge, but not the 5 mg/kg group.

The number of live fetuses per litter for the various groups was as follows (mean + standard error): 13.95 ± 0.55, 11.95 ± 1.06, 11.86 ± 0.88, and 2.55 ± 1.00 for the 0, 5, 20, and 60 mg/kg groups, respectively, with only the 60 mg/kg group being statistically significantly lower than the control group. Of the live fetuses in the 60 mg/kg group, 82.19% were male, statistically significantly higher than the control group. Percentage post-implantation loss was 3.29 ± 1.33, 10.67 ± 5.29, 11.13 ± 4.65, and 83.13 ± 6.47 which was only statistically significant in the 60 mg/kg group compared with control.

Fetal weight declined a little in the 60 mg/kg group but it wasn’t statistically significant compared with control, and there was no significant difference in external abnormalities in fetuses across all groups. There were various observations of statistically significant increases in abnormalities of organs and skeletons of fetuses from the 5 mg, 20 and 60 mg/kg groups. Overall, it can be said that the risk for fetal abnormalities was possibly higher but roughly comparable to control for 5 mg, and significantly higher for 20 and 60 mg/kg.

Doses of 20 mg/kg or more in rats produced a higher rate of fetal abnormalities, and the 60 mg dose produced a statistically significant reduction in the number of fetuses and in maternal weight.

One other study in groups of 8 time-mated female rabbits used doses of 0, 25, 75, 150, or 300 mg/kg from the 7th day of gestation o the 28th. It found a dose-dependent reduction in maternal body weight for all doses higher than 25 mg/kg and a concomitant decrease in feed consumption. There was no notable maternal pathology. There was a statistically significant reduction in the number of live fetuses per litter in the 300 mg/kg group, and a nonsignificant decline in the 25, and 150 mg/kg groups, but not the 75 mg group. There were no notable differences between groups in fetal malformations of any type.

Very high doses in rabbits caused a higher rate of fetal toxicity and fewer births.

The authors noted that, in another paper, 5 mg/kg in rats produced a plasma level of vinpocetine and its main metabolite roughly equivalent to a single 10 mg dose in humans.[149] While there were no statistically significant differences in fetal toxicity measures for 5 mg/kg up to 20, small increases in risk are compatible with the results, and abnormalities in fetuses were statistically significant or suggestive for many areas in the 20 mg/kg groups or higher. 10-60 mg in humans is a common dose, so while there isn’t sufficient evidence to say that the lower end is harmful during pregnancy, caution would warrant limiting dose to 10 mg or less.

High doses of vinpocetine cause fetal toxicity and reductions in maternal weight and appetite in rats and rabbits. The higher end of usual human doses may lead to these effects, while the lower end of 10 mg hasn’t been sufficiently established to be harmful, but these studies don’t rule out harms in human pregnancy.


  1. ^ a b The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers.
  2. ^ Summary of Data for Chemical Selection: Vincamine.
  3. ^ a b Lörincz C, Szász K, Kisfaludy L. The synthesis of ethyl apovincaminate. Arzneimittelforschung. (1976)
  4. ^ Synthesis of Vinca Alkaloids and Related Compounds, XV1) A New Synthetic Route to (+)-Vincaminic and (+)-Apovincaminic Esters.
  5. ^ Bagoly E, Fehér G, Szapáry L. The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies. Orv Hetil. (2007)
  6. ^ Patyar S, et al. Role of vinpocetine in cerebrovascular diseases. Pharmacol Rep. (2011)
  7. ^ a b c d e f g h i Bönöczk P, et al. Role of sodium channel inhibition in neuroprotection: effect of vinpocetine. Brain Res Bull. (2000)
  8. ^ Syntheses and Cardiovascular Activity of Stereoisomers and Derivatives of Eburnane Alkaloids.
  9. ^ a b c d Szakács T, Veres Z, Vereczkey L. In vitro-in vivo correlation of the pharmacokinetics of vinpocetine. Pol J Pharmacol. (2001)
  10. ^ Grandt R, et al. Vinpocetine pharmacokinetics in elderly subjects. Arzneimittelforschung. (1989)
  11. ^ a b c Vereczkey L, et al. Pharmacokinetics of vinpocetine in humans. Arzneimittelforschung. (1979)
  12. ^ Sozański T, et al. Omeprazole does not change the oral bioavailability or pharmacokinetics of vinpocetine in rats. Pharmacol Rep. (2011)
  13. ^ Lohmann A, et al. Bioavailability of vinpocetine and interference of the time of application with food intake. Arzneimittelforschung. (1992)
  14. ^ Cui SX, et al. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine. Drug Dev Ind Pharm. (2009)
  15. ^ Xu H, et al. Optimized preparation of vinpocetine proliposomes by a novel method and in vivo evaluation of its pharmacokinetics in New Zealand rabbits. J Control Release. (2009)
  16. ^ a b Miskolczi P, et al. Effect of age on the pharmacokinetics of vinpocetine (Cavinton) and apovincaminic acid. Eur J Clin Pharmacol. (1987)
  17. ^ a b Chen J, et al. Determination of apovincaminic acid in human plasma by high-performance liquid chromatography using solid-phase extraction and ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. (2006)
  18. ^ a b Vereczkey L. Pharmacokinetics and metabolism of vincamine and related compounds. Eur J Drug Metab Pharmacokinet. (1985)
  19. ^ a b c El-Laithy HM, Shoukry O, Mahran LG. Novel sugar esters proniosomes for transdermal delivery of vinpocetine: preclinical and clinical studies. Eur J Pharm Biopharm. (2011)
  20. ^ a b Gulyás B, et al. Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine. Eur J Nucl Med Mol Imaging. (2002)
  21. ^ a b c Miskolczi P, et al. Pharmacokinetics of vinpocetine and its main metabolite apovincaminic acid before and after the chronic oral administration of vinpocetine to humans. Eur J Drug Metab Pharmacokinet. (1990)
  22. ^ 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)
  23. ^ a b c d e f Gulyás B, et al. Brain uptake and plasma metabolism of {11C}vinpocetine: a preliminary PET study in a cynomolgus monkey. J Neuroimaging. (1999)
  24. ^ a b c d e f g h i j k Gulyás B, et al. PET studies on the brain uptake and regional distribution of {11C}vinpocetine in human subjects. Acta Neurol Scand. (2002)
  25. ^ a b Vas A, et al. Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences. J Neurol Sci. (2002)
  26. ^ Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.
  27. ^ Hua L, et al. Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery. Drug Dev Ind Pharm. (2004)
  28. ^ Hu C, Rhodes DG. Proniosomes: a novel drug carrier preparation. Int J Pharm. (1999)
  29. ^ Non-ionic surfactant based vesicles (niosomes) in drug delivery.
  30. ^ Chiu PJ, et al. Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta. Am J Hypertens. (1988)
  31. ^ a b c d Ahn HS, et al. Effects of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta. Biochem Pharmacol. (1989)
  32. ^ a b c d e Hagiwara M, Endo T, Hidaka H. Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle. Biochem Pharmacol. (1984)
  33. ^ Rosdy B, Balázs M, Szporny L. Biochemical effects of ethyl apovincaminate. Arzneimittelforschung. (1976)
  34. ^ Dunkern TR, Hatzelmann A. Characterization of inhibitors of phosphodiesterase 1C on a human cellular system. FEBS J. (2007)
  35. ^ Yu MC, et al. Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced {3H}-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia. Eur J Pharmacol. (2010)
  36. ^ a b c Filgueiras CC, Krahe TE, Medina AE. Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation. Neurosci Lett. (2010)
  37. ^ Lindgren SH, et al. Effects of isozyme-selective phosphodiesterase inhibitors on rat aorta and human platelets: smooth muscle tone, platelet aggregation and cAMP levels. Acta Physiol Scand. (1990)
  38. ^ a b c Zhou X, et al. Vinpocetine is a potent blocker of rat NaV1.8 tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. (2003)
  39. ^ Vinpocetine is as potent as phenytoin to block voltage-gated Na+ channels in rat cortical neurons.
