Vinpocetine

Abstract: Background Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. Objectives To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias. Search methods The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 23 March 2009 using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. This register contains up to date references from major health care databases like MEDLINE and EMBASE as well as records from trials databases in the field of dementia.The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian). Selection criteria All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded. Data collection and analysis Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest and the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1). Main results All identified studies were performed before and in the early 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30 mg/day and 60 mg/day compared with placebo, but the number of patients treated for six months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. Authors' conclusions Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Abstract: Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways These factors may explain the common side effects and the limited clinical efficacy of these compounds Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders We investigated the role of PDEs in human detrusor smooth muscle Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro In addition, initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only This might be due to the rather low dosage chosen and the small sample size Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population Modulation of intracellular key enzymes effecting second messenger metabolism, ie isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction

Abstract: The efficacy and tolerance of orally administered vinpocetine was investigated in patients suffering from mild to moderate organic psychosyndromes including primary dementia. Two hundred and three patients were included in a placebo-controlled, randomized double-blind, multicentre trial and received every day for 16 weeks either: 3 x 10 mg doses of vinpocetine, 3 x 20 mg doses of vinpocetine, or 3 x placebo. Patients were assessed on ratings of clinical global impression, cognitive performance and on measures of the quality of life including depressive illness. There were no clinically relevant side-effects reported and the frequencies of adverse events between patients treated with vinpocetine (30 mg or 60 mg) and placebo were comparable. Statistically significant improvements were found in favour of both active treatment groups compared to placebo in both confirmatory evaluations of efficacy of treatment: the "Global Improvement" (on the CGI scale) and cognitive performance (SKT). Vinpocetine was also superior to placebo in ratings of the "severity of illness". This study demonstrates the usefulness and efficacy of vinpocetine in the management of patients with moderate organic psychosyndromes. An apparently greater therapeutic efficacy of 3 x 10 mg vinpocetine compared with the higher vinpocetine dosage is statistically not significant.