Velnacrine for the treatment of Alzheimer's disease: A double-blind, placebo-controlled trial

F. P. Zemlan, D. G. Folks, B. J. Goldstein, G. Gottlieb, R. F. Holub, R. D. Linden, R. A. Margolin, R. W. Richter, W. F. Speakman, R. L. Strub

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The present study examines the safety and efficacy of the centrally acting cholinesterase inhibitor, velnacrine, in treating the cognitive symptoms of Alzheimer's disease. Seven hundred thirty-five patients with mild-to-severe Alzheimer's disease were treated in a double-blind, placebo-controlled study. Following the screen visit, patients were treated with velnacrine (10, 25, 50 and 75 mg t.i.d.) or placebo in a double-blind dose-ranging study to identify velnacrine-responsive patients and their best dose. Following placebo washout velnacrine responsive patients were randomly assigned to their best dose of velnacrine (N = 153) or placebo (N = 156) in a six week double-blind dose-replication study. Primary efficacy measures were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS) and the Physician's Clinical Global Impression of Change. Statistically significant improvement was observed in both primary efficacy measures in velnacrine-treated patients during the dose-replication study. Velnacrine patients scored better on the cognitive subscale of the ADAS than placebo patients (P < 0.001), with patients receiving the highest velnacrine dose averaging a 4.1-point improvement with respect to screen values. Clinical Global Impression of Change scores of velnacrine-treated patients were significantly improved at the end of the 6 weeks of treatment when compared to those of placebo patients (P < 0.05). The most common side effect was asymptomatic elevation in liver transaminase levels, which occurred among 29% of patients. These data suggest that velnacrine produces modest clinical improvement in a subset of patients with mild-to-severe Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1105-1116
Number of pages12
JournalJournal of Neural Transmission
Issue number8-9
StatePublished - Nov 26 1996


  • Alzheimer's disease
  • Cholinesterase inhibitor
  • Psychparmacology
  • Velnacrine

ASJC Scopus subject areas

  • Neuroscience(all)


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