  40. ^ Erdo SA, et al. Vincamine and vincanol are potent blockers of voltage-gated Na+ channels. Eur J Pharmacol. (1996)
  41. ^ a b Tretter L, Adam-Vizi V. The neuroprotective drug vinpocetine prevents veratridine-induced {Na+}i and {Ca2+}i rise in synaptosomes. Neuroreport. (1998)
  42. ^ Kaneko S, Takahashi H, Satoh M. The use of Xenopus oocytes to evaluate drugs affecting brain Ca2+ channels: effects of bifemelane and several nootropic agents. Eur J Pharmacol. (1990)
  43. ^ Vas A, et al. Human positron emission tomography with oral 11C-vinpocetine. Orv Hetil. (2003)
  44. ^ a b Sitges M, Nekrassov V. Vinpocetine selectively inhibits neurotransmitter release triggered by sodium channel activation. Neurochem Res. (1999)
  45. ^ Solntseva EI, Bukanova JV. Enhancement of low-threshold A-current of the neuronal membrane by vinpocetine. Membr Cell Biol. (2000)
  46. ^ a b Bukanova JV, Solntseva EI, Skrebitsky VG. Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons. Int J Neuropsychopharmacol. (2002)
  47. ^ Solntseva EI, Bukanova JV, Skrebitsky VG. The nootropic drug vinpocetine modulates different types of potassium currents in molluscan neurons. Comp Biochem Physiol C Toxicol Pharmacol. (2001)
  48. ^ Bukanova YuV, Solntseva EI. Nootropic agent vinpocetine blocks delayed rectified potassium currents more strongly than high-threshold calcium currents. Neurosci Behav Physiol. (1998)
  49. ^ a b c d Jeon KI, et al. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci U S A. (2010)
  50. ^ Castedo M, Perfettini JL, Kroemer G. Mitochondrial apoptosis and the peripheral benzodiazepine receptor: a novel target for viral and pharmacological manipulation. J Exp Med. (2002)
  51. ^ Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. (2002)
  52. ^ a b Tárnok K, et al. Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons. Neurochem Int. (2008)
  53. ^ Pereira C, Agostinho P, Oliveira CR. Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells. Free Radic Res. (2000)
  54. ^ a b Szilágyi G, et al. Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study. J Neurol Sci. (2005)
  55. ^ a b Szakáll S, et al. Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study. J Neuroimaging. (1998)
  56. ^ The Effect of a Single-Dose Intravenous Vinpocetine on Chronic Stroke Patients. A PET Study.
  57. ^ a b Bönöczk P, Panczel G, Nagy Z. Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a near infrared spectroscopy and transcranial Doppler study. Eur J Ultrasound. (2002)
  58. ^ a b Kemény V, et al. Acute and chronic effects of vinpocetine on cerebral hemodynamics and neuropsychological performance in multi-infarct patients. J Clin Pharmacol. (2005)
  59. ^ Kuzuya F. Effects of vinpocetine on platelet aggregability and erythrocyte deformability. Ther Hung. (1985)
  60. ^ Osawa M, Maruyama S. Effects of TCV-3B (vinpocetine) on blood viscosity in ischemic cerebrovascular diseases. Ther Hung. (1985)
  61. ^ Szobor A, Klein M. Ethyl apovincaminate therapy in neurovascular diseases. Arzneimittelforschung. (1976)
  62. ^ Medina AE, Krahe TE, Ramoa AS. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. (2006)
  63. ^ a b van Staveren WC, et al. The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat. Brain Res. (2001)
  64. ^ Dinerman JL, et al. Endothelial nitric oxide synthase localized to hippocampal pyramidal cells: implications for synaptic plasticity. Proc Natl Acad Sci U S A. (1994)
  65. ^ 1-Oxa-3,8-diazaspiro{4.5}decan-2-one derivatives with a potent inhibitory effect on neural Ca-uptake and protecting action against TET-induced brain edema and memory and learning deficits.
