Cavinton scientific update |
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2010 May 25;107(21):9795-800. Epub 2010 May 6.
Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon DS, Abe J, Berk BC, Li JD, Yan C.
Aab Cardiovascular Research Institute and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Vinopocetine showcases NF-kappaB-dependent inflammation with an IKK-dependent
Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism
Inflammation is a hallmark of many diseases, such as atherosclerosis, chronic obstructive pulmonary disease, arthritis, infectious diseases, and cancer. Although steroids and cyclooxygenase inhibitors are effective antiinflammatory therapeutical agents, they may cause serious side effects. Therefore, developing unique antiinflammatory agents without significant adverse effects is urgently needed. Vinpocetine, a derivative of the alkaloid vincamine, has long been used for cerebrovascular disorders and cognitive impairment. Its role in inhibiting inflammation, however, remains unexplored. Here, we show that vinpocetine acts as an antiinflammatory agent in vitro and in vivo. In particular, vinpocetine inhibits TNF-alpha-induced NF-kappaB activation and the subsequent induction of proinflammatory mediators in multiple cell types, including vascular smooth muscle cells, endothelial cells, macrophages, and epithelial cells. We also show that vinpocetine inhibits monocyte adhesion and chemotaxis, which are critical processes during inflammation. Moreover, vinpocetine potently inhibits TNF-alpha- or LPS-induced up-regulation of proinflammatory mediators, including TNF-alpha, IL-1beta, and macrophage inflammatory protein-2, and decreases interstitial infiltration of polymorphonuclear leukocytes in a mouse model of TNF-alpha- or LPS-induced lung inflammation. Interestingly, vinpocetine inhibits NF-kappaB-dependent inflammatory responses by directly targeting IKK, independent of its well-known inhibitory effects on phosphodiesterase and Ca(2+) regulation. These studies thus identify vinpocetine as a unique antiinflammatory agent that may be repositioned for the treatment of many inflammatory diseases.
2010 Jul 15;878(22):1959-66. Epub 2010 Jun 1.
Xia HM, Su LN, Guo JW, Liu GM, Pang ZQ, Jiang XG, Chen J.
Department of Pharmaceutics, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai 201203, PR China.
Experiments conducted on rats reveals functions of vinpocetine and its initials metabolism
Determination of vinpocetine and its primary metabolite, apovincaminic acid, in rat plasma by liquid chromatography-tandem mass spectrometry
A precise and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of vinpocetine (VP) and its primary metabolite, apovincaminic acid (AVA), in rat plasma was developed and validated. The analytes and the internal standard-dimenhydrinate were extracted from 50 microL aliquots of rat plasma via solid-liquid extraction. Chromatographic separation was achieved in a run time of 3.5 min on a C(18) column under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for VP, AVA and IS were m/z 351.4-->280.2, 323.2-->280.2 and 256.2-->167.3 respectively. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect, stability study and dilution integrity. A linear dynamic range of 0.5-500 ng/mL for both VP and AVA was evaluated with mean correlation coefficient (r) of 0.9970 and 0.9984 respectively. The precision of the assay (RSD%) was less than 8.55% at all concentrations levels for both VP and AVA. This method was successfully applied to a pharmacokinetic study of VP in rats after intravenous (1 mg/kg) and oral (1 mg/kg) administration. 2010 Elsevier B.V. All rights reserved.
2010 Apr;46(4):265-77.
Vohora D, Saraogi P, Yazdani MA, Bhowmik M, Khanam R, Pillai KK.
Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Strategic advances in adjacent therapies for epilepsy
Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs.
Voltage-gated sodium channel blockers like phenytoin and carbamazepine have long been used in the treatment of epilepsy. Brain sodium channels continue to be an important target of many newer second-generation (fosphenytoin, oxcarbazepine, lamotrigine, felbamate, topiramate, zonisamide) and third-generation (eslicarbazepine, brivaracetam, carisbamate, fluorofelbamate, elpetrigine, lacosamide, rufinamide, safinamide, vinpocetine) antiepileptic drugs (AEDs). Some of the newer drugs show either state-dependent antiepileptic action or sodium channel subtype selectivity, although most agents do not differentiate between these channel subtypes. The present review highlights the preclinical and clinical efficacy, pharmacokinetics, drug interactions and adverse event profiles. It also addresses AED selection of sodium channel blockers that constitutes the third generation of AEDs. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.
