VELNACRINE IN ALZHEIMERS-DISEASE - AN INITIAL APPRAISAL OF ITS CLINICAL POTENTIAL

Velnacrine is an hydroxylated derivative of the acetylcholinesterase i nhibitor tacrine. The ability of velnacrine to increase cholinergic ne urotransmission in vitro provides the rationale for its investigation as a potential treatment in patients with Alzheimer's disease, who are known to have reduced acetylcholine levels in the central nervous sys tem. Single doses of velnacrine (100 or 150mg) attenuated cognitive im pairment induced by central cholinergic blockade in healthy volunteers , and memory improved significantly in a small number of patients with Alzheimer's disease administered a 75mg dose. Evidence of efficacy fo r velnacrine is limited to results of briefly reported placebo-control led studies. When administered in dosages of up to 225 mg/day for 6 we eks, velnacrine appeared to confer modest benefit in about one-third o f 423 patients with Alzheimer's disease enrolled in a US dose-finding trial. Velnacrine 150 mg/day for 10 days was also considered superior to placebo in a small European trial involving 35 patients, notably in its effects on language, praxis and memory. Fuller results are antici pated from a 6-month investigation demonstrating efficacy for velnacri ne 150 or 225 mg/day at 12-week interim analysis. Of interest is the f inding from this trial that caregiver time assessed at 24 weeks was sh orter for velnacrine compared with placebo recipients.