Effects of Zonisamide (AD‐810) on Tungstic Acid Gel‐Induced Thalamic Generalized Seizures and Conjugated Estrogen‐Induced Cortical Spike‐Wave Discharges in Cats

Ito, Tsugutaka; Hori, Misako; Kadokawa, Toshiaki

doi:10.1111/j.1528-1157.1986.tb03555.x

Cited by 27 publications

(8 citation statements)

References 10 publications

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“…The effects of ZNS in the electro-and chemoshock seizure tests were similar to those observed with PHT and CBZ (29,49,50), suggesting that ZNS, like PHT and CBZ, exerts an anticonvulsant effect by inhibiting the spread or propagation of seizures. This observation was supported by electroencephalographic studies (30,31) which showed that ZNS restricted the spread of cortical seizures evoked by electrical stimulation and prevented cortical focal spikes elicited by cortical freezing from developing into generalized seizures in cats. ZNS suppressed focal seizure activity in the cat cortex due to electrical stimulation and produced a dose-related significant increase in afterdischarge threshold (103).…”

Section: Anticonvulsant Propertiesmentioning

confidence: 66%

“…ZNS was effective against interictal spiking activity within cortical foci. ZNS suppressed or abolished spikes occurring interictally between recurrent episodes of generalized seizures and reduced the frequency and amplitude of focal spikes in the cat cortex by freezing (30) or by application of conjugated estrogens (31). These effects, not observed with PHT, PB, or trimethadione, would be to suppress activity within the focus, especially in the cortex.…”

Section: Anticonvulsant Propertiesmentioning

confidence: 99%

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Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy

1998

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Section: Anticonvulsant Propertiesmentioning

confidence: 66%

Section: Anticonvulsant Propertiesmentioning

confidence: 99%

Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy

1998

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“…Moreover, ZNS suppresses tungstic acid gel-induced thalamic generalized seizures and conjugated estrogen-induced cortical spike-wave discharges in cats (147), providing additional experimental support for its efficacy in primary generalized epilepsies.…”

Section: Zonisamidementioning

confidence: 85%

The Pharmacologic Basis of Antiepileptic Drug Action

1999

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Summary:The development of medications used in the treatment of epilepsy has accelerated over the past decade, and has benefited from a parallel growth in our knowledge of the basic mechanisms underlying neuronal excitability and synchronization. This understanding of the pharmacologic basis of antiepileptic drug (AED) action has, in large part, arisen from recent advances in cellular and molecular biology, coupled with avenues of drug discovery that have departed somewhat from the largely empiric approaches of the past. Physicians now have available to them an ever-growing armentarium of AEDs, neTherapy with antiepileptic drugs (AEDs) remains the mainstay of treatment of patients with epilepsy. Before the Victorian era, therapeutic approaches to epilepsy were largely based on superstition and charlatanism. The first demonstrably effective chemotherapy relied on the use of nonspecific depressants of the central nervous system. Sir Charles Locock introduced bromides in the mid-nineteenth century for the treatment of catamenial epilepsies, and phenobarbital (PB) was adopted in 1912 after the observations of Hauptmann (l), who used that compound to sedate a ward of noisy psychiatric patients and those with epilepsy during the night. Introduction of more specific AEDs for clinical application followed the availability of the first animal-seizure model: the maximal electroshock (MES) model (2). The history of AED design has recently been reviewed in some detail (3).The relation of the human epilepsies to the animal models commonly used for AED development, and to the cellular membrane physiology underlying neuronal excitability, continues to be an imperfect one (Fig. 1) cessitating a firmer appreciation of their mechanisms of action if more rational approaches toward both clinical application and research are to be adopted. An important example in this regard is the concept of rational polypharmacy for patients with epilepsy who are refractory to monotherapy. This review summarizes our current understanding of the molecular targets of clinically significant AEDs, comparing and contrasting their differing mechanisms of action. Key Words: Antiepileptic drug-AED-Anticonvulsant-Mechanism-%-zure-Epilepsy-Ion channel.threshold pentylenetetrazol (PTZ) test in mice (see Table 1) have been carefully standardized (4). The MES model has served to identify AEDs that are functionally similar to phenytoin (PHT), and most of these compounds display in common the ability to inactivate voltage-dependent Na+ channels in a use-dependent fashion. Such compounds suppress sustained repetitive firing in cultured neurons. Activity in this model seems highