Vinpocetine
References:Psychopharmacological effects of vinpocetine in normal healthy volunteers.Z. Subhan and I. Hindmarch. European Journal of Clinical Pharmacology, 1985, Vol. 28, Num. 5, Pages 567-571.
Abstract: Twelve healthy female volunteers received pre-treatments with vinpocetine 10, 20, 40 mg and placebo (t.d.s.) for two days according to a randomised, double-blind crossover design. On the third day of treatment and 1 h following morning dosage, subjects completed a battery of psychological tests including Ciritcal Flicker Fusion (CFF), Choice Reaction Time (CRT), Subjective Ratings of Drug Effects (LARS) and a Sternberg Memory Scanning Test. No statistically significant changes from placebo were observed on CFF, CRT or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was found to be significantly improved following treatment with vinpocetine 40 mg when compared to placebo and results suggested a localised effect of the drug on the serial comparison stage of the reaction process.
Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. DeNoble VJ, Repetti SJ, Gelpke LW, Wood LM, Keim KL. Pharmacol Biochem Behav. 1986 Apr;24(4):1123-8.
Abstract:Vinpocetine, vincamine, aniracetam, and Hydergine, compounds with purported cognition activating activity, were evaluated for their ability to prevent scopolamine-induced and hypoxia-induced impairment of passive avoidance retention (24 hr) in rats. Vinpocetine (peak effect dose [PED]= 200 mg/kg PO), aniracetam (PED = 100 mg/kg PO), vincamine (PED = 30 mg/kg PO), and Hydergine (PED = 1 mg/kg PO) prevented memory disruption by scopolamine. Vinpocetine (PED = 3 mg/kg PO) and aniracetam (PED = 30 mg/kg PO) were also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen hypoxia. In contrast, Hydergine (0.05 to 3 mg/kg PO) and vincamine (0.3 to 100 mg/kg PO) were not effective against hypoxia-induced impairment. Hydergine at doses greater than 10 mg/kg PO markedly impaired motor function. In both tests the protection was dose-related for all test substances in an inverted U-shaped manner. Mecamylamine (1, 3, 10 mg/kg SC), (-)-nicotine (0.1 to 0.4 mg/kg SC), apovincaminic acid (1-400 mg/kg PO) and pemoline (1-100 mg/kg PO) did not protect against memory impairment induced by either procedure. These data support the view that vinpocetine, a compound chemically distinct from the pyrrolidinones, has a cognitive activating ability as defined in models of both scopolamine-induced and hypoxia-induced memory impairment in rats.
Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. John Polich, Rebecca Gloria. Human Psychopharmacology: Clinical and Experimental. Volume 16, Issue 5 , Pages 409 - 416.
Abstract: A computerized test battery was used in a double-blind design to assess the cognitive effects of a nutrient compound containing Ginkgo biloba in 24 normal adults. Ten tasks (perceptual, attention and short-term memory) were presented in a standardized manner designed to maximize performance, with substantial pre-test practice employed to minimize response variability. Subjects were given either placebo or Ginkgo biloba extract capsules to consume for 14 days, after which they performed all tasks twice. They then received the other condition, and after 14 days completed the final test session. Response time and error rate stabilized after pre-test practice. A working memory capacity paradigm demonstrated a reliable 50 ms response time decrease between the placebo and Ginkgo biloba testing, suggesting that Ginkgo biloba speeds short-term working memory processing in normal adults.
Possible memory-enhancing properties of vinpocetine. Donna M. Coleston, Ian Hindmarch. Drug Development Research 2004 Oct; 14(3-4):191-193.
Abstract: Critical flicker fusion threshold, choice reaction time, total reaction time, and Sternbergtype memory tasks of digits/words were measured in twelve volunteers after having received vinpocetine or placebo for two days. A significant improvement was recorded in the short-term memory test following 40 mg of the drug when compared to placebo.
A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. Balestreri R, Fontana L, Astengo F. J Am Geriatr Soc. 1987 May;35(5):425-30.
Abstract: In a double-blind clinical trial, vinpocetine, a synthetic ethyl ester of apovincamine, was shown to effect significant improvement in elderly patients with chronic cerebral dysfunction. Forty-two patients received 10 mg vinpocetine three times a day (tid) for 30 days, then 5 mg tid for 60 days. Matching placebo tablets were given to another 42 patients for the 90 day trial period. Patients on vinpocetine scored consistently better in all evaluations of the effectiveness of treatment including measurements on the Clinical Global Impression (CGI) scale, the Sandoz Clinical Assessment-Geriatric (SCAG) scale, and the Mini-Mental Status Questionnaire (MMSQ). There were no serious side effects related to the treatment drug.
Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine. The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease . Hadjiev D. Ideggyogy Sz. 2003; 56(5-6):166-72
Abstract: The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease. It is also known as latent insufficiency of the cerebrovascular circulation or as asymptomatic cerebrovascular disorders. Recently, the term subclinical disease, detected noninvasively, has been introduced by American Heart Association. The diagnosis is based on the following criteria: evidence of vascular risk factors; episodic nonspecific complaints without any focal cerebral symptoms; mild cognitive deficit, detected by neuropsychological tests; carotid ultrasonography often shows intimal-medial thickening, atherosclerotic plaques and carotid stenosis; CT and MRI occasionally reveal silent cerebral infarctions, white matter hyperintensities or cerebral atrophy; regional hypoperfusion above the ischemic threshold is also seen by rCBF measurements. Treatment of the AICVD, modifying the vascular risk factors and using neuroprotective agents, should be the cornerstone of primary prevention of ischemic stroke and cognitive decline, caused by cerebrovascular disorders. Vinpocetine has been found to interfere with various stages of the ischemic cascade: ATP depletion, activation of voltage-sensitive Na(+)- and Ca(++)-channels, glutamate and free radicals release. The inhibition of the voltage-sensitive Na(+)-channels appears to be especially relevant to the neuroprotective effect of vinpocetine. Pronounced antioxidant activity of the drug could also contribute to the neuroprotection. PET studies in primates and man showed that 11C labelled vinpocetine passes the blood-brain barrier rapidly. Heterogeneous brain distribution of the compound was observed mainly in the thalamus, basal ganglia, occipital, parietal and temporal cortex, regions which are closely related to the cognitive functions. PET studies in chronic ischemic stroke patients revealed favourable effects of vinpocetine on rCBF and glucose metabolism in the thalamus, basal ganglia and primary visual cortex. It seems, vinpocetine, affecting the multiple mechanisms of the AICVD, could be of benefit for the treatment in this early stage of cerebrovascular disease. Vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.
Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Nicholson CD. Psychopharmacology (Berl). 1990; 101(2):147-59
Abstract: The development of effective drugs for the treatment of dementia is an important therapeutic target. Drugs which stop the progression of dementia have not been developed; however, nootropics and metabolically active compounds such as the vinca alkaloids and the ergot alkaloids as well as alkylxanthines are widely used to alleviate the symptoms. This review summarises animal studies investigating the mechanism of action of these compounds and highlights gaps in our knowledge of their pharmacology. Nootropics, such as piracetam, facilitate learning and retrieval of information and protect the brain from physical and chemical intoxication. Nootropics may produce these effects via an enhancement of acetylcholine or dopamine release; however, this postulate requires further evaluation. The pharmacology of vinca alkaloids is reviewed with particular reference to vinpocetine. This compound attenuates cognitive deficits, reduces ischaemia-induced hippocampal cell loss and increases cerebral blood flow and glucose utilisation. These effects may be induced by modulation of cyclic nucleotide levels and adenosine re-uptake inhibition. An extensively examined ergot alkaloid is co-dergocrine; this compound increases both the oxygen tension and the electrical activity of the ischaemic cerebral cortex. Alkylxanthines have a wide range of pharmacological activities, and in this review the pharmacology of pentoxifylline, propentofylline and denbufylline is contrasted with that of theophylline and caffeine. In particular, the pharmacology of propentofylline and the selective low Km cyclic AMP phosphodiesterase inhibitor denbufylline is summarised. Although more carefully controlled clinical trials in well defined patient collectives are required, present evidence suggests some therapeutic efficacy for nootropics and metabolically active compounds.
A vinca alkaloid enhances morphological dynamics of dendritic spines of neocortical layer 2/3 pyramidal cells. Brain Res Bull. 2003 Jan 15;59(4):257-60. Lendvai B, Zelles T, Rozsa B, Vizi ES.
Abstract: We imaged neocortical layer 2/3 pyramidal cells in rat brain slices with two-photon laser scanning microscopy to investigate that spine motility can be influenced by the voltage-dependent Na(+) and Ca(2+) channel inhibitor, vinpocetine, which exhibited positive cognitive effects in human studies. Veratridine, which enhances sodium influx, was also tested on dendritic spine motility. Perfusion with vinpocetine, a derivative of vinca alkaloids, caused a substantial increase in the structural dynamics of dendritic spines measured by the changes in length or the number of new/retracted spines. In contrast, enhancement of sodium influx with veratridine failed to change spine motility. Our results indicate that the rapid changes in spine shape and size could occur, when calcium and sodium influx has been decreased by this vinca alkaloid. Spine motility induced by vinpocetine may be associated to microtubule alterations, an effect that was described for other vinca alkaloids. On the other hand, the potential of vinpocetine to enhance cognition in clinical studies suggests that the increased spine motility may be related to cognitive functions.
In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Horvath, Beata : Marton, Zsolt : Halmosi, Robert : Alexy, Tamas : Szapary, Laszlo : Vekasi, Judit : Biro, Zsolt : Habon, Tamas : Kesmarky, Gabor : Toth, Kalman. Clin-Neuropharmacol. 2002 Jan-Feb; 25(1): 37-42
Abstract: Oxygen-free radicals play an important role in several physiologic and pathophysiologic processes. In pathologic circumstances, they can modify and damage biologic systems. Because oxygen-free radicals are involved in a wide range of diseases (cerebrovascular, cardiovascular, etc.), scavenging these radicals should be considered as an important therapeutic approach. In our in vitro study, we investigated the antioxidant capacity of three drugs: pentoxiphylline (Sigma Aldrich, St. Louis, MO, USA) piracetam (Sigma Aldrich), and vinpocetine (Richter Gedeon RT, Budapest, Hungary). Phenazine methosulphate was applied to generate free radicals, increasing red blood cell rigidity. Filtration technique and potassium leaking were used to detect the cellular damage and the scavenging effect of the examined drugs. According to our results, at human therapeutic serum concentration, only vinpocetine (Richter Gedeon RT) had significant (p less than 0.01) scavenging activity with a protective effect that increased further at higher concentrations. Pentoxiphylline (Sigma Aldrich) and piracetam (Sigma Aldrich) did not have significant antioxidant capacity at therapeutic concentrations, but increasing their concentrations (pentoxiphylline at 100-times, and piracetam at 10-times higher concentrations) led to a significant (p less than 0.01) scavenger effect. Our findings suggest that this pronounced antioxidant effect of vinpocetine and even the milder scavenging capacity of pentoxiphylline and piracetam may be of value in the treatment of patients with cerebrovascular disorders, but merits further investigations.
The nootropic drug vinpocetine inhibits veratridine-induced [Ca2+]i increase in rat hippocampal CA1 pyramidal cells. Zelles, T : Franklin, L : Koncz, I : Lendvai, B : Zsilla, G. Neurochem-Res. 2001 Sep; 26(8-9): 1095-100
Abstract: The alkaloid derivative vinpocetine (14-ethoxycarbonyl-(3alpha,16alpha-ethyl)-14,15-eburnamine; Cavinton) has a well known beneficial effect on brain function in hypoxic and ischemic conditions. While it increases CNS blood flow and improves cellular metabolism, relatively little is known about vinpocetine's underlying molecular mechanisms on the single cell level. Since apoptotic and necrotic cell damage is always preceded by an increase in [Ca2+]i, this study investigated the effect of vinpocetine on [Ca2+]i increases in acute brain slices. Sodium influx is an early event in the biochemical cascade that takes place during ischemia. The alkaloid veratridine can activate this Na+ influx, causing depolarization and increasing [Ca2+]i in the cells. Therefore, it can be used to simulate an ischemic attack in brain cells. Using a cooled CCD camera-based ratio imaging system and cell loading with fura 2/AM, the effect of vinpocetine on [Ca2+]i changes in single pyramidal neurons in the vulnerable CA1 region of rat hippocampal slices was investigated. Preperfusion and continuous administration of vinpocetine (10 microM) significantly inhibited the elevation in [Ca2+]i induced by veratridine (10 microM). When the drug was administered after veratridine, it could accelerate the recovery of cellular calcium levels. Piracetam, another nootropic used in clinical practice, could attenuate the elevation of [Ca2+]i only at a high, 1 mM, concentration. We have concluded that vinpocetine, at a pharmacologically relevant concentration, can decrease pathologically high [Ca2+]i levels in individual rat hippocampal CA1 pyramidal neurons; this effect might contribute to the neuroprotective property of the drug.
Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells. Pereira, C : Agostinho, P : Oliveira, C R. Free-Radic-Res. 2000 Nov; 33(5): 497-506
Abstract: The cytoprotective effect of vinpocetine [14-ethoxycarbonyl-(3alpha, 16alpha-ethyl)-14,15-eburnamine] was investigated on PC12 cells treated with the amyloid beta-peptides (Abeta) for 24 hours. Vinpocetine was shown to protect cells from the inhibition in redox status induced by exposure to Abeta25-35 and Abeta1-40, the maximal protection being achieved at a vinpocetine concentration of 40 microM. At this concentration, vinpocetine blocked the inhibition of the mitochondrial respiratory chain complexes II-III and IV and completely abolished the depletion of pyruvate levels induced by toxic concentrations of Abeta peptides. Furthermore, the accumulation of ROS in cells exposed to Abeta25-35 and Abeta1-40 evaluated using the fluorescent probe 2',7'-dichlorofluorescin (DCF), was reduced in the presence of 40 microM vinpocetine. Taken together, the data presented herein demonstrate that vinpocetine protects cells from Abeta toxicity, preventing the generation of oxidative stress due to the excessive accumulation of ROS. This study suggests that vinpocetine can exert neuroprotective properties which might be of importance and contribute to its clinical efficacy in the treatment of Alzheimer's disease.
Synaptosomal response to oxidative stress: effect of vinpocetine. Santos , M S : Duarte, A I : Moreira, P I : Oliveira, C R. Free-Radic-Res. 2000 Jan; 32(1): 57-66
Abstract: It has been suggested that reactive oxygen species (ROS) play a role in the neuronal damage occurring in ischemic injury and neurodegenerative disorders and that their neutralization by antioxidant drugs may delay or minimize neurodegeneration. In the present study we examine whether vinpocetine can act as an antioxidant and prevent the formation of ROS and lipid peroxidation in rat brain synaptosomes. After ascorbate/Fe2+ treatment a significant increase in oxygen consumption (about 5-fold) and thiobarbituric acid reactive substances (TBARS) formation (about 7-fold) occurred as compared to control conditions. Vinpocetine inhibited the ascorbate/Fe2+ stimulated consumption of oxygen and TBARS accumulation, an indicator of lipid peroxidation, in a concentration-dependent manner. The ROS formation was also prevented by vinpocetine. Oxidative stress increased significantly the fluorescence of the probes 2',7'-dichlorodihydrofluorescein (DCFH2-DA) (about 6-fold) and dihydrorhodamine (DHR) 123 (about 10-fold), which is indicative of intrasynaptosomal ROS generation. Vinpocetine at 100 microM concentration decreased the fluorescence of DCFH2-DA and DHR 123 by about 50% and 83%, respectively. We conclude that the antioxidant effect of vinpocetine might contribute to the protective role exerted by the drug in reducing neuronal damage in pathological situations.
The neuroprotective drug vinpocetine prevents veratridine-induced [Na+]i and [Ca2+]i rise in synaptosomes. Tretter, L : Adam Vizi, V. Neuroreport. 1998 Jun 1; 9(8): 1849-53
Abstract: The effect of the neuroprotective drug, vinpocetine on the veratridine-evoked [Na+]i and [Ca2+]i rise in isolated nerve terminals was studied. Vinpocetine, in a pharmacologically relevant concentration range (0.4-10 microM)i reduced the increase of [Na+]i induced by veratridine (100 microM). The effect of the drug was concentration-dependent with 10 microM vinpocetine completely preventing the increase of [Na+]i. The [Ca2+]i rise in response to veratridine was also prevented by vinpocetine. In addition, the [Ca2+]i signal induced by depolarization with 20 mM K+ was reduced by vinpocetine (1-20 microM). This effect was not influenced by preincubation with 1 microM TTX and was also observed when Na+ was replaced by N-methyl glucamine in the medium. It is concluded that vinpocetine is capable of inhibiting voltage-dependent Na+ and Ca2+ channels, respectively, and these effects might contribute to the neuroprotection exerted by the drug.
