| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
I found the beneficial effects of zoriisamide on Parkinson's disease (Neurosci Res. 2001:41:397-399). Zonisamide improves all the cardinal symptoms of Parkinson's disease such as rigidity, tremor and akinesia especially on wearing-off phenomenon. We have demonstrated that zonisamide 1) increases dopamine synthesis through increasing activity and content8 of tyrosine hydroxylase(TH), 2) increases TH mRNA prior to the increase of TH protein, 3) moderately inhibit monoamine oxydase B (MAOB) activity (IC50=28 μM), 3) has no affinity to dopamine transporter or D1-D5 dopamine receptors, 4) has no direct effects on glutamate receptors (NMDA, AMPA, kinate), serotonine receptors (5HT1-7), or adenosine receptors (A1, A2A, A2B), which seemed to be action points of antiparkinson's drugs other than dopamine system. Zonisamide is a T-type Ca channel blocker. It was reported that this type of blocker increased burst firing of nigral dopamine neuron. We have demonstrated using SH-SY5Y cells /100 μM of NiCl2 (T-type Ca channel blocker) and 300 nM of apamin (SK channel blocker; SK channel is linked to T-type Ca channel on nigral dopamine neuron) increase TH mRNA same time course as zonisamide. This result strongly supports zonisamide increase dopamine synthesis though T-type Ca channel.
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