Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro.
Pretreatment with bromocriptine (5 mg/kg, i.p., 7 days) completely protected against the decrease in mouse striatal dopamine and its metabolites induced by intraventricular injection of 6-hydroxydopamine after intraperitoneal administration of desipramine, but similar pretreatment with L-DOPA/carbidopa (75/7.5 mg/kg, i.p., 7 days) showed only partial protective effect. Furthermore, in an in vitro system that generated.OH from FeSO4-H2O2, bromocriptine dose-dependently reduced the number of .OH radicals. These findings indicate that bromocriptine has a neuroprotective effect against neurotoxins such as 6-hydroxydopamine, probably due, in part, to its hydroxyl radical scavenging activity and inhibiting effect on dopamine turnover rate. This suggests that early introduction of bromocriptine in the therapy of Parkinson's disease may be superior to treatment with L-DOPA alone.
Ogawa
N
N
Department of Neuroscience, Okayama University Medical School, Japan.
Tanaka
K
K
Asanuma
M
M
Kawai
M
M
Masumizu
T
T
Kohno
M
M
Mori
A
A
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical; D007276:Injections, Intraventricular; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016627:Oxidopamine / Q000037:antagonists & inhibitors*
D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D001971:Bromocriptine; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D003891:Desipramine; D004298:Dopamine