Comparative efficacy of vinpocetine, pentoxifylline and nicergoline on red blood cell deformability. Hayakawa, M. Arzneimittelforschung. 1992 Feb; 42(2): 108-10
Abstract: Using two different filtration methods for evaluating red blood cell deformability, the comparative effects of single oral doses of vinpocetine (CAS 42971-09-5; 10 mg), pentoxifylline (300 mg) and nicergoline (20 mg) were evaluated in 5 healthy volunteers. Out of the three agents only vinpocetine appeared to increase red blood cell deformability significantly. Thus vinpocetine was the most active drug tested and warrants further investigation in circulatory conditions characterized by a decrease in red cell deformability.
Effect of vinpocetine on red blood cell deformability in stroke patients. Hayakawa, M. Arzneimittelforschung. 1992 Apr; 42(4): 425-7
Abstract: Reduction in red blood cell deformability is a contributory factor in stroke disease, and it has been postulated that red blood cell rigidification may be improved by drug treatment. In this paper the effect of vinpocetine (CAS 42971-09-5) on the deformability of red blood cells from patients with chronic ischemic cerebrovascular disease has been examined. During the administration of vinpocetine for 3 months a significant improvement in red blood cell deformability was observed without adverse effect.
Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies . Kiss, B : Cai, N S : Erdo, S L. Eur-J-Pharmacol. 1991 Dec 10; 209(1-2): 109-12
Abstract: The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.
Protective effect of vinpocetine against brain damage caused by ischemia. Rischke, R : Krieglstein, J. Jpn-J-Pharmacol. 1991 Jul; 56(3): 349-56
Abstract: The effects of vinpocetine against hippocampal neuronal damage and on local cerebral blood flow (LCBF) were examined in a rat model of forebrain ischemia (10-min occlusion of the carotid arteries and hypotension). Histological evaluation of neuronal loss in the hippocampus was performed 7 days after ischemia. LCBF was measured before ischemia as well as after 2 min and 1 hr of recirculation. Vinpocetine (10 mg/kg) administered pre- or post-ischemically reduced the hippocampal neuronal necrosis, while pre-ischemic administration of 2 or 20 mg/kg vinpocetine was ineffective. Since vinpocetine increased the LCBF after 1 hr of recirculation, it cannot be excluded that blood flow improvements contribute to its neuroprotective activity. On the other hand, there is no clear evidence that an elevation of post-ischemic hypoperfusion could protect neurons against ischemic damage. It is, therefore, suggested that vinpocetine acts directly on brain cells.
Influence of vinpocetine on warfarin-induced inhibition of coagulation. Hitzenberger, G : Sommer, W : Grandt, R. Int-J-Clin-Pharmacol-Ther-Toxicol. 1990 Aug; 28(8): 323-8
Abstract: The influence of 14 days of concomitant vinpocetine administration on prothrombin time prolongation of single 25 mg doses of warfarin was investigated. Eighteen male subjects were included in the study. They received 25 mg warfarin the first day. Prothrombin time, warfarin plasma levels and factor VII coagulation time were monitored on days 1-5. Ten mg vinpocetine was administered from day 6 to 24. Another single dose of 25 mg of warfarin was given a second time on day 20. AUC values of prothrombin time, warfarin plasma level and factor VII clotting time curves and appropriate Cmax and tmax plasma levels of days 20-24 were compared with those of days 1-5. The confidence interval limits of the ratio of AUC20-24/AUC1-5 of prothrombin time curves were within the limits of 0.8 and 1.2, so that the formal criteria of equivalent biological activity were met. However, a minute influence probably without clinical implication is likely since both point estimate as well as confidence interval limits were below 1.
Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type . Tohgi, H : Sasaki, K : Chiba, K : Nozaki, Y. Arzneimittelforschung. 1990 Jun; 40(6): 640-3
Abstract: Oxygen affinity of hemoglobin, erythrocyte 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentrations were compared before and after oral administration of vinpocetine (TCV-3B) (15 mg/d), a primarily vasodilating agent, for three weeks in eight patients with vascular dementia of the Biswanger type which is characterized by diffuse myelin pallor and multiple lacunes in the cerebral white matter. After vinpocetine administration, oxygen affinity of hemoglobin (P50) was significantly increased (26.5 +/- 0.55 to 27.6 +/- 0.62 mmHg; mean and standard deviation, p less than 0.05), red blood cell (RBC) ATP concentrations were significantly increased (846 +/- 168 to 1,158 +/- 130 mumol/l RBC, p less than 0.05), while DPG concentrations were unaltered (4.46 +/- 0.48 to 4.59 +/- 0.57 mmol/l RBC). There was a significant positive correlation between the increase of P50 and the increase of erythrocyte ATP concentrations (r = 0.67, p less than 0.05). The effect of vinpocetine of enhancing oxygen release of hemoglobin may offer an additional benefit to its primary vasodilating action in the treatment of vascular dementia of the Binswanger type due to chronic ischemia.
Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidney of rabbits with experimental atherosclerosis: preventive effects of vinpocetine on the deposition of these elements . Yasui, M : Yano, I : Ota, K : Oshima, A. J-Int-Med-Res. 1990 Mar-Apr; 18(2): 142-52
Abstract: Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidneys were determined in 16 rabbits with atherosclerosis experimentally induced by a cholesterol-rich diet and the protective effect of 3 or 10 mg/kg.day vinpocetine (14-ethoxycarbonyl-(3 alpha,16 alpha-ethyl)-14,15-eburnamenine) given orally on the deposition of these elements was assessed. Rabbits fed a cholesterol-rich diet developed atherosclerosis after 3 months and these rabbits possessed high concentrations of calcium, phosphorus and aluminium in the central nervous system, determined by neutron activation analysis. In atherosclerotic rabbits fed a vinpocetine supplement, there was a decrease in concentrations of these elements in tissues. It is suggested that calcium, phosphorus and aluminium may be implicated in the aetiology of atherosclerosis and that vinpocetine may have a preventive action
Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus. Gaal, L : Molnar, P. Eur-J-Pharmacol. 1990 Oct 23; 187(3): 537-9
Abstract: Conventional extracellular single unit recordings were used to investigate the effect of vinpocetine on locus coeruleus noradrenergic neurons in chloral hydrate-anesthetized rats. Vinpocetine produced a significant and dose-dependent increase in the firing rate of locus coeruleus neurons (ED30 = 0.75 mg/kg i.v.) up to 1 mg/kg i.v., followed by a complete blockade of spiking activity at doses higher than this. The effective dose range was in very good agreement with the dose range corresponding to the memory-enhancing effects of the compound. Our results supplied direct electrophysiological evidence that vinpocetine increases the activity of ascending noradrenergic pathways. This effect can be related to the cognitive-enhancing characteristics of the compound.
Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a near infrared spectroscopy and transcranial Doppler study. Bonoczk, Peter : Panczel, Gyula : Nagy, Zoltan. Eur-J-Ultrasound. 2002 Jun; 15(1-2): 85-91
Abstract: To investigate the effect of vinpocetine on cerebral blood flow (CBF) in the compromised circulation of a stroke affected hemisphere using transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) methods. METHODS: 43 patients with ischemic stroke were randomized into vinpocetine (VP) and placebo group in a double blind, placebo-controlled study of the effect of a single-dose i.v. infusion of vinpocetine on cerebral blood perfusion and oxygenation. In the VP group 20 mg VP in 500 ml saline, in the placebo group 500 ml saline alone were administered. The concentrations of oxy-, reduced- and total hemoglobin were measured by NIRS frontolaterally on the side of lesion while the mean cerebral blood flow velocity (CBFV), the pulsatility index (PI) and Doppler spectral intensity (DSI) were monitored by TCD in the middle cerebral artery on the same side. Values were averaged for the first 5 min prior to the infusion and for the last 5 min of infusion and they were compared between groups. RESULTS: The concentration of all three chromophores increased during infusion in the VP group (mean dHbT = 1.03, CI(95) = 0.84, P = 0.058; mean dHbO = 0.92, CI(95) = 0.91, P = 0.071; mean dHb = 0.10, CI(95) = 0.21, P = 0.297). The HbT and HbO showed a substantially smaller increase in the placebo group (mean dHbT = 0.31, CI(95) = 0.74, P = 0.22; mean dHbO = 0.57, CI(95) = 0.80, P = 0.094) while the Hb decreased (mean dHb = -0.26, CI(95) = 0.29, P = 0.05). Comparing to the placebo group Hb increased significantly in the VP group (P = 0.027) while the increase of HbO and HbT did not reach the level of significance (P = 0.29 and 0.11). DSI showed a significantly larger increase in the VP than in placebo group (dDSI=25.8 CI(95)=8.8 [VP]; dDSI =3.3, CI(95) = 3.7 [Placebo], P < 0.005). The CBFV and PI did not differ significantly between groups. (dVm = 5.0+/-2.98 cm/s [VP], dVm = 4.1+/-2.57 cm/s [Placebo], P = 0.28; dPI = 0.08 [VP], dPI = 0.09 [Placebo]; P = 0.47). CONCLUSION: VP increases cerebral perfusion and parenchymal oxygen extraction as well. The increased perfusion was indicated by NIRS and by TCD measurement of DSI while conventional velocity and pulsatility measurements failed to detect theses effects. NIRS is a sensitive, feasible method of measuring changes in regional blood flow and tissue oxygenation in the superficial cortex.
Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements Yasui M; Yano I; Ota K; Oshima A No To Shinkei. 1990; 42(4):325-31
Abstract: The aims in this study were designed to clarify the contents of calcium (Ca), phosphorus (P) and aluminum (Al) in central nervous system (CNS), liver and kidney of rabbits with atherosclerosis experimentally induced by cholesterol-rich diet, and investigate scavenger effect of 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine) on the deposition of these elements in CNS and soft tissues of experimental atherosclerosis. Sixteen male rabbits were divided into 4 groups. Each group was fed with standard diet (Group A), standard diet containing 1.5% cholesterol (Group B), standard diet containing 1.5% cholesterol plus oral administration of 3 mg/kg/day vinpocetine (Group C), and standard diet containing 1.5% cholesterol plus administration of 10 mg/kg/day vinpocetine (Group D). After 3 months' feeding, experimental atherosclerosis was produced with a modified method of Kritchevsky et al in rabbits of Groups B, C and D. Blood was collected by cardiocentesis under the anesthesia of ether and then rabbits sacrificed to remove CNS and other tissues. The blood was stood for 1 hour at room temperature and separated by centrifugation at 3000 rpm for 10 min to determine serum total cholesterol, phospholipids, HDL-cholesterol, peroxide lipid, NEFA and calcium levels. Ca, P and Al contents in the frontal lobe, pons, cerebellum, spinal cord, liver and kidney were determined by neutron activation analysis. Ca contents of CNS, liver and kidney in Group B significantly increased than those of Group A (p less than 0.01), and significantly decreased in Groups C and D compared with those of Group B (p less than 0.01).
Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation . Gabryel, B : Adamek, M : Pudelko, A : Malecki, A : Trzeciak, H I Neurotoxicology. 2002 May; 23(1): 19-31
Abstract: The aim of the present study was to establish whether piracetam (2-pyrrolidon-N-acetamide; PIR) and vinpocetine (a vasoactive vinca alkaloid; VINP) are capable of protecting astrocytes against hypoxic injury. Using the model of astrocyte cell culture we observed the cells treated with PIR and VINP during and after in vitro simulated hypoxia. Cell viability was determined by Live/Dead Viability/Cytotoxicity Assay Kit, LDH release assay and MTT conversion test. Apoptotic cell death was distinguished by a method of Hoechst 33342 staining underfluorescence microscope and caspase-3 colorimetric assay. In addition the intracellular levels of ATP and phosphocreatine (PCr) were evaluated by bioluminescence method. Moreover, the effect of the drugs on the DNA synthesis was evaluated by measuring the incorporation of [3H]thymidine into DNA of astrocytes. PIR (0.01 and 1 mM) and VINP (0.1 and 10 microM) were added to the medium both during 24 h normoxia, 24 h hypoxia or 24 h reoxygenation. Administration of 1 mM PIR or 0.1 microM VINP to the cultures during hypoxia significantly decreases the number of dead and apoptotic cells. The antiapoptic effects of drugs in the above mentioned concentrations was also confirmed by their stimulation of mitochondrial function, the increase of intracellular ATP, and the inhibition of the caspase-3 activity. The prevention of apoptosis was accompanied by the increase in ATP and PCr levels and increase in the proliferation of astrocytes exposed to reoxygenation. The higher concentration of VINP (10 microM) was detrimental in hypoxic conditions. Our experiment proved the significant cytoprotective effect of 1 mM PIR and 0.1 microM VINP on astrocytes in vitro.