  66. ^ a b c Paróczai M, Kiss B, Kárpáti E. Effect of RGH-2716 on learning and memory deficits of young and aged rats in water-labyrinth. Brain Res Bull. (1998)
  67. ^ a b c Gaál L, Molnár P. Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus. Eur J Pharmacol. (1990)
  68. ^ Lemon N, et al. Locus coeruleus activation facilitates memory encoding and induces hippocampal LTD that depends on beta-adrenergic receptor activation. Cereb Cortex. (2009)
  69. ^ a b Ishihara K, et al. Idebenone and vinpocetine augment long-term potentiation in hippocampal slices in the guinea pig. Neuropharmacology. (1989)
  70. ^ Harley C. Noradrenergic and locus coeruleus modulation of the perforant path-evoked potential in rat dentate gyrus supports a role for the locus coeruleus in attentional and memorial processes. Prog Brain Res. (1991)
  71. ^ a b c Nyakas C, et al. Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neurosci Ther. (2009)
  72. ^ a b DeNoble VJ, et al. Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav. (1986)
  73. ^ Deshmukh R, et al. Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine -- a PDE1 inhibitor. Eur J Pharmacol. (2009)
  74. ^ Bhatti JZ, Hindmarch I. Vinpocetine effects on cognitive impairments produced by flunitrazepam. Int Clin Psychopharmacol. (1987)
  75. ^ a b DeNoble VJ. Vinpocetine enhances retrieval of a step-through passive avoidance response in rats. Pharmacol Biochem Behav. (1987)
  76. ^ a b Subhan Z, Hindmarch I. Psychopharmacological effects of vinpocetine in normal healthy volunteers. Eur J Clin Pharmacol. (1985)
  77. ^ Amen DG, et al. Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation. J Psychoactive Drugs. (2011)
  78. ^ Polich J, Gloria R. Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Hum Psychopharmacol. (2001)
  79. ^ Lai J, et al. Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8. Pain. (2002)
  80. ^ Lai J, et al. Blockade of neuropathic pain by antisense targeting of tetrodotoxin-resistant sodium channels in sensory neurons. Methods Enzymol. (2000)
  81. ^ Gold MS, et al. Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J Neurosci. (2003)
  82. ^ Effect of vinpocetine on monoamine receptor binding and synaptosomal uptake in the rat brain.
  83. ^ Mouradian RD, Sessler FM, Waterhouse BD. Noradrenergic potentiation of excitatory transmitter action in cerebrocortical slices: evidence for mediation by an alpha 1 receptor-linked second messenger pathway. Brain Res. (1991)
  84. ^ Devilbiss DM, Waterhouse BD. Norepinephrine exhibits two distinct profiles of action on sensory cortical neuron responses to excitatory synaptic stimuli. Synapse. (2000)
  85. ^ Chikvaidze VN, Nikuradze VO. The role of adrenoreceptors in the mechanism of pharmacological action of cavinton. Ukr Biokhim Zh. (1987)
  86. ^ a b c d e Trejo F, Nekrassov V, Sitges M. Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings. Brain Res. (2001)
  87. ^ a b c d e Sitges M, et al. Characterization of phenytoin, carbamazepine, vinpocetine and clorgyline simultaneous effects on sodium channels and catecholamine metabolism in rat striatal nerve endings. Neurochem Res. (2009)
  88. ^ Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci. (1999)
  89. ^ a b c d e Kiss B, Cai NS, Erdö SL. Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies. Eur J Pharmacol. (1991)
  90. ^ a b c Westphalen RI, Stadlin A. Dopamine uptake blockers nullify methamphetamine-induced decrease in dopamine uptake and plasma membrane potential in rat striatal synaptosomes. Ann N Y Acad Sci. (2000)
  91. ^ a b Herrera-Mundo N, Sitges M. Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings. J Neurochem. (2013)
  92. ^ Alexi T, et al. 3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration. Neuroreport. (1998)
  93. ^ Reynolds DS, Carter RJ, Morton AJ. Dopamine modulates the susceptibility of striatal neurons to 3-nitropropionic acid in the rat model of Huntington's disease. J Neurosci. (1998)
