Hello, Dietmar:
You ask about:
> a new drug is supposed to be released on the market next spring or summer.
>The research name is "COMT", some sort of blocker, more effective than
>pergolide (agonist).
>....is not yet sure where this drug will be available first (USA or Sweden)
>and what will be the trademark. Does anybody know about this drug?
I am enclosing two sources of information about Entacapone and Tolcapone --
we are eagerly awaiting their availability on both sides of the Atlantic.
Source
Gen Pharmacol, 25: 5, 1994 Sep, 813-24
Abstract
1. The structure of catechol O-methyltransferase (COMT) has been
recently characterized and a series of new and selective COMT
inhibitors developed. 2. Entacapone, nitecapone and tolcapone are
nitrocatechol-type potent COMT inhibitors in vitro (Ki in nanomolar
range). They are also very selective for COMT and active in vivo even
after oral administration. CGP 28014 is a pyridine derivative that is
active only in vivo. 3. In animal studies, these compounds inhibit
effectively the O-methyla tion of L-dopa, thus improving its
bioavailability and brain penetration and potentiating its behavioural
effects.
4. Entacapone and nitecapone have mainly a peripheral
effect whereas tolcapone and CGP 28014 also inhibit O-methylation in
the brain. 5. In man, entacapone, nitecapone and tolcapone all inhibit
dose dependently the COMT activity in erythrocytes. These COMT
inhibitors also decrease the amount of COMT dependent metabolites of
adrenaline and noradrenaline in plasma. 6. In human volunteers,
entacapone, tolcapone and CGP 28014 improve the bioavailability of
L-dopa and inhibit the formation of 3-O -methyldopa. 7. In the first
clinical studies in patients with Parkinson's disease, both entacapone
and tolcapone potentiate and prolong the therapeutic effect of L-dopa.
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VIENNA, Austria, June 18 /PRNewswire/ -- According to results
announced at this week's 4th International Congress of Movement
Disorders, a new Parkinson's medication called entacapone
reduces fluctuations in motor performance that commonly occur in
patients being treated with levodopa.
The SEESAW (Safety and Efficacy of Entacapone Study Assessing
Wearing Off) study found that entacapone managed these
fluctuations, while prolonging the effectiveness of levodopa and
reducing the need for levodopa increases. The trial was
conducted by the Parkinson's Study Group (PSG), a leading
consortium of Parkinson's disease (PD) researchers.
Entacapone belongs to a new class of drugs under investigation
known as catechol-O-methyltransferase or COMT-inhibitors, which
have a novel mechanism of action. These agents have been shown
to be safe and effective with other adjunctive PD medications and
to prolong the duration of action of levodopa, thus avoiding
problems related to levodopa's "wearing off" phenomenon.
Traditionally the mainstay of PD treatment, chronic levodopa use
leads to motor fluctuations and involuntary movements.
"Of particular importance, these patients were able to
continue all other anti-Parkinsonian medications including
dopamine agonists and selegiline," said Karl Kieburtz, MD, MPH,
Associate Professor of Neurology, University of Rochester, New
York, USA. "The introduction of entacapone therefore provided a
significant additional benefit even in the presence of
conventional therapies."
The study included 205 optimally-treated patients with
levodopa- related motor fluctuations at 18 centers in the US and
Canada. The participants were randomized to receive either
entacapone (200 mg daily) or placebo with each dose of
carbidopa/levodopa and were followed for 28 weeks.
At 24 weeks, Unified Parkinson's Disease Rating Scale (UPDRS)
scores had worsened by three points in the placebo group, who
were taking 20.7 mg more levodopa. UPDRS scores improved by one
point in the entacapone treatment group, who required 101.9 mg
less levodopa. Entacapone also increased "on" or good time
significantly (p 0.005). UPDRS is a standard international tool
to measure functional ability.
"This is significant as Parkinson's disease is a chronic
disorder and patients progressively decline over time," added Dr.
Kieburtz. "A significant improvement in motor scores, as shown
in the SEESAW trial, is therefore very positive."
Several other presentations at the meeting provided evidence
of entacapone's therapeutic potential. Among them, Scandinavian
researchers from 16 clinical sites, led by Urpo K. Rinne, MD,
PhD, Professor of Neurology, University of Turku, Finland, found
that "on" time based on home diaries increased significantly in
entacapone- compared with placebo-treated patients. The results
persisted throughout the six-month study. The trial included 171
patients who had developed motor fluctuations during optimal
levodopa treatment.
Entacapone was generally well tolerated, although there was a
slight increase in gastrointestinal side effects including nausea
and abdominal pain.
Parkinson's disease is a chronic, progressive neurological
disorder that affects motor function. Primary symptoms include
muscle rigidity, tremor, a decrease in the range and frequency of
voluntary movements, and abnormalities in posture and gait.
The studies were sponsored by Orion Pharma of Finland.
Entacapone will be co-marketed internationally by Sandoz Pharma
Ltd.
Regards,
Margaret Tuchman (54 yrs, dx 1980)
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
I've got Parkinson's disease. And he's got mine.
