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Title: DG DISPATCH - ISSSAT: Dual Action of Galantine Boosts Neurotransmission in Patients with Alzheimer's
URL: http://www.pslgroup.com/dg/195BFE.htm
Doctor's Guide
April 10, 2000


By Cameron Johnston
Special to DG New

STOCKHOLM, SWEDEN -- April 10, 2000 -- A drug that is now available in Sweden, and is being considered for release in the rest of the European countries, could represent the next generation of treatment for alleviating some of the symptoms of Alzheimer's disease.

Reminyl (galantamine), according to scientists at Janssen Research in Belgium, where the drug was developed, is unique because it acts on two separate aspects of neurotransmission within the brain. On one hand, it is an acetylcholinesterase inhibitor -- the same as the other drug presently used to treat Alzheimer's symptoms, Aricept.

Put simply, the nerve cells in the brain fire their messages in the form of acetylcholine, but the acetylcholinesterase enzyme breaks down the acetylcholine so the message never reaches the other side of the synaptic gap, or it crosses the gap in a garbled form. Both Reminyl and Aricept (donepezil) block this enzyme from being produced so more of the acetylcholine is able to successfully cross the synaptic gap.

But the other mechanism of Reminyl is that it acts on nicotinic receptors, which are a form of neurotransmitter receptor on the other side of the gap. In a simple sense, the drug sensitizes these receptors so they will still respond to smaller amounts of the neurotransmitter that reaches them. This second mechanism of action actually highlights -- or augments -- the acetylcholine action of nerve signaling, doctors say.

In clinical trials, Reminyl has been shown to produce improvements on several scales and tests that are used to determine a person's cognitive impairment. Just over 350 patients received the drug (either 16 or 24 mg/day) for a year and were maintained either at or above their baseline scores on the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog). This is the most commonly-used instrument for measuring various forms of memory loss.

Patients receiving Reminyl also scored significantly better than those in the placebo group on the Clinicians Interview-Based Impression of Change plus Caregiver's input scale (CIBIC-Plus), on their Mini Mental State scores, and on the Disease Affecting Disability (DAD) scale.

To date, more than 3,000 patients have been tested worldwide with Reminyl.

Doctors speculate that while the acetylcholinesterase inhibition means the drug mimics Aricept and other drugs that are under development for the treatment of Alzheimer's disease, the fact that the nicotinic receptors are sensitized provides a significant, added boost to the way neurotransmitters are sent through the brain. It has even been suggested that this action alone may be the drug's strongest feature and that its acetylcholinesterase inhibiting activity is a bonus.

Either way, the modulation of these receptors could lead to greater release of acetylcholine, says Dr. Luc Truyen, Janssen's associate director of clinical global research. Therefore, it may "represent an important milestone in the treatment of 'Alzheimer's disease."

The results of four studies with Reminyl were presented at the 6th International Stockholm-Springfield Symposium on Alzheimer Therapy (ISSSAT) which ended Sunday (April 9) in Stockholm.

Related Links: Reminyl (galantamine) and Aricept (donepezil).

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