2009;43(3):223-32.
Muravyov AV, Tikhomirova IA, Maimistova AA, Bulaeva SV.
Department of Medicine and Biology, University of Yaroslavl, 150000 Yaroslavl, Russia.
Availability of signaling pathways under red blood cell aggregation and physical deformity changes
Extra- and intracellular signaling pathways under red blood cell aggregation and deformability changes.
Exposure of red blood cells (RBCs) to catecholamines (epinephrine, phenylephrine, an agonist of alpha1-adrenergic receptors, clonidine, an agonist of alpha2-adrenergic receptors and isoproterenol, an agonist of beta-adrenergic receptors) led to change in the RBC microrheological properties. When forskolin (10 microM), an AC stimulator was added to RBC suspension, the RBC deformability (RBCD) was increased by 17% (p<0.05). Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP (by 27%; p<0.01). Red blood cell aggregation (RBCA) was significantly decreased under these conditions (p<0.01). All drugs having PDE activity increased red cell deformability similarly. Some more changes of deformability was found after RBC incubation with pentoxifylline--25% (p<0.05) and IBMX incubation was accompanied only by 15% rise of RBC deformability. The drugs with PDE inhibitory activity reduced red cell aggregation. The most significant RBCA reduction effect was found under cell incubation with pentoxifylline and inhibitor PDE1-vinpocetine. On the whole RBCA reduction averaged 36% (p<0.05) under RBCs incubation with PDE inhibitors. The rise of Ca2+ influx, stimulated by A23187, was accompanied by an increase of RBCA, whereas red cell deformability was changed insignificantly. At the same time Ca2+ entry blocking into the red cells by verapamil or its chelating in medium by EGTA led to significant RBCA decrease and deformability rise (p<0.05).On the whole the total data clearly show that the red cell aggregation and deformation changes were connected with an activation of the different intracellular signaling pathways. It seems reasonable to suppose that RBCA decrease was mainly associated with an activation of the adenylyl-cyclase-cAMP system, while the red cell deformability was closely associated with Ca2+ control mechanisms.
2009 Oct 12;620(1-3):49-56. Epub 2009 Aug 21.
Deshmukh R, Sharma V, Mehan S, Sharma N, Bedi KL.
Division of Neuropharmacology, Department of Pharmacology, ISF College of Pharmacy, Punjab, India.
Amalgam of intracerebroventricular streptozotocin instigated by cognitive multi function and oxidated stress by vinpocetine
Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine -- a PDE1 inhibitor.
Enhancing cyclic nucleotides signaling by inhibition of phosphodiesterases (PDEs) is known to be beneficial in disorders associated with cognitive decline. The present study was designed to investigate the effect of vinpocetine (PDE1 inhibitor) on intracerebroventricular (i.c.v.) streptozotocin induced experimental sporadic dementia of Alzheimer's type. Infusion of streptozotocin impaired learning and memory, increased oxidative-nitritive stress and induced cholinergic hypofunction in rats. Chronic treatment with vinpocetine (5, 10 and 20 mg/kg i.p.) for 21 days following first i.c.v. streptozotocin infusion significantly improved learning and memory in Morris water maze and passive avoidance paradigms. Further, vinpocetine significantly reduced the oxidative-nitritive stress, as evidenced by decrease in malondialdehyde (MDA) and nitrite levels, and restored the reduced glutathione (GSH) levels. Significant increase in acetylcholinesterase activity and lactate dehydrogenase levels was observed in the present model indicating cholinergic hypofunction and increase in neuronal cell damage. Chronic treatment with vinpocetine also reduced significantly the increase in acetylcholinesterase activity and lactate dehydrogenase levels indicating restorative capacity of vinpocetine with respect to cholinergic functions and preventing the neuronal damage. The observed beneficial effects of vinpocetine on spatial memory may be due to its ability to favorably modulate cholinergic functions, prevent neuronal cell damage and possibly through its antioxidant mechanism also.
