Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.
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PMID:Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. 832 80

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.
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PMID:[Research and development of zonisamide, a new type of antiepileptic drug]. 883 Dec 58

Progressive myoclonic epilepsy (PME) syndromes are intractable to most antiepileptic drugs (AED). The course of these diseases, results in almost total dependency due to continuous myoclonias, repeated episodes of status epilepticus, ataxia and dementia. The need for new treatment strategies is therefore imperative. Zonisamide has previously been reported to be effective in two patients with PME. Case reports of seven patients (ages 19-42) with Unverricht-Lundborgs disease (ULD) and one Lafora Body Disease are presented. Zonisamide was given at doses of 100-600 mg/day for a period of 2 to 3 years. Concomitant AEDs were usually valproate and a benzodiazepine. Zonisamide dramatically reduced the amount of myoclonias and generalized seizures. In three of the cases, the initial dramatic effect on myoclonias wore off after 2-4 years of treatment but patients still experienced moderate efficacy for generalized tonic-clonic seizures. The dramatic reduction of stimulus sensitivity for light, touch and startle by zonisamide was sustained in all patients with ULD. Zonisamide may be a useful agent in the treatment of PME. Controlled clinical trials are warranted to further investigate the antiepileptic effects of this drug, in difficult to treat epileptic syndromes.
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PMID:Zonisamide for progressive myoclonus epilepsy: long-term observations in seven patients. 947 42