I thought I would forward this message from the sci.med Usenet newsgroup
on for those who may not have access.
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Date: Thu, 09 Jun 94 05:09:46 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: New Drug Treatments for Parkinson's Disease
New Drug Treatments on Parkinson's Disease
APDA Newsletter, Winter 1993-1994
Abraham Lieberman, M.D.
Chief Movement Disorders
Barrow Neurological Institute
Phoenix, AZ
Chairman, APDA Medical Advisory Board
Levodopa combined with carbidopa (Sinemet, Atamet) remains the mainstay of
Parkinson's disease (PD) treatment. Initially, most patients respond well.
Indeed, failure to respond to levodopa indicates a condition other than PD.
After an initial good response, most patients develop daily response
fluctuations, the "on- off" effect, after 2 to 5 years of treatment. These
fluctuations are related in part to progression of PD and in part to
levodopa metabolism. Several drugs are used to reduce fluctuations. These
include a long acting levodopa preparation (Sinemet CR) and drugs that
block one of the enzymes that break down dopamine, like deprenyl
(Eldepryl), and dopamine agonists like (bromocriptine (Parlodel) and
pergolide (Permax)) that supplement the actions of levodopa. While these
treatments are helpful, response fluctuation remains a major problem.
Several new treatments are being developed and tested at selected research
centers. The following treatments are being tested at the Barrow
Neurological Institute in Phoenix, Arizona:
Dopamine Agonists: Three new dopamine agonists which may have
advantages over bromocriptine and pergolide. Cabergoline, like
bromocriptine and pergolide, is an ergot compound. It is longer
acting than bromocriptine and pergolide and is administered on a once
a day basis. Cabergoline is especially useful in patients with
response fluctuations. Ropinerole, a non-ergot agonist with
properties different from Cabergoline, is also useful in patients with
response fluctuations. Pramipexole is an agonist with properties
different from Cabergoline and Ropinerole. In one study Pramipexole
is given to patients with advanced PD who have the "on-off" effect,
while in another study it is administered to patients with early PD.
Pramipexole delays the need for levodopa and is especially useful in
relieving tremor.
Because of differences in the way PD patients respond to drugs it is
important that several agonists be available. MAO Blockers:
Lazebemide, like deprenyl, blocks the enzyme monoamine oxidase (MAO).
And, like deprenyl, it prolongs the actions of levodopa and delays the
need for levodopa. As with the dopamine agonists it is desirable to
have several MAO inhibitors available. In addition to their ability
to increase the effectiveness of levodopa, MAO inhibitors may protect
cells from dying. Trials of all of the MAO inhibitors are now being
conducted in other diseases where neurons (nerve cells) die
prematurely, such as Alzheimer's disease and Amyotrophic Lateral
Sclerosis (ALS/Lou Gehrig's disease).
COMT Blockers: Tolcapone blocks the enzyme COMT, prolonging the
action of levodopa, and markedly reducing the "on-off" effect.
Tolcapone is being studied in patients with advanced PD and will be
studied in patients with early and moderate PD.
Low Protein Diet: A balanced 7:1 carbohydrate/protein ratio food
supplement (Hearty Balance) allows levodopa to act longer. Ninety
seven PD patients with fluctuations were evaluated at 4 separate
centers. The high carbohydrate and 7:1 carbohydrate protein
beverage resulted in significant improvement, in all symptoms measured,
over a high protein beverage. The availability of this palatable, easy
to use, balanced carbohydrate/low protein diet provides a dietary means
of controling response fluctuations.
Growth Factors: CNTF is a trophic growth factor, that is being studied
in ALS. CNTF stimulate the growth of dying cells in the spinal cord and
hopefully will alow them to regenerate. CNTF is one of a class of
compounds that holds promise for the treatment of degenerative diseases
such as PD, ALS, and Alzheimer's disease.
Prior to the advent of trophic factors, treatment of these disorders was
directed at lessening symptoms or possibly, as with MAO inhibitors, at
slowing the progression of PD. Although CNTF is now being used on an
experimental basis only for the treatment of ALS, we hope eventually to
be able to use it in the other diseases. GDNF and BDNF are trophic
factors that are specific for the dopamine producing cells that are
involved in PD.
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