The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: is continuous dopaminergic stimulation necessary?
Identifieur interne : 002119 ( Ncbi/Curation ); précédent : 002118; suivant : 002120The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: is continuous dopaminergic stimulation necessary?
Auteurs : Christos Tsironis [Grèce] ; Marios Marselos ; Angelos Evangelou ; Spiridon KonitsiotisSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2008.
English descriptors
- KwdEn :
- Animals, Basal Ganglia (pathology), Dopamine Agonists (adverse effects), Dopamine Agonists (therapeutic use), Dose-Response Relationship, Drug, Drug Administration Schedule, Dyskinesia, Drug-Induced (etiology), Levodopa (adverse effects), Levodopa (therapeutic use), Parkinson Disease (drug therapy), Parkinson Disease (pathology), Rats, Rats, Wistar.
- MESH :
- chemical , adverse effects : Dopamine Agonists, Levodopa.
- drug therapy : Parkinson Disease.
- etiology : Dyskinesia, Drug-Induced.
- pathology : Basal Ganglia, Parkinson Disease.
- chemical , therapeutic use : Dopamine Agonists, Levodopa.
- Animals, Dose-Response Relationship, Drug, Drug Administration Schedule, Rats, Rats, Wistar.
Abstract
The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments. Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 +/- 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 +/- 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 +/- 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 +/- 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was "low dopaminergic stimulation" with one low daily dose, instead of trying to achieve "continuous dopaminergic stimulation" using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa.
DOI: 10.1002/mds.21630
PubMed: 18442128
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Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 +/- 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 +/- 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 +/- 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 +/- 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was "low dopaminergic stimulation" with one low daily dose, instead of trying to achieve "continuous dopaminergic stimulation" using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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