Hello list:
Here are two Abstracts from different investigators.
There is an ongoing debate about the toxicity of
chronic use of Levodopa.
Diskinesia comes with the use of L-Dopa, but,
increased cell death is still debated.
What happens in monkeys,
is usually indicative of what happens in humans.
Ray
..............................................................................
Ann Neurol 2001 Aug;50(2):254-7
Levodopa induces dyskinesias in normal squirrel monkeys.
Togasaki DM, Tan L, Protell P, Di Monte DA, Quik M, Langston JW.
The Parkinson's Institute, Sunnyvale, CA 94089, USA.
[log in to unmask]
This study assessed whether or not levodopa induces dyskinesias in normal (ie,
unlesioned) squirrel monkeys. All six animals treated twice daily with levodopa
(15 mg/kg with carbidopa by oral gavage) for two weeks developed choreoathetoid
dyskinesias, whereas none of the vehicle-treated animals displayed any abnormal
movements. These dyskinesias did not merely reflect a generalized motor
activation as locomotion was actually suppressed. The present data demonstrate
that preexisting nigrostriatal damage is not necessary for the development of
levodopa-induced dyskinesias.
PMID: 11506410 [PubMed - in process]
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Psychopharmacology (Berl) 2001 Aug;156(4):402-9
L-Dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic
observations.
Pearce RK, Heikkila M, Linden IB, Jenner P.
Neurodegenerative Diseases Research Centre, Hodgkin Building, Division of
Pharmacology and Therapeutics, GKT School of Biomedical Sciences, King's College
London, Guy's Campus, London Bridge, London SE1 1UL, UK. [log in to unmask]
RATIONALE: L-Dopa induces dyskinesias during the treatment of Parkinson's
disease and also in primates with nigrostriatal lesions produced by MPTP,
but it
is claimed that L-dopa does not provoke dyskinesia in humans or monkeys
with an
intact or mildly damaged nigrostriatal system. OBJECTIVES: This study assessed
the behavioural and pharmacokinetic effects of chronic oral administration of
L-dopa plus carbidopa alone, or with co-administration of the peripheral COMT
inhibitor entacapone, to normal macaque monkeys. Repeated high dose L-dopa
administration was shown to induce marked dyskinesias in monkeys with an intact
nigrostriatal system, and the threshold for dyskinesia expression was increased
by peripheral catechol-O-methyltransferase inhibition with entacapone. METHODS:
Six groups of normal macaque monkeys (n=8 per group; Macaca fascicularis) were
treated with L-dopa (20, 40 or 80 mg/kg) plus carbidopa (5, 10 or 20 mg/kg) with
or without the catechol-O-methyltransferase inhibitor entacapone (20, 40 or 80
mg/kg), or with entacapone alone (80 mg/kg), by oral administration once daily
for 13 weeks. RESULTS: Eleven of 16 animals receiving high dose L-dopa (80 mg/kg
plus carbidopa 20 mg/kg PO with or without entacapone 80 mg/kg PO for 13 weeks)
gradually developed reproducible and idiosyncratic combinations of chorea,
athetosis and dystonia maximal at 60-100 min after L-dopa administration, which
progressively intensified over the course of the study. The dyskinesias observed
were similar in type and distribution to L-dopa-induced dyskinesia observed in
patients with Parkinson's disease and in MPTP-treated primates. The occurrence
of dyskinesia correlated with plasma concentrations of L-dopa, with animals
displaying the most severe dyskinesias having significantly higher plasma
concentrations of L-dopa one hour after dosing than animals with mild or
moderate dyskinesia or no dyskinesia. Co-administration of entacapone with
L-dopa plus carbidopa significantly lowered peak plasma concentrations of L-dopa
and this was reflected by a decrease in the severity of dyskinesias, with only
one animal receiving entacapone and high dose L-dopa plus carbidopa showing
severe dyskinesia, while four receiving high dose L-dopa plus carbidopa alone
did so. CONCLUSIONS: These results show for the first time that chronic oral
L-dopa administration can provoke dyskinesias in primates independently of
nigrostriatal damage, and that this effect is dose related.
PMID: 11498717 [PubMed - in process]
.............................................................................
Ray Strand
Prairie Sky Design
-----------------( on the Edge of the Prairie Abyss )---------------
when the sky is clear
the ground is visible
49/dx PD 2 yrs/40? onset
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