2009 Sep-Oct;55(5):635-42.
Vishnevskiĭ AA, Korotkevich IG, Zhaparalieva ChO.
Relevance and functions of vinpocetine when conducted experiments on rats with cerebral ischemia
Membrane and functional effects of vinpocetine and tocopherol in rats with experimental cerebral ischemia
The membrane, antioxidant and functional effects of vinpocetine and a-tocopherol have been investigated under conditions of acute experimental cerebral ischemia in rats. Vinpocetine administration decreased accumulation of lysophospholipids in brain plasma membranes. Vinpocetine also blocked accumulation of conjugated dienes (CD). alpha-Tocopherol inhibited augmentation in CD content and did not reduce the level of lysophospholipids in brain plasma membranes. Functional consequences of membrane impairments were also detected in some behavioral tests and physical capabilities. Administration of both vinpocetine and alpha-tocopherol decreased manifestations of the altered parameters induced by cerebral ischemia and vinpocetine was more effective than alpha-tocopherol.
2008 Dec;53(6-8):289-95. Epub 2008 Aug 28.
Tárnok K, Kiss E, Luiten PG, Nyakas C, Tihanyi K, Schlett K, Eisel UL.
Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons
Functions of vinpocetine and neuroprotection in primary cortical neurons
Vinpocetine (ethyl apovincaminate), a synthetic derivative of the Vinca minor alkaloid vincamine, is widely used for the treatment of cerebrovascular-related diseases. One of the proposed mechanisms underlying its action is to protect against the cytotoxic effects of glutamate overexposure. Glutamate excitotoxicity leads to the disregulation of mitochondrial function and neuronal metabolism. As Vinpocetine has a binding affinity to the peripheral-type benzodiazepine receptor (PBR) involved in the mitochondrial transition pore complex, we investigated whether neuroprotection can be at least partially due to Vinpocetine's effects on PBRs. Neuroprotective effects of PK11195 and Ro5-4864, two drugs with selective and high affinity to PBR, were compared to Vinpocetine in glutamate excitotoxicity assays on primary cortical neuronal cultures. Vinpocetine exerted a neuroprotective action in a 1-50microM concentration range while PK11195 and Ro5-4864 were only slightly neuroprotective, especially in high (>25microM) concentrations. Combined pretreatment of neuronal cultures with Vinpocetine and PK11195 or Ro5-4864 showed increased neuroprotection in a dose-dependent manner, indicating that the different drugs may have different targets. To test this hypothesis, mitochondrial membrane potential (MMP) of cultured neurons was measured by flow cytometry. 25microM Vinpocetine reduced the decrease of mitochondrial inner membrane potential induced by glutamate exposure, but Ro5-4864 in itself was found to be more potent to block glutamate-evoked changes in MMP. Combination of Ro5-4864 and Vinpocetine treatment was found to be even more effective. In summary, the present results indicate that the neuroprotective action of vinpocetine in culture can not be explained by its effect on neuronal PBRs alone and that additional drug targets are involved.
2008 Sep;326(3):889-96. Epub 2008 Jun 12.
Kita K, Takahashi K, Ohashi Y, Takasuka H, Aihara E, Takeuchi K.
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Phosphodiesterase isozymes inclusive of regulating secretion of an alternative in an alien rat stomach vitro
Phosphodiesterase isozymes involved in regulation of formula secretion in isolated mouse stomach in vitro
(+/-)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide] (NOR-3), a nitric-oxide (NO) donor, is known to increase HCO(3)(-) secretion in rat stomachs, intracellularly mediated by cGMP; yet, there is no information about the phosphodiesterase (PDE) isozyme involved in this process. We examined the effects of various isozyme-selective PDE inhibitors on the secretion of HCO(3)(-) in the mouse stomach in vitro and the type(s) of PDE isozymes involved in the response to NO. The gastric mucosa of DDY mice was stripped of the muscle layer and mounted on an Ussing chamber. HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. NOR-3, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), and various PDE inhibitors were added to the serosal side. Vinpocetine (PDE1 inhibitor) or zaprinast (PDE5 inhibitor) was also added serosally 30 min before NOR-3 or 8-Br-cGMP. Both NOR-3 and 8-Br-cGMP stimulated HCO(3)(-) secretion in a dose-dependent manner, and the response to NOR-3 was significantly inhibited by methylene blue. Likewise, the secretion induced by NOR-3 or 8-Br-cGMP was significantly attenuated by 6-((2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo(2.2.2)octan-2-yl)-5Z-hexenoic acid (ONO-8711), the PGE receptor (EP)1 antagonist, as well as indomethacin and potentiated by both vinpocetine and zaprinast at doses that had no effect by themselves on the basal secretion, whereas other subtype-selective PDE inhibitors had no effect. NOR-3 increased the mucosal PGE(2) content in a methylene blue-inhibitable manner. These results suggest that NO stimulates gastric HCO(3)(-) secretion mediated intracellularly by cGMP and modified by both PDE1 and PDE5, and this response is finally mediated by endogenous PGE(2) via the activation of EP1 receptors.
