From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Fri Feb 07 2003 - 10:37:13 MST
ct quoted a news release about possible cardiovascular side-effects of
levodopa
### Yes, I heard about it. What does it have to do with selegiline?
Since dopa-sparing with selegiline does not prolong survival in PD (as shown
by DATATOP), any findings about levodopa's side effects are irrelevant here
because we already know selegiline wouldn't make any difference.
Rafal
:
> At 02:28 PM 2/6/2003 -0500, you wrote:
>
> gts wrote:
>> As stated in the following abstract, from DATATOP, "The study found
>> that deprenyl [selegiline] treatment almost halved the risk of
>> reaching a stage of Parkinsonism at which the start of levodopa
>> treatment becomes imperative for lessening disability."
>> That looks like potent neuroprotection to me.
>
> ### It isn't. DATATOP found a *delay* in reaching the
> levodopa-requiring level of symptomatology, not a reduction in total
> risk. At the same time, there was no delay in time to dyskinesias on
> levodopa, and no delay of death. In other words, patients treated
> with selegiline had the same or higher level of disability as
> patients on levodopa, levodopa became equally ineffective at the same
> time, and they died at the same rate. The delay to levodopa is
> strictly due to the symptomatic effect of selegiline
>
> As background: there was once a hypothesis that levodopa accelerates
> the attrition of dopaminergic neurons, and that levodopa-sparing
> therapy would delay the onset of dyskinesias which usually develop
> after about 5-7 years on levodopa, and perhaps prolong survival. A
> nice hypothesis, but not true - substituting dopa-agonists or
> selegiline for levodopa in initial treatment does not delay the onset
> of dyskinesia. ... Rafal
> ==========================================================
> February 6, 2003
> Parkinson's disease: gold standard drug causes heart problems
>
> Research has shown that levodopa can increase the risk of heart
> disease in Parkinson's patients.
> January 30, 2003 3:58 PM GMT (Datamonitor) - A study published in the
> Archives of Neurology suggests a link between levodopa and increased
> homocysteine levels. This new evidence of adverse side effects will
> increase the demand for treatments that can delay the need for
> levodopa. Competition will be strong in the $2 billion market and
> Pharmacia and GSK are leading the way with their dopamine agonists
> Mirapex and Requip respectively.
>
> People with Parkinson's disease (PD) who take the drug levodopa
> appear to have a higher than average risk of heart disease, according
> to researchers at the University of Texas Southwestern Medical Center
> in Dallas. However, researchers stress it is not clear whether
> levodopa itself raises heart disease risks. Experts believe these
> preliminary findings "raise certain concerns" about the safety of
> levodopa, but are not meant to discourage people from taking the drug.
> PD affects over 560,000 people in the US. It is a progressive,
> degenerative condition of the central nervous system, characterized
> by symptoms such as tremor, rigidity, slowness of movement and
> postural instability. Levodopa works by replacing levels of the
> neurotransmitter dopamine in the brain, although continued use is
> associated with undesirable movement side effects known as
> dyskinesias. Moreover, the treatment cannot slow disease progression
> and works only to alleviate the symptoms. After experiencing a
> relatively static five years, the PD market is set to grow with the
> recent emphasis on the dopamine agonist class of drugs, which are now
> recommended as first-line monotherapy. The leading players,
> GlaxoSmithKline and Pharmacia, will drive this growth with ReQuip
> (ropinirole) and Mirapex (pramipexole) respectively. The market is
> also set to expand with the emergence of revolutionary combination
> drug strategies that aim to reduce levodopa induced motor
> fluctuations and dyskinesias, as well as neuroprotective therapies
> that delay disease progression. Levodopa remains the gold standard
> treatment of PD, despite being over 30 years old and the emergence of
> new drug classes. It is now highly generacized, although controlled
> release versions of Roche's Madopar and BMS-DuPont's Sinemet are
> popular levodopa therapies in Europe and US respectively. Even so,
> the high volume of sales means the market for levodopa therapies is
> worth over a billion dollars. This new evidence to suggest a
> heightened risk of heart disease will increase the need for therapies
> that can further delay levodopa treatment.
> ==========================================================
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