|AHFS/Drugs.com||International Drug Names|
|Bioavailability||56.6 +/- 8.9%|
|Elimination half-life||2.54 +/- 0.48 hours|
|Chemical and physical data|
|Molar mass||350.454 g/mol|
|3D model (JSmol)|
|(what is this?)|
Vinpocetine (brand names: Cavinton, Intelectol; chemical name: ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine (sometimes described as "a synthetic ethyl ester of apovincamine"), an extract from the lesser periwinkle plant. Vinpocetine was first isolated from the plant in 1975 by the Hungarian chemist Csaba Szántay. The mass production of the synthetic compound was started in 1978 by the Hungarian pharmaceutical company Richter Gedeon.
Vinpocetine has been clinically used in many countries for treatment of cerebrovascular disorders such as stroke and dementia for more than 30 years. Due to its excellent safety profile, increasing efforts have been put into exploring the novel therapeutic effects and mechanism of actions of vinpocetine in various cell types and disease models. Recent studies have revealed a number of novel functions of vinpocetine, including anti-inflammation, antagonizing injury-induced vascular remodeling and high-fat-diet-induced atherosclerosis, as well as attenuating pathological cardiac remodeling. These novel findings may facilitate the repositioning of vinpocetine for preventing or treating relevant disorders in humans.
Vinpocetine is not FDA approved in the United States for therapeutic use. The U.S. Food & Drug Administration (FDA) has ruled that vinpocetine, due to its synthetic nature and proposed therapeutic uses, was ineligible to be marketed as dietary supplement under the Federal Food, Drug, and Cosmetic Act (FDCA).
Controlled clinical trials
In vitro, animal, and human studies
Kindling models in rats has shown vinpocetine to exhibit anticonvulsant properties. The most pronounced anticonvulsant effects were observed in Pentylenetetrazole (PTZ)-kindled rats although there was also an effect on amygdala-kindled and neocortically-kindled rats. Vinpocetine has also been shown to abolish [3H]Glu release after in vivo exposure to 4-aminopyridine (4-AP) which suggests an important mechanism for vinpocetine anticonvulsant activity.
Vinpocetine has been investigated in animal models as a potential anti-inflammatory agent. Vinpocetine inhibits the up-regulation of NF-κB by TNFα in various cell tests. Reverse transcription polymerase chain reaction also shows that it reduced the TNFα-induced expression of the mRNA of proinflammatory molecules such as interleukin-1 beta, monocyte chemoattractant protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1). In mice, vinpocetine reduced lipopolysaccharide inoculation induced polymorphonuclear neutrophil infiltration into the lung.
Another study looked at cerebral circulation and intellectual impairment found a correlation between aging brain and intellectual impairment suggesting its clinical efficacy in improving intellectual impairment in patients with aging brain.
In Acute Ischemic Stroke Patients Vinpocetine Inhibited NF-κB-Dependent Inflammation patients treated with vinpocetine had a better recovery of neurological function and improved clinical outcomes during the acute phase and at 3-month follow-up. These findings identify vinpocetine as an inflammation modulator that could improve clinical outcomes after acute ischemic stroke.
Mechanism of action
Vinpocetine acts as a phosphodiesterase (PDE) type-1 inhibitor in isolated rabbit aorta, Independent of vinpocetine's action on PDE, vinpocetine inhibits IKK preventing IκB degradation and the following translocation of NF-κB to the cell nucleus.
Increases in neuronal levels of DOPAC, a metabolic breakdown product of dopamine, have been shown to occur in striatal isolated nerve endings as a result of exposure to vinpocetine which may upregulate dopamine receptors. Such an effect is consistent with the biogenic pharmacology of reserpine, a structural relative of vinpocetine. However, this effect tends to be reversible upon cessation of vinpocetine administration, with full remission typically occurring within 3–4 weeks.
Some studies have noted flushing, rashes, or minor gastrointestinal problems in some subjects; however, these side effects did not warrant discontinuation of the medication. Some users have reported headaches, especially at doses above 15 milligrams per day, as well as occasional upset stomach. The safety of vinpocetine in pregnant women has not been evaluated. Vinpocetine has been implicated in one case to induce agranulocytosis,[unreliable medical source?] a serious condition in which granulocytes are markedly decreased. Some people have anecdotally noted that their continued use of vinpocetine reduces immune function. Commission E warned that vinpocetine reduced immune function could cause apoptosis (cellular death) in the long term.
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