The dopamine agonist pramipexole scavenges hydroxyl free radicals induced by striatal application of 6-hydroxydopamine in rats: an in vivo microdialysis study.
Hydroxyl free radical production seems to play an important role in the pathogenesis of Parkinson's disease. In the present study, we investigated the dopamine agonists pramipexole and pergolide as well as the nitrone compound S-PBN (N-tert-butyl-alpha-(2-sulfophenyl)nitrone) to reduce hydroxyl radical formation. Microdialysis experiments were carried out in non-anaesthetized Wistar rats. Salicylate was incorporated into the perfusion fluid to measure indirectly hydroxyl radicals indicated by 2,3-dihydroxybenzoic acid (2,3-DHBA). Local perfusion with 0.2 or 2 nmol/2 microl/min 6-hydroxydopamine (6-OHDA) via the microdialysis probe significantly increased 2,3-DHBA levels 14-fold and 47-fold, respectively. Systemic application of either pergolide (0.05 mg/kg) or pramipexole (1 mg/kg) failed to significantly reduce 6-OHDA-induced hydroxyl radical production. In contrast, a 40 min pretreatment with pramipexole (2 and 10 nmol/2 microl/min via the probe) before onset of 6-OHDA perfusion, significantly attenuated 2, 3-DHBA levels compared with vehicle controls. S-PBN pretreatment (2 nmol/2 microl/min) was not effective to reduce 2,3-DHBA levels. In conclusion, pramipexole was able to reduce hydroxyl radical levels induced by 6-OHDA in vivo after local application. This property of pramipexole may be beneficial under conditions of enhanced hydroxyl radical formation in parkinsonian brains and may add to its well known dopamine D(2)-like receptor agonistic effects.
Ferger
B
B
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland. ferger@toxi.biol.ethz.ch
Teismann
P
P
Mierau
J
J
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D016627:Oxidopamine / Q000494:pharmacology; D010479:Pergolide / Q000494:pharmacology*; D000077487:Pramipexole; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*
D018663:Adrenergic Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D062385:Hydroxybenzoates; D013844:Thiazoles; D010479:Pergolide; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D000077487:Pramipexole; D016627:Oxidopamine; D004298:Dopamine