2008 Jun;56(6):796-801.
Li J, Chen F, Hu C, He L, Yan K, Zhou L, Pan W.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Minimised preparation required for the adultery delivery of vinpocetine
Optimized preparation of in situ forming microparticles for the parenteral delivery of vinpocetine
A spherical symmetric design-response surface methodology was applied to optimize the preparation of vinpocetine-loaded poly(D,L-lactide-co-glycolide) PLGA in situ forming microparticles (ISM system). The influence of the ratio of PLGA to vinpocetine (w/w), the concentration of Tween 80 (w/v) and the volume of propylene glycol on the burst release, medium particle diameter and size distribution was evaluated. Scan electron microscopy of the optimized in situ microparticles exhibited spherical shape, and vinpocetine-loading mainly inside the microparticles. The data showed that the release of vinpocetine from in situ microparticles in vitro and in vivo lasted about 40 d. In vivo pharmacokinetic characteristics of the optimized in situ microparticles was assessed after they were intramuscularly injected into rats. HPLC method was used to determine the plasma concentration of vinpocetine. The absolute bioavailability of vinpocetine in the microparticles was 27.6% in rats, which suggested that PLGA in situ microparticles were a valuable system for the delivery of vinpocetine.
2007;47(12):20-3.
Nevzorova VA, Zakharchuk NV, Plotnikova IV.
Level of cerebral blood flow in hypertensive crises and bridging its aspects for correction status
The state of cerebral blood flow in hypertensive crises and possibilities of its correction
We examined 60 patients with arterial hypertension admitted to hospital during hypertensive crisis. Control group consisted of 30 patients with normal arterial pressure. We investigated parameters of cerebral blood flow with the method of transcranial dopplerography, content of NO and a row of cytokines (interleukin-6, interleukin-0, tumor necrosis factor) in blood serum during hypotensive therapy with inclusion of calcium antagonist amlodipine and cerebroprotector vinpocetine. After 12 weeks of hypotensive therapy we noted significant antihypertensive effect, improvement of parameters of cerebral blood flow, and elevation of NO content in all groups of studied persons most pronounced in patients receiving amlodipine as monotherapy or in combination with vinpocetine. Administration of vinpocetine in addition to hypotensive therapy is justified in patients with hypertensive disease, as this significantly improves blood flow in cerebral vessels. This appears as elevation of linear blood flow velocity, lowering of peripheral resistance and increase of content of NO in blood serum.
2007 Jul;70(1):185-9.
Uckert S, Bazrafshan S, Scheller F, Mayer ME, Jonas U, Stief CG.
Department of Urology, Hannover Medical School, Hannover, Germany.
Relevant responses of alienated human seminal vesicle tissues to selected phosphodiesterase inhibitors
Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors
OBJECTIVES: To further elucidate the significance of the cyclic nucleotide-mediated signal transduction, we examined the in vitro functional responses of isolated seminal vesicle (SV) smooth muscle tissue to selective phosphodiesterase (PDE) inhibitors. METHODS: Using the organ bath technique, the effects of increasing concentrations (1 nM to 10 microM) of the PDE inhibitors vinpocetine (PDE1 inhibitor), rolipram (PDE4 inhibitor), and sildenafil and vardenafil (PDE5 inhibitors) on the tension induced by 10 microM of norepinephrine on SV tissue strips were investigated. To examine the drug effects on the tissue levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the SV strips were exposed to different concentrations of the compounds (0.1, 1, and 10 microM). After freezing, homogenization, and extraction of cyclic nucleotides, cAMP and cGMP were measured using radioimmunoassays. In the experiments, sodium nitroprusside and forskolin were used as reference compounds. RESULTS: The norepinephrine-induced tension was reversed by the drugs in a dose-dependent manner. The rank order of efficacy was rolipram greater than sildenafil greater than vardenafil greater than or equal to vinpocetine greater than sodium nitroprusside greater than forskolin. The reversion of the norepinephrine-induced tension at maximum drug concentration ranged from 79% (rolipram) to 32% (forskolin). Only rolipram and sildenafil reached a median effective concentration. The effects of the PDE inhibitors were paralleled by a 1.7-fold to 173-fold increase in tissue cGMP or cAMP. CONCLUSIONS: Our results have demonstrated that PDE inhibitors can reverse the adrenergic tension of human SV tissue and increase levels of cyclic nucleotides. This outlines the potential significance of cAMP and cGMP in the control of SV smooth muscle function. These findings might be of importance with regard to the pharmacologic treatment of premature ejaculation.
Biomed Khim. 2009 Sep-Oct;55(5):635-42.
Vishnevskiĭ AA, Korotkevich IG, Zhaparalieva ChO.
Membrane and functional effects of vinpocetine and tocopherol in rats with experimental cerebral ischemia
The membrane, antioxidant and functional effects of vinpocetine and a-tocopherol have been investigated under conditions of acute experimental cerebral ischemia in rats. Vinpocetine administration decreased accumulation of lysophospholipids in brain plasma membranes. Vinpocetine also blocked accumulation of conjugated dienes (CD). alpha-Tocopherol inhibited augmentation in CD content and did not reduce the level of lysophospholipids in brain plasma membranes. Functional consequences of membrane impairments were also detected in some behavioral tests and physical capabilities. Administration of both vinpocetine and alpha-tocopherol decreased manifestations of the altered parameters induced by cerebral ischemia and vinpocetine was more effective than alpha-tocopherol.
Vestn Otorinolaringol. 2009;(6):69-70.
Afon'kin VIu, Dobretsov KG, Sipkin AV.
Vestn Otorinolaringol.
The new scheme of cavinton application to the treatment of chronic neurosensory loss of hearing
The objective of this study was to evaluate results of the new therapeutic modality for the management of chronic neurosensory loss of hearing based on the use of caviton. The open randomized study involved 50 patients. Criteria for the efficiency of therapy included the patients' complaints, self-evaluation of tympanophonia based on the visual-analogous scale, results of audiologic examination and Doppler ultrasound of carotid and vertebral arteries. Significant improvement of audiologic characteristics was documented in 80% of the patients; ultrasound examination showed that most of them tended to benefit from caviton therapy and reported reduction of tympanophonia. It is concluded that the new caviton dosing scheme for the treatment of neurosecretory loss of hearing is well tolerated by the patients and can be recommended for more extensive clinical application.
Orv Hetil. 2007 Jul 22;148(29):1353-8.
Bagoly E, Fehér G, Szapáry L.
Pécsi Tudományegyetem, Altalános Orvostudományi Kar Neurológiai Klinika Pécs Rét u 2 7623.
[The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies] [Article in Hungarian]
Importance of vinpocetine for curing cerebrovascular diseases with respect to human case studies
INTRODUCTION: It shows the importance of cerebrovascular diseases that they are the third main cause of death exceeded only by coronary artery diseases and cancer. Cerebral ischemia leads to irreversible brain damage, thereby it is important to rescue the hypoperfused areas. Patients without stroke but with chronic cerebral hypoperfusion can also benefit from the increasing of the cerebral blood flow. METHODS: The aim of this review was to summarize the indications and the potential effects of vinpocetine in acute and chronic cerebrovascular diseases based on clinical studies. RESULTS: There is no evidence that vinpocetine treatment is applicable in acute ischemic stroke, only few study with low patient number showed a slight but significant improvement in the patients conditions. In chronic cerebrovascular patients after single dose and long-term vinpocetine therapy, PET, TCD, SPECT and NIRS examinations showed increasing perfusion and elevated glucose and O 2 consumption of the examined areas, furthermore significant improvement of the rheologic factors was detected. A meta-analysis of international clinical studies showed a significant improvement in cognitive achievement in chronic stroke patients after oral therapy. CONCLUSION: The cited studies showed the potential multi-pharmacological effects of vinpocetine and its beneficial hemorheological potential. The drug also improves the blood flow and the metabolism of the affected brain areas. There is increasing evidence that vinpocetine improves the quality of life in chronic cerebrovascular patients.
