[Therapy of Parkinson's disease--up to date].
The prognosis of Parkinson's disease (PD) has been improved with developing anti-parkinsonian agents. Recently the re-evaluation of L-dopa and dopamine agonists is the topic in the world based on focusing non motor side effects of dopamine agonists such as sudden uncontrollable somnolence and valvulopathy in place of motor complication. The development of anti-parkinsonian drugs based on the new mechanism has been progressed such as CEP-1347, AAV-neuturin, AAV-GAD, and AAV-DDC. The most reliable new drug is zonisamide which is originally synthesized in Japan for epilepsy. A nation-wide randomized double blind study showed that Zonisamide improves motor function of advanced PD patients. Long-term efficacy was also shown. The mechanism of zonisamide for PD is the increase of dopamine synthesis and moderate inhibition of monoamine oxydase B activity. Inhibitatory effects of sodium channel and T-type calcium channel may also affects. Zonisamide has neuroprotective effects though inhibition of quinoprotein and increasing the levels of GSH and Mn SOD. Up to now we have no agents with clinically evidenced neuroprotective effects for PD. Base on the results of ELLDOPA study and "delayed start" clinical trials the most important concept for neuroprotection may be the early dopaminergic support for the degenerating dopaminergic system.
Murata
Miho
M
Department of Neurology, National Center Hospital of Neurology & Psychiatry.
D000927:Anticonvulsants / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002227:Carbazoles; D015259:Dopamine Agents / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D015195:Drug Design; D015316:Genetic Therapy; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use; D018696:Neuroprotective Agents; D010300:Parkinson Disease / Q000209:etiology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D013378:Substantia Nigra / Q000637:transplantation; D000078305:Zonisamide
D000927:Anticonvulsants; D000978:Antiparkinson Agents; D002227:Carbazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; D007555:Isoxazoles; D018696:Neuroprotective Agents; C106592:3,9-bis((ethylthio)methyl)-K-252a; D000078305:Zonisamide; D007980:Levodopa