  94. ^ Villarán RF, et al. Endogenous dopamine enhances the neurotoxicity of 3-nitropropionic acid in the striatum through the increase of mitochondrial respiratory inhibition and free radicals production. Neurotoxicology. (2008)
  95. ^ Zaitone SA, Abo-Elmatty DM, Elshazly SM. Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats. Indian J Pharmacol. (2012)
  96. ^ Erdö SL, et al. Vinpocetin protects against excitotoxic cell death in primary cultures of rat cerebral cortex. Eur J Pharmacol. (1990)
  97. ^ Biró K, Kárpáti E, Szporny L. Protective activity of ethyl apovincaminate on ischaemic anoxia of the brain. Arzneimittelforschung. (1976)
  98. ^ King GA. Protective effects of vinpocetine and structurally related drugs on the lethal consequences of hypoxia in mice. Arch Int Pharmacodyn Ther. (1987)
  99. ^ Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. (1988)
  100. ^ Kaneko S, et al. Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and 3HMK-801 binding. Eur J Pharmacol. (1991)
  101. ^ a b c Sitges M, Galván E, Nekrassov V. Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes. Neurochem Int. (2005)
  102. ^ a b c 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. (2006)
  103. ^ Sitges M, et al. Effects of carbamazepine, phenytoin, lamotrigine, oxcarbazepine, topiramate and vinpocetine on Na+ channel-mediated release of {3H}glutamate in hippocampal nerve endings. Neuropharmacology. (2007)
  104. ^ Sitges M, Guarneros A, Nekrassov V. Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of {3H}glutamate: comparison with the Na+ channel-mediated release. Neuropharmacology. (2007)
  105. ^ Tapia R, Sitges M. Effect of 4-aminopyridine on transmitter release in synaptosomes. Brain Res. (1982)
  106. ^ Galván E, Sitges M. Characterization of the participation of sodium channels on the rise in Na+ induced by 4-aminopyridine (4-AP) in synaptosomes. Neurochem Res. (2004)
  107. ^ Nekrassov V, Sitges M. Comparison of acute, chronic and post-treatment effects of carbamazepine and vinpocetine on hearing loss and seizures induced by 4-aminopyridine. Clin Neurophysiol. (2008)
  108. ^ a b Sitges M, et al. Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs. Epilepsy Res. (2011)
  109. ^ Nekrassov V, Sitges M. Vinpocetine inhibits the epileptic cortical activity and auditory alterations induced by pentylenetetrazole in the guinea pig in vivo. Epilepsy Res. (2004)
  110. ^ a b Sitges M, Nekrassov V. Vinpocetine prevents 4-aminopyridine-induced changes in the EEG, the auditory brainstem responses and hearing. Clin Neurophysiol. (2004)
  111. ^ Braestrup C, Squires RF. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci U S A. (1977)
  112. ^ Gulyás B, et al. {11C}vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies. J Neurol Sci. (2005)
  113. ^ Banati RB. Visualising microglial activation in vivo. Glia. (2002)
  114. ^ Kassiou M, Meikle SR, Banati RB. Ligands for peripheral benzodiazepine binding sites in glial cells. Brain Res Brain Res Rev. (2005)
  115. ^ a b Gulyás B, et al. Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker {((11))C}vinpocetine. J Neurol Sci. (2012)
  116. ^ Lang S. The role of peripheral benzodiazepine receptors (PBRs) in CNS pathophysiology. Curr Med Chem. (2002)
  117. ^ Papadopoulos V. Peripheral benzodiazepine receptor: structure and function in health and disease. Ann Pharm Fr. (2003)
  118. ^ a b c Chen MK, Guilarte TR. Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther. (2008)
  119. ^ Medina AE. Vinpocetine as a potent antiinflammatory agent. Proc Natl Acad Sci U S A. (2010)
  120. ^ a b Zhao YY, et al. TSPO-specific ligand Vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation. Neuron Glia Biol. (2011)
  121. ^ Mouton PR, et al. Age and gender effects on microglia and astrocyte numbers in brains of mice. Brain Res. (2002)
  122. ^ Peters A. Structural changes in the normally aging cerebral cortex of primates. Prog Brain Res. (2002)
  123. ^ Batarseh A, Papadopoulos V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. (2010)
