3-Sulfamoylmethyl-l,2-benzisoxazole, a new type of anticonvulsant drug: Electroencephalographic profile

Ito, Tsugutaka; Hori, Misako; Masuda, Y.; Yoshida, Kouichi; Shimizu, Masanao

doi:10.1016/s0021-5198(19)66865-4

Cited by 6 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zonisamide suppresses both interictal cortical spikes and cortical seizure propagation. 7 It exerts a depressant effect on kainic acid-induced and kindled limbic seizures. 8,9 Zonisamide also blocks seizures induced by maximal electroshock and has variable effects on pentylenetetrazole-induced seizures.…”

mentioning

confidence: 99%

Clinical Experience With Zonisamide Monotherapy and Adjunctive Therapy in Children With Epilepsy at a Tertiary Care Referral Center

2005

View full text Add to dashboard Cite

We evaluated our clinical experience with zonisamide, a broad-spectrum antiepileptic drug, in a group of children with predominantly medically refractory epilepsy. A retrospective chart review was conducted on patients at our tertiary referral center following Institutional Review Board approval. Observers documented reports of seizure frequency, and seizure types were identified either clinically or by prior video-electroencephalography monitoring. We identified 68 patients (age range 1.9-18.1 years [median 6.9 years]; male to female ratio 1.3:1) treated with zonisamide for 0.7 to 28.9 months; at the last visit, 22% and 78% were on monotherapy and adjunctive therapy, respectively. The median duration of treatment and maintenance dose at the end of the follow-up were 11.2 months and 8.0 mg/kg/day, respectively. Seizure types included generalized (primary generalized tonic-clonic, myoclonic, tonic, atonic, absence) and partial (simple, complex, and secondarily generalized tonic-clonic seizures); 10 (15%) patients had both partial and generalized seizures. Sixteen (25.8%) patients were seizure free, although five of them were already in remission prior to starting zonisamide. Thirteen (21.0%) patients had a > 50% seizure reduction, 10 (16.1%) patients had a < 50% seizure reduction, 14 (22.6%) had no improvement in baseline seizures, and 9 (14.5%) reported having increased seizures. The latter were mostly associated with dosage alterations in concomitant antiepileptic drugs. Common side effects were central nervous system related, including behavioral or psychiatric (23.5%), cognitive dysfunction (12.0%), and sedation (10.3%). Eleven (16.2%) patients ultimately discontinued zonisamide, but only five were strictly due to side effects. Zonisamide is clinically effective against multiple seizure types in a significant proportion of children with epilepsy across a broad age range. Drug discontinuation as a result of side effects is uncommon.

show abstract

mentioning

confidence: 99%

Clinical Experience With Zonisamide Monotherapy and Adjunctive Therapy in Children With Epilepsy at a Tertiary Care Referral Center

2005

View full text Add to dashboard Cite

show abstract

Section: Topiramate and Zonisamide: Antiepileptics With Potent Antiobesity Actionmentioning

confidence: 99%

“…(1,2-benzisoxazole-3 methanesulfonamide), is a widely used antiepileptic drug [46,54,55]. In vitro studies with cultured neurons showed that zonisamide blocks repetitive firing of voltage-sensitive sodium channels and reduces voltagesensitive T-type calcium currents without affecting Ltype calcium currents [46,54,55]. Such a complicated mechanism of action may explain its efficacy in patients resistant to other antiepileptic drugs, whereas its pharmacokinetic profile is favorable for clinical use since the drug is rapidly and completely absorbed and has a long half-life (63-69h), which allows twice-or once-daily dosing [46,54,55].…”

Section: Topiramate and Zonisamide: Antiepileptics With Potent Antiobesity Actionmentioning

confidence: 99%

“…In vitro studies with cultured neurons showed that zonisamide blocks repetitive firing of voltage-sensitive sodium channels and reduces voltagesensitive T-type calcium currents without affecting Ltype calcium currents [46,54,55]. Such a complicated mechanism of action may explain its efficacy in patients resistant to other antiepileptic drugs, whereas its pharmacokinetic profile is favorable for clinical use since the drug is rapidly and completely absorbed and has a long half-life (63-69h), which allows twice-or once-daily dosing [46,54,55]. Being an unsubstituted sulfonamide, zonisamide has also been investigated for the inhibition of CA by its discoverers [56,57], being concluded that although it binds significantly to erythrocytes [58] (where two CA isozymes, CA I and II are highly abundant) its CA inhibitory properties are rather weak, and thus, this phenomenon does not play any role in the anticonvulsant activity of the drug [56][57][58].…”

