Feigin VL, Doronin BM, Popova TF, Gribatcheva EV, Tchervov DV.

Department of Epidemiology and Preventive Medicine
Institute of Internal Medicine
Siberian Branch of the Russian Academy of Medical Science Novosibirsk, Russia.
v.feigin@ctru.auckland.ac.nz
Eur J Neurol 2001 Jan;8(1):81-5

Abstract

The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3–5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1–3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1–1.7). The National Institute of Health (NIH–NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted.

Szakall S, Boros I, Balkay L, Emri M, Fekete I, Kerenyi L, Lehel S, Marian T, Molnar T, Varga J, Galuska L, Tron L, Bereczki D, Csiba L, Gulyas B.

PET Centre,
Debrecen University Medical School, Hungary.
J Neuroimaging 1998 Oct;8(4):197-204

Abstract

The effects of vinpocetine on the cerebral glucose metabolism of chronic stroke patients are studied with positron emission tomography. The regional and global cerebral metabolic rates of glucose (CMRglu) and the kinetic constants related to them are quantified before and after single-dose intravenous vinpocetine treatment. These measurements are completed with transcranial Doppler sonography and single photon emission computed tomography to explore the possible mechanisms underlying the resulting changes in glucose uptake and metabolism in the brain. The authors’ findings indicate that a single-dose vinpocetine treatment, although it does not affect significantly the regional or global metabolic rates of glucose, improves significantly the transport of glucose (both uptake and release) through the blood-brain barrier in the whole brain, the entire contralateral hemisphere, and in the brain tissue around the infarct area of the symptomatic hemisphere. These changes are in accord with increased blood flow in the entire contralateral hemisphere as well as decreased blood flow velocity and increased peripheral vessel resistance in the entire symptomatic hemisphere.

Hayakawa M

Department of Geriatrics,
Nagoya University School of Medicine, Japan.
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 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.

Solti F, Iskum M, Czako E.

Arzneimittelforschung 1976;26(10a):1945-7

Abstract

The effect of ethyl apovincaminate (vinpocetine) on the cerebral and systemic circulations has been studied in detail in ten cases of cerebrovascular disease. 10 mg doses of vinpocetine were given as infusion within 4-6 min; circulatory tests were carried out prior to administration of the drug and 3-6 min after. The principal results showed the following: On vinpocetine cerebral vascular resistance was strongly reduced, while cerebral fraction of cardiac output significantly increased. On acute effect of the drug arterial mean pressure slightly decreased but cerebral blood flow nevertheless increased in general. Total vascular resistance also decreased but this decrease was less marked than that registered in cerebral vascular resistance.

Takeshi Shibuya & Katsuhiko Sato.

Department of Pharmacology,
Tokyo Medical College.
Igaku No Ayumi, 139, 3, 217-219

Abstract

We investigated the effect of vinpocetine on brain monoamines in rats with experimentally induced cerebral ischemia, using fluorescent histochemical techniques. The results indicate that 1) vinpocetine reversed the decreased brain tissue levels of catecholamines and serotonin following experimental cerebral ischemia; 2) the compound also facilitated the turnover of catecholamines and serotonin in the brain. These facts suggest that vinpocetine, with its proven actions to facilitate the turnover of rnonoamines in the brain and to improve impaired monoamine metabolism in experimental cerebral ischemia, might prove effective in augmenting cerebral blood flow.

Norihiko Tamaki M.D., Tadaki Kusunoki M.D., Satoshi Matsumoto M.D.

Department of Neurosurgery.
Kobe University School of Medicine.
Kobe, Japan
Advances in therapy 1985; 2:53-6

Abstract

The 133xenon inhalation method was used in an open-label clinical trial to examine changes in cerebral blood flow (CBF) after vinpocetine treatment in 13 patients with cerebrovascular disorders. In all patients, measurement of regional cerebral blood flow (RCBF) was made prior to and after treatment with vinpocetine 5 mg t.i.d. for five to seven weeks. In ten of the patients, treatment was continued for a total of 8 to 16 weeks with an additional RCBF measurement at the end of their treatment.
The results showed a significant increase in the Initial Slope Index (ISI) values of mean total CBF, and RCBF for the involved hemisphere after six weeks of treatment with vinpocetine. The CBF for the involved lobe was significantly increased for ISI and flow rate of gray matter at six weeks and at the end of treatment. No adverse reactions were reported.