  124. ^ Gulyás B, et al. Age and disease related changes in the translocator protein (TSPO) system in the human brain: positron emission tomography measurements with {11C}vinpocetine. Neuroimage. (2011)
  125. ^ Venneti S, Lopresti BJ, Wiley CA. The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol. (2006)
  126. ^ Papadopoulos V, Lecanu L. Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma. Exp Neurol. (2009)
  127. ^ a b Cai Y, Li JD, Yan C. Vinpocetine attenuates lipid accumulation and atherosclerosis formation. Biochem Biophys Res Commun. (2013)
  128. ^ Chen J, et al. Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein e/endothelial nitric oxide synthase double knockout mice. Circulation. (2001)
  129. ^ Mitra S, Goyal T, Mehta JL. Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther. (2011)
  130. ^ a b c d e Kim D, et al. Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation. (2001)
  131. ^ Sata M, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. (2002)
  132. ^ Torsney E, Xu Q. Resident vascular progenitor cells. J Mol Cell Cardiol. (2011)
  133. ^ a b Cai Y, et al. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration. J Pharmacol Exp Ther. (2012)
  134. ^ Sundaresan M, et al. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. (1995)
  135. ^ Abdel Salam OM, Oraby FH, Hassan NS. Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats. Acta Biol Hung. (2007)
  136. ^ Nekrassov V, Sitges M. Vinpocetine protects from aminoglycoside antibiotic-induced hearing loss in guinea pig in vivo. Brain Res. (2000)
  137. ^ Huang EW, et al. Vinpocetine inhibits breast cancer cells growth in vitro and in vivo. Apoptosis. (2012)
  138. ^ Münzel T, et al. Dissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery disease. J Am Coll Cardiol. (1996)
  139. ^ Münzel T, Daiber A, Gori T. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. (2011)
  140. ^ Feil R, Kleppisch T. NO/cGMP-dependent modulation of synaptic transmission. Handb Exp Pharmacol. (2008)
  141. ^ Sonnenburg WK, et al. Identification of inhibitory and calmodulin-binding domains of the PDE1A1 and PDE1A2 calmodulin-stimulated cyclic nucleotide phosphodiesterases. J Biol Chem. (1995)
  142. ^ Sharma RK, Wang JH. Differential regulation of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isoenzymes by cyclic AMP-dependent protein kinase and calmodulin-dependent phosphatase. Proc Natl Acad Sci U S A. (1985)
  143. ^ Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation.
  144. ^ Hutter K, Deli L, Csomós I. {Successful resuscitation from sudden death caused by Cavinton}. Orv Hetil. (1980)
  145. ^ Dany F, et al. {Cardiac toxicity of vincamine: a seven cases report of ventricular arrhythmias by parenteral administration of vincamine (author's transl)}. Therapie. (1981)
  146. ^ van Hecke E. Contact sensitivity to vincamine tartrate. Contact Dermatitis. (1981)
  147. ^ Agranulocytosis Induced By Vinpocetine.
  148. ^ Svirbely JL, Szent-Györgyi A. Prenatal Developmental Toxicity Studies Of Vinpocetine In Sprague Dawley (Hsd:Sprague Dawley SD) Rats And New Zealand White (Hra:NZW SPF) Rabbits. Biochem J. (1932)
  149. ^ Waidyanatha S, et al. Systemic exposure of vinpocetine in pregnant Sprague Dawley rats following repeated oral exposure: An investigation of fetal transfer. Toxicol Appl Pharmacol. (2018)
  150. Lim CC, Cook PJ, James IM. The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers. Br J Clin Pharmacol. (1980)
  151. Vorob'eva OV, Tamarova ES. Efficacy of vinpotropile in the therapy of initial signs of cerebrovascular pathology. Zh Nevrol Psikhiatr Im S S Korsakova. (2010)
  152. Zakharov VV. Vinpotropil in the treatment of dyscirculatory encephalopathy with cognitive impairment without dementia. Zh Nevrol Psikhiatr Im S S Korsakova. (2010)
  153. Chukanova EI. Efficacy of cavinton in the treatment of patients with chronic blood flow insufficiency. Russian multicenter clinical-epidemiological program "CALIPSO". Zh Nevrol Psikhiatr Im S S Korsakova. (2010)