LISTSERV 16.0 - PARKINSN Archives

Thanks for this insight Joao Paulo, to think otherwise would
be a total bummer!

I attended an educational meeting last year and the speaker
was Dr. A. Rajput... His topic included toxicity and levodopa
and he said that examination of the brains of people who had
passed away (from natural causes) after long histories of levadopa
therapy showed no evidence of levadopa toxicity. See refer. below...

PMID: 9380042
1: Mov Disord 1997 Sep;12(5):634-8

Is levodopa toxic to human substantia nigra?

Rajput AH, Fenton Me, Birdi S, Macaulay R
Division of Neurology, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
Levodopa (LD) is the most effective drug for symptomatic control of Parkinson's disease, but has
been suspected to be toxic to substantia nigra (SN) dopaminergic neurons. Tissue culture and
animal studies of LD toxicity have produced contradictory evidence, and one study reported that
a human subject exposed to a large cumulative dose (cd) of LD over 4 years had no evidence of
SN damage. We report the cases of five patients, each of whom received a large cd of LD over a
long period. Fluorodopa positron-emission tomography performed in one case indicated
parkinsonism. Autopsies in two cases indicated a normal SN in one and a hypopigmented SN
with normal cell complement in the other. Three patients had essential tremor, one had
nonprogressive parkinsonism, and one had dopa-responsive dystonia. LD (without
decarboxylase inhibitor) was administered over 21 years (cd = 21.99 kg), 9 years (cd = 6.6 kg),
26 years (cd = 18.7 kg), 11 years (cd = 3 kg), and 26 years (cd = 23.93 kg), respectively. None
of the patients with essential tremor developed clinical features of parkinsonism that indicated
significant SN damage, and one had a normal SN at autopsy. The parkinsonian patient
displayed no detectable acceleration of disease process, and the patient with dopa-responsive
dystonia had a normal complement of SN neurons at autopsy. We conclude that LD,
administered at a dose commonly used for treating Parkinson's disease, was not toxic to SN
neurons in these cases.
Comment in: Mov Disord 1998 Mar;13(2):369-70
PMID: 9380042, UI: 98017537

Is Levodopa Toxic or Not?
http://www.wbsaunders.com/nnc/abs/abs2_5/v2n5p244.html

PMID: 9585350
Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their
recovery, in rats with moderate nigrostriatal lesions.

PMID: 10554050
Levodopa in Parkinson's disease: neurotoxicity issue laid to rest?

PMID: 9633686
Levodopa neurotoxicity: experimental studies versus clinical relevance.

PMID: 10495031
The initial treatment of Parkinson's disease should begin with levodopa.

On 18 Jun 2000, at 21:57, Joao Carvalho wrote:

About a recent question on the subject by a list member :
--------
LONDON, ENGLAND -- May 28, 1999 --

Levodopa Slows The Progression Of Parkinson's Disease

The toxicity of levodopa (L-dopa) has long been debated.
This is an important issue because L-dopa is the mainstay of
therapy for Parkinson's disease and treatment can sometimes be
delayed because of fear of the drug's toxicity.

In this week's issue of The Lancet, Katrina Gwinn-Hardy and
colleagues report the findings of a study into the effects of L-dopa
on Parkinson's disease in a family with a history of the disease.

Family members living after 1969 received L-dopa and those who
died before 1969 did not. The researchers found that those treated
with L-dopa had longer survival and slower progression of the
disease compared with those who were untreated.

"Although clinical data cannot directly address the issue of
neurotoxicity, they suggest that therapy should be started without
delay or fears concerning toxicity", researchers write.