Disease relevance of Velnacrine

• The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients [1].
• THA and velnacrine were also tested in a rat hepatoma cell line (H4) and in primary dog hepatocytes [2].

Psychiatry related information on Velnacrine

• Effectiveness and safety of velnacrine for the treatment of Alzheimer's disease. A double-blind, placebo-controlled study. Mentane Study Group [3].
• To characterize this action further, the present study evaluated velnacrine for its ability to ameliorate the decline in short-term memory associated with aging in non-human primates at two time points after velnacrine administration: (1) 30 min and (2) 24 h [4].
• The present study assessed the safety and efficacy of the cholinesterase inhibitor, velnacrine, for treating the cognitive symptoms of Alzheimer's disease [5].
• OBJECTIVES: To determine the clinical efficacy and safety of velnacrine for patients with dementia of Alzheimer's type [6].

High impact information on Velnacrine

• 1. The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations [7].
• The production of NO by erythrocytes was measured with a commercial NO sensor during stimulation by L-arginine, acetylcholine, choline, atropine and velnacrine maleate (10 microM of final concentrations) [8].
• The results suggest that: (1) the position of the positive charge of tacrine may be important in the mechanism of its interaction with the membrane cytoskeleton; (2) like tacrine, velnacrine also strengthens cytoskeletal protein-protein interactions in erythrocyte membranes, but appears to be only about half as potent as tacrine [9].
• The structures of the metabolites 9-amino-1,2,3,4-tetrahydroacridin-1-ol (1-OH-THA), 9-amino-1,2,3,4-tetrahydroacridin-2-ol (2-OH-THA), and 9-amino-1,2,3,4-tetrahydroacridin-4-ol (4-OH-THA) were determined by electron impact mass spectrometry and/or 1H-NMR, and compared with synthetic references [10].
• Multiple dose pharmacokinetics, safety, and tolerance of velnacrine (HP 029) in healthy elderly subjects: a potential therapeutic agent for Alzheimer's disease [11].

Chemical compound and disease context of Velnacrine

• Variability in the plasma protein binding of velnacrine (1-hydroxy tacrine hydrochloride). A potential agent for Alzheimer's disease [12].
• Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD) [13].

Biological context of Velnacrine

• The effect of food on the bioavailability of velnacrine (HP 029) in healthy elderly men: a potential Alzheimer agent [14].
• OBJECTIVES: To quantify the protein binding of velnacrine in healthy individuals and investigate potential sources of variability [12].
• REVIEWERS' CONCLUSIONS: There has been no research into the use of velnacrine as a cognitive enhancer in the treatment of Alzheimer's disease since 1994 [6].

Anatomical context of Velnacrine

• Although velnacrine maleate has not been observed to cause prominent cytotoxicity in in vitro hepatocyte cultures, this drug was associated with elevated serum levels of hepatic enzymes in clinical trials [15].
• The effects of velnacrine on antipyrine metabolism in isolated rat hepatic microsomes were compared to those of cimetidine [16].

Associations of Velnacrine with other chemical compounds

• Standard solutions of human serum albumin and alpha 1 acid glycoprotein were incubated with velnacrine [12].

Gene context of Velnacrine

• With one acetylcholinesterase (AChE) inhibitor compound (velnacrine), we found that AD patients tolerated considerably lower dosages than young normals and healthy elderly subjects, whereas our findings were exactly the opposite with another AChE inhibitor (eptastigmine) [17].
• Both studies reported a significant benefit for velnacrine compared with placebo for the ADAS-cog, but the results could not be checked because the relevant information was not reported [6].

Analytical, diagnostic and therapeutic context of Velnacrine

• With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc-exametazime was shown with single photon emission computed tomography (SPECT) [1].
• In this open, randomized, crossover study, 24 healthy, elderly men were given 100 mg of velnacrine on two different study days to assess the influence of food on the bioavailability of velnacrine [14].
• Velnacrine was rapidly absorbed after oral administration [11].
• Plasma and urine concentrations of velnacrine were determined by an HPLC method [14].
• Determination of velnacrine in plasma and urine by high-performance liquid chromatography [18].

References