Horvath B, Marton Z, Halmosi R, Alexy T, Szapary L,
Vekasi J, Biro Z, Habon T, Kesmarky G, Toth K.

First Department of Medicine
Division of Cardiology
University of Pecs’ School of Medicine, Pecs, Hungary.
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 < 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 < 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.

Marino Peruzza, M.D., Maurizio Dejacobis, M.D.

Uníversity of Pavia.
G.B. Glustinian Regional Hospital. Venice, Italy
Advances in therapy 1986; 4:201-4

Abstract

In a double-blind clinical trial, 22 elderly patients with cerebrovascular and central nervous system degenerative disorders were treated with vinpocetine, a synthetic ethyl ester of apovincamine. They received 10 mg vinpocetine t.i.d. for 30 days, then 5 mg t.i.d. for 60 days. Matching placebo tablets were given to another 20 elderly 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 Impressions
and Sandoz Clinical Assessment-Geriatric Seales and the Mini-Mental Status Questionnaire. No serious side effects were related to the treatment drug.

Gary A. King and Dolores Narcavage

Ayerst Laboratorias Research, Inc.,
CN 8000, Princeton, New Jersey
Drug Dev. Res. 9:225- 231,1986.

Abstract

Vinpocetine is an eburnamenine derivative reported to protect the brain from ischemia, both in experimental animals and in man. Its effects have been directly compared to those of vincamine, phenytoin, and cinnarizine in the Fisher rat following bilateral carotid artery occlusion (BCAO). Upon acute b.i.d. administration (25-100 rng/kg i.p.), both vinpocetine and vincamine significantly increased latency to ischemic convulsion in a dose-related manner, but neither drug significantly affected survival time. Neither phenytoin nor cinnarizine (25-100 mg/kg, b.i.d.) significantly altered latency to convulsions or survival time. After daily dosing for 5 days, vinpocetine, but none of the other drugs, caused a dose-related increase in the latency to ischemic convulsion. Vinpocetine’s effects occurred at lower doses (25 and 50 mg/kg/day) after subchronic administration than after acute administration. Vinpocetine (25 mg/kg/day) and cinnarizine (100 mg/kg/day) also increased survival time. These results are consistent with other experimental and clinical studies demonstrating a protective effect of vinpocetine against cerebral ischemia and further show that vinpocetine’s activity is maintained during repeated administration.

Manabu Miyazaki

Department of Internal Medicine,
Bell-land Hospital, Sakai City, Osaka, Japan
Drug Develop Res 1988; 14: 199-204

Abstract

The Doppler ultrasonic technique is useful for the examination of cerebral circulation as well as for the evaluation of cerebral circulation-improving drugs. This study deals with a correlation of cerebral circulation with intellectual impairment in subjects with aging brain syndrome and with measuring the effect of vinpocetine on cerebral circulation, using the Doppler technique.
The correlation between cerebral circulation and intellectual impairment was first studied in 48 patients with aging brain and intellectual impairment. As a parameter for cerebral circulation, the Continuous Index (CI), as calculated from the blood flow pattern recorded at the internal carotid artery, was used together with Hasegawa’s Dementia Scale (HDS) for intellectual impairment.
Second, blood flow change of the internal carotid and vertebral artery was measured after a single oral dose of 5 mg vinpocetine and after multiple oral doses of 5 mg vinpocetine three times daily for 7 days in six patients with aging brain.
The mean correlation coefficient (r) between CI and HDS was 0.391 (P < 0.01) in 48 patients. It was 0.612 (Fl < 0.01) in 27 patients with moderate to severe intellectual impairment, 0.735 (P < 0.01) in 14 patients with vascular type impairment, and 0.443 (not significant) in 10 patients with the Alzheimer type. The results suggest some correlation between cerebral circulation and intellectual impairment in the aging brain, especially in patients with the vascular type.
An increase of blood flow was recognizable after a single oral dose of 5 mg vinpocetine.