Ideggyogy Sz. 2007 Jul 30;60(7-8):301-10.
Valikovics A.
Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház, Neurológia-Toxikológia-Stroke Osztály, Miskolc.
[Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions] [Article in Hungarian]
INTRODUCTION: Vinpocetine has been widely used in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. Chronic cerebral hypoperfusion plays an important role in the development of certain types of dementia. In consequence of complex mode of action vinpocetine plays a significant role in the improvement of cerebral hypoperfusion. The symptoms of mild cognitive impairment considered as "predementia" are similar to those of dementia, although milder. AIMS: The authors investigated the characteristics of the blood flow parameters of patients with ischemic stroke and mild cognitive impairment both in resting conditions or following chemical stimulus as well as they investigated the severity of mental deterioration in the two patient groups. In a pilot study the authors examined the influence of 12-week long oral vinpocetine therapy on the blood flow parameters and cognitive functions in the two patient groups. METHODS: The authors studied the blood flow velocity of a. cerebri media in resting conditions and after 30 sec of breath holding with transcranial Doppler before treatment and after a 12-week long oral vinpocetine treatment. At the same time psychometric tests (MMSE, ADAS-Cog) were used in order to examine cognitive functions, while the general condition of the patients were scored by Clinical Global Impression (CGI) scale. RESULTS: After a 12-week long oral vinpocetine treatment the increase of blood flow velocity in resting conditions compared to the baseline values was significant in the vascular group. The percent increase of mean velocity after the breath holding TCD test showed a significant increase compared to the baseline in both patient groups. The authors found a significant improvement of cognitive functions after a 12-week long oral vinpocetine therapy using psychometric tests. The improvement was identical in both groups. The general condition of patients improved significantly according to both the investigator's and the patients' opinion; patients with mild cognitive impairment judged the improvement higher. CONCLUSIONS: Vinpocetine improved the cerebrovascular reserve capacity in both patient groups and favourably influenced the cognitive status and general condition of patients with chronic hypoperfusion. The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.
Biol Pharm Bull. 2008 Jan;31(1):118-25.
Chen Y, Li G, Wu X, Chen Z, Hang J, Qin B, Chen S, Wang R.
Department of Pharmacy, Wuhan General Hospital, Wuhan 430070, P. R. China
Self-microemulsifying drug delivery system (SMEDDS) of vinpocetine: formulation development and in vivo assessment.
A new self-microemulsifying drug delivery system (SMEDDS) has been developed to increase the solubility, dissolution rate and oral bioavailability of vinpocetine (VIP), a poor water-soluble drug. The formulations of VIP-SMEDDS were optimized by solubility assay, compatibility tests, and pseudo-ternary phase diagrams analysis. The optimal ratio in the formulation of SMEDDS was found to be Labrafac : oleic acid : Cremophor EL : Transcutol P=40 : 10 : 40 : 10 (w/w). The average particle diameter of VIP was less than 50 nm. In vitro dissolution study indicated that the dialysis method in reverse was better than the ultrafiltration method and the dialysis method in simulating the drug in vivo environment. Comparing with VIP crude drug power and commercial tablets, (-)VIP-SMEDDS caused a 3.4- and 2.9-fold increase in the percent of accumulated dissolution at 3 h. Further study on the absorption property of VIP-SMEDDS employing in situ intestine of rats demonstrated that VIP in SMEDDS could be well-absorbed in general intestinal tract without specific absorption sites. In addition, the developed SMEDDS formulations significantly improved the oral bioavailability of VIP in rats. Relative bioavailability of (-)VIP-SMEDDS and (+)VIP-SMEDDS increased by 1.85- and 1.91-fold, respectively, in relative of VIP crude powder suspension. The mechanisms of enhanced bioavailability of VIP might contribute to the improved release, enhanced lymphatic transport, and increased intestinal permeability of the drug.
