Zonisamide: a new drug for Parkinson's disease.
Zonisamide, a benzisoxazole derivative, is an antiepileptic drug with a long half-life. Three nationwide, double-blind, placebo-controlled studies carried out in Japan prompted the approval of zonisamide as an antiparkinsonian agent in early 2009. The addition of zonisamide at 25-50 mg/day to currently used antiparkinsonian drugs significantly improved cardinal symptoms in patients with advanced Parkinson's disease. The effects were maintained over more than 1 year even in patients with advanced disease. Zonisamide has multiple modes of action, and its effects on Parkinson's disease include activation of dopamine synthesis, inhibition of monoamine oxidase, inhibition of T-type calcium channels and inhibition of an indirect pathway in the basal ganglia through the δ opioid receptor. Furthermore, zonisamide exhibits neuroprotective effects in animal models of Parkinson's disease. It strongly inhibits quinoprotein formation and markedly increases glutathione S-transferase levels in the striatum by enhancing the astroglial cysteine transport system and/or astroglial proliferation via S100beta production and secretion.
Murata
Miho
M
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. mihom@ncnp.go.jp
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006207:Half-Life; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D014018:Tissue Distribution; D000078305:Zonisamide
D000927:Anticonvulsants; D000978:Antiparkinson Agents; D007555:Isoxazoles; D018696:Neuroprotective Agents; D000078305:Zonisamide