Vinpocetine

Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus.
Gaál L, Molnár P.
Eur J Pharmacol. 1990 Oct 23;187(3):537-9.

 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. PMID: 2073927

  Vinpocetine effects on cognitive impairments produced by flunitrazepam.
Bhatti JZ, Hindmarch I.
Int Clin Psychopharmacol. 1987 Oct;2(4):325-31.

 The effects of pre-treatment with vinpocetine 40 mg, on flunitrazepam-induced impairment of memory, were studied in 8 normal volunteers. Tests of Critical Flicker Fusion Threshold, a Sternberg Memory Scanning Task, along with subjective ratings of drug action were used. Drug effects were found to be modest. Treatment with vinpocetine was associated with improvements in short-term memory processes. PMID: 3693872

  The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies.
Bagoly E, Fehér G, Szapáry L.
Orv Hetil. 2007 Jul 22;148(29):1353-8.

 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. 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. 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 O2 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. 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.
PMID: 17631470

  Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons.
Tárnok K, Kiss E, Luiten PG, Nyakas C, Tihanyi K, Schlett K, Eisel UL.
Neurochem Int. 2008 Dec;53(6-8):289-95

 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. PMID: 18793690