Zh Nevrol Psikhiatr Im S S Korsakova. 2006;Suppl 16:46-50.
Vaizova OE, Vengerovskiĭ AI, Alifirova VM.
[An effect of vinpocetine (cavinton) on endothelium function in patients with chronic cerebral ischemia] [Article in Russian]
The influence of vinpocetine (cavinton) on endothelium function in 87 patients with chronic cerebral ischemia has been studied. Vinpocetine exerts an endothelium protective effect which appears as a partial renewal of endothelium-dependent vasodilatation and inhibition of rejection of Willebrand factor during arteriovenous occlusion test. Leveling of neurological deficit by vinpocetine depends on the extent of renewal of endothelium-dependent vasodilatation.
Phytomedicine. 2009 Mar;16(2-3):111-7.
Feher G, Koltai K, Kesmarky G, Horvath B, Toth K, Komoly S, Szapary L.
Department of Neurology, University of Pecs School of Medicine, H-7623 Pecs, Ret u. 2, Hungary.
Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases.
INTRODUCTION: Hemorheological factors play an important role in the pathomechanism of ischemic cerebrovascular disorders. Abnormal rheological conditions in patients with chronic cerebrovascular disease predispose for recurrent strokes. Vinpocetine (VP), a synthetic ethyl esther of apovincamine, has successfully been used in the treatment of cerebrovascular diseases, in part because of its favourable rheological effects. PATIENTS AND METHODS: The study investigates the hemorheological changes in 40 patients in the chronic stage of ischemic cardiovascular disease after administration of vinpocetine. All patients received a high dose of intravenous VP in doses gradually increased to l mg/kg/day. In addition, 20 patients (mean age: 61+/-8 years) received 30 mg VP orally for 3 months. The other 20 patients (mean age: 59+/-6 years), who received placebo tablets, served as controls. Hemorheological parameters (hematocrit, plasma fibrinogen, whole blood viscosity, red blood cell aggregation and deformability) were evaluated at 1 and 3 months. RESULTS: The high-dose parenteral VP significantly decreased red blood cell aggregation, plasma and whole blood viscosity (p < 0.05) compared to the initial values. In patients with additional oral treatment, plasma and whole blood viscosities were significantly lower compared to the placebo patients at 3 months (p < 0.05). CONCLUSION: Our results confirmed the beneficial rheological effects of high-dose parenteral VP (partially caused by hemodilution) observed previously, and also warrant its long-term oral admission to maintain the beneficial rheological changes.
Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(9):35-39.
Chukanova EI.
Kafedra nevrologii i neĭrokhirurgii lechebnogo fakul'teta Rossiĭskogo gosudarstvennogo meditsinskogo universiteta, Moskva.
[Cavinton in the complex treatment of patients with chronic cerebrovascular insufficiency.] [Article in Russian]
A complex clinical-instrumental study included 138 patients with discirculatory encephalopathy (DE) who received cavinton perorally in dose 30 mg/day during 90 days (2 courses in a year) in addition to the basic therapy (hypotensive and antithrombotic drugs, neuroprotector glycine). A control group comprised 98 patients clinically matched with the main group. They received only basic therapy. Neurological status and results of neuropsychological tests were assessed before treatment and to the end of 3, 6 and 12 months. The improvement of all neurological syndromes studied was seen in the main group to the end of 12 months as compared to controls. The complex treatment using cavinton led to the significant decrease of risk of DE progression, development of transitory ischemic attacks and strokes compared to controls (relative risks were 0,01 and 0,14, respectively).
Orv Hetil. 2003 May 18;144(20):973-8.
Szapary L, Horvath B, Alexy T, Marton Z, Kesmarky G, Szots M, Nagy F, Czopf J, Toth K.