Section: Topiramate and Zonisamide: Antiepileptics With Potent Antiobesity Actionmentioning

confidence: 99%

See 1 more Smart Citation

Polypharmacology of carbonic anhydrase inhibitors

Supuran

Mugelli

2019

Pharm Adv

View full text Add to dashboard Cite

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes all over the phylogenetic tree, with 16 different isoforms present in mammals. CAs are efficient catalysts for the reversible hydration of carbon dioxide to bicarbonate and are inhibited by several classes of compounds such as the sulfonamides and their isosteres, sulfamates and sulfamides. A large number of clinically used drugs/agents in clinical development show significant inhibitory activity against the human (h) CA isoforms. Such compounds have applications as diuretics and antiglaucoma drugs, anticonvulsants, with some derivatives in clinical development as anticancer agents/diagnostic tools, or as antiobesity drugs. Several drugs originally discovered for other targets, such as such as the antiepileptics topiramate, zonisamide, and lacosamide; the sulfonamide coxibs (celecoxib, valdecoxib and paricoxib), or the protein kinase inhibitors pazopanib, imatinib and nilotinib, also show significant inhibition of many pharmacologically relevant CA isoforms. This polypharmacology of the CA inhibitors (CAIs) thus affords for novel applications for these drugs, such as for example the antiobesity action of topiramate and zonisamide (thought to be due to inhibition of two mitochondrial CA isoforms) or the antitumor activity of most sulfonamides and also coxibs and kinase inhibitors, which strongly inhibit the tumor-associated isoforms CA IX and XII. Novel applications of CAIs have also emerged in the treatment of rheumatoid arthritis, neuropathic pain and cerebral ischemia, considering the off-target activity/polypharmacology of well-known, clinically used drugs targeting these enzymes.

show abstract

“…Zonisamide (ZNS) is a relatively new AED developed in Japan, and its beneficial effect on canine epilepsy has recently been reported (Dewey et al 2004, Podell 2004, von Klopmann et al 2007). During the development of ZNS, its electrophysiological and seizure-suppressing effects were studied in kindled cats, and those studies proved its antiepileptic effect in cats (Ito et al 1980, Wada et al 1990). However, no study has been reported regarding the pharmacokinetic and toxicological properties of ZNS in cats.…”

mentioning

confidence: 99%

Pharmacokinetics and toxicity of zonisamide in cats

Hasegawa

Kobayashi

Kuwabara

et al. 2008

Journal of Feline Medicine and Surgery

View full text Add to dashboard Cite

With the eventual goal of making zonisamide (ZNS), a relatively new antiepileptic drug, available for the treatment of epilepsy in cats, the pharmacokinetics after a single oral administration at 10mg/kg and the toxicity after 9-week daily administration of 20mg/kg/day of ZNS were studied in healthy cats. Pharmacokinetic parameters obtained with a single administration of ZNS at 10mg/day were as follows: Cmax=13.1microg/ml; Tmax=4.0h; T(1/2)=33.0h; areas under the curves (AUCs)=720.3microg/mlh (values represent the medians). The study with daily administrations revealed that the toxicity of ZNS was comparatively low in cats, suggesting that it may be an available drug for cats. However, half of the cats that were administered 20mg/kg/day daily showed adverse reactions such as anorexia, diarrhoea, vomiting, somnolence and locomotor ataxia.

show abstract

3-Sulfamoylmethyl-l,2-benzisoxazole, a new type of anticonvulsant drug: Electroencephalographic profile

Cited by 6 publications

References 0 publications

Clinical Experience With Zonisamide Monotherapy and Adjunctive Therapy in Children With Epilepsy at a Tertiary Care Referral Center

Clinical Experience With Zonisamide Monotherapy and Adjunctive Therapy in Children With Epilepsy at a Tertiary Care Referral Center

Polypharmacology of carbonic anhydrase inhibitors

Pharmacokinetics and toxicity of zonisamide in cats

Contact Info

Product

Resources

About