Novel dopamine releasing response of an anti-convulsant agent with possible anti-Parkinson's activity.
We used cerebral microdialysis to assess the ability of the anticonvulsant drug Zonisamide (ZNS) to release striatal dopamine in 6-hydroxydopamine nigrotomized rats. Following exogeneously administered ZNS we measured dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in striatal dialysates obtained from the ipsilateral side of the nigrotomy. ZNS administration alone had no effect on levels of DA and its metabolites or rotational behavior. Administration of carbidopa-levodopa alone led to small but insignificant increases in rotational behavior contralateral to the side of the nigrotomy but no corresponding increases in indices of striatal catecholamine release. In contrast, if animals were preloaded with carbidopa and ZNS was co-administered with levodopa 30 minutes later significant increases in contralateral rotational behavior occurred within 20 minutes of ZNS-levodopa injection that lasted for at least 90 minutes. In contrast to the uniform rotational behavioral responses observed in all our nigrotomized animals, less than half demonstrated neurochemical evidence of DA release. In these "responder" animals DOPAC levels increased 300% following carbidopa-levodopa-ZNS administration. We conclude that these results support previously reported findings and provide additional evidence that the anticonvulsant ZNS appears to possess anti-Parkinson's properties. ZNS could therefore be a novel agent for the treatment of PD that could delay the use of or reduce the amount of levodopa needed to treat patients with PD.
Gluck
M R
MR
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. Martin.Gluck@med.va.gov
Santana
L A
LA
Granson
H
H
Yahr
M D
MD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D017551:Microdialysis; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D000078305:Zonisamide
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007555:Isoxazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D000078305:Zonisamide; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D004298:Dopamine; D006719:Homovanillic Acid