Pecsi Tudomanyegyetem, Altalanos Orvostudomanyi Kar, Neurologiai Klinika.
Effect of vinpocetin on the hemorheologic parameters in patients with chronic cerebrovascular disease.
How vinpocetin affect the hemorheologic parameters in cerebrovascular patients? Vinpocetine is widely used in the treatment of cerebrovascular diseases. High dose of parenteral vinpocetine treatment considerably reduce the hematocrit.
INTRODUCTION: Data collected from large number of multicenter, randomized trials in acute and chronic stroke patients provide evidence, that incidence and high mortality of cerebrovascular disorders can be decreased mainly by prevention and that the effectiveness of acute stroke treatment is limited. The terminology of "chronic cerebrovascular diseases" involves many pathologic entities and often atypical clinical symptoms refer to the focal or global hypoperfusion of the brain. However, hemorheological disturbances seem to be important factors of the complex pathomechanism. Vinpocetine has successfully been used in the treatment of cerebrovascular diseases, the part of the mechanism of action are the favourable rheological effects demonstrated after oral administration in more previous studies. AIMS AND METHODS: In this study the hemorheological changes after administration of small (30 mg/day) and high dose (increased to 70 mg/day) intravenous vinpocetine for 7 days in 30 patients in chronic phase of ischemic cerebrovascular disease were investigated. RESULTS: High dose parenteral vinpocetine treatment significantly (p < 0.05-0.005) decreased the hematocrit, the whole blood and plasma viscosity and red blood cell aggregation compared to the values before the treatment. Only red blood cell aggregation was improved significantly (p < 0.05) by small dose treatment. CONCLUSION: This study and other hemorheological studies in cerebrovascular patients demonstrated persistent rheological abnormalities despite the preventive therapy. The beneficial rheological effect of high dose parenteral vinpocetine indicates the use of this drug in the treatment of chronic cerebrovascular diseases.
Ideggyogy Sz. 2003 May 20;56(5-6):166-72.
Hadjiev D.
University Hospital of Neurology and Psychiatry, St. Naum Compl. Javorov, B-1504 Bulgaria, Sofia, bl. 21. A.
Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine.
The efficacy if vinpocetine in the treatment of ischemic cerebrovascular disorders. Vinpocetine affect the multiple mechanisms of the AICVD. This may become a benefit for the treatment in the early stage of cerebrovascular disease.
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.
Eur J Pharm Sci. 2005 Jan;24(1):1-13.
Ribeiro L, Carvalho RA, Ferreira DC, Veiga FJ.
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal.
Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies.
A research report on the multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers. This was monitored by NMR and solubility studies. It is found that sulfobutyl ether beta-cyclodextrin was more effective in vinpocetine solubilization.
This work deals with multicomponent complex formation of vinpocetine (VP) with beta-cyclodextrin (betaCD), sulfobutyl ether beta-cyclodextrin (SBEbetaCD) and tartaric acid (TA), in the presence or absence of water-soluble polymers, in aqueous solution. Complexation was monitored by phase-solubility and proton nuclear magnetic resonance ((1)H NMR) studies. TA demonstrated a synergistic effect on VP solubility, and in the complexation efficiency of betaCD and SBEbetaCD. Additionally, water-soluble polymers increased even more the complexation efficiency of the CDs that was reflected by a 2.1-2.5 increase on K(C) values for VP-CD-TA-polymer multicomponent complexes. SBEbetaCD was more effective in VP solubilization, as K(C) values of VP-SBEbetaCD-TA multicomponent complexes were notably higher than in corresponding betaCD complexes. The large chemical shift displacements from protons located in the interior of the hydrophobic CD cavities (i.e., H-3 and H-5) coupled with significant chemical shift displacements of VP aromatic protons suggested that this moiety was included in the cavity of both betaCD and SBEbetaCD. Two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments were carried out in order to obtain information about the multicomponent complex geometry in solution. Inspection of ROESY spectra allowed the establishment of spatial proximities between all aromatic protons of VP and the internal protons of the CDs, confirming that the aromatic moiety of VP is included in CD cavities being deeply inserted in SBEbetaCD multicomponent complexes, since additional interactions with the sulfobutyl side chains were evidenced.
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