Zonisamide: chemistry, mechanism of action, and pharmacokinetics

@article{Leppik2004ZonisamideCM,
  title={Zonisamide: chemistry, mechanism of action, and pharmacokinetics},
  author={Ilo Leppik},
  journal={Seizure},
  year={2004},
  volume={13},
  pages={S5-S9}
}
  • I. Leppik
  • Published 2004
  • Chemistry, Medicine
  • Seizure
Zonisamide is a synthetic 1,2-benzisoxazole-3-methanesulfonamide with anticonvulsant properties. The sulfamoyl group on zonisamide was expected to suppress seizures in a manner similar to another sulfonamide analogue, acetazolamide, through inhibition of carbonic anhydrase. However, this does not appear to be the primary mechanism of action since zonisamide requires much higher doses than acetazolamide to achieve equivalent titration in vivo. Studies with cultured neurons indicate that… Expand
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Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative
TLDR
The metabolism of zonisamide in vitro was characterized through aerobic and anaerobic incubations with rat liver subcellular fractions and cultured gastrointestinal microflora and produced a single metabolite, 2-(sulphamoylacetyl)-phenol (2-SMAP), by reductive cleavage of the 1,2-benzisoxazole ring. Expand
Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative.
TLDR
Metabolism of zonisamide in vitro by hepatic subcellular fractions and cultured gastrointestinal flora produced a single metabolite, 2-(sulphamoylacetyl)-phenol (2-SMAP), by reductive cleavage of the 1,2-benzisoxazole ring. Expand
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Findings suggest that the dosage of zonisamide in epileptic patients might need to be varied depending on the comedication, and the RBC/plasma ratio varied eightfold within a given curve. Expand
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TLDR
In rats, rabbits and dogs, the anticonvulsant activity of AD-810 against maximal electroshock seizures was more potent than those of diphenylhydantoin and carbamazepine, providing a high protective index as well as other favorable properties. Expand
Steady‐State Pharmacokinetics of Zonisamide, an Antiepileptic Agent for Treatment of Refractory Complex Partial Seizures
TLDR
A 56‐day pharmacokinetic study of zonisamide was conducted in 24 healthy volunteers, and steady state was achieved in 29 days including two dose escalations, and in an average of 15 days from the last dose adjustment, demonstrating that zonisamia is not an autoinducer. Expand
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TLDR
The results imply that zonisamide is metabolized reductively to SMAP by a cytochrome P450 belonging to the 3A subfamily under aerobic conditions as well as anaerobic conditions. Expand
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TLDR
Findings show that when ZNS is administered concomitantly with these anti-epileptic drugs, it is necessary to monitor the plasma concentration of ZNS in order to adjust its dosage. Expand
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TLDR
The safety and efficacy of zonisamide (ZNS), a new antiepileptic drug, was tested in 167 adult participants who entered a historical-controlled 16-week open label, multicenter study and four persons developed kidney stones and were withdrawn from the study 250-477 days after starting ZNS. Expand
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TLDR
It is demonstrated that ZNS possesses potent anticonvulsant action against focal seizure and its secondary generalization from the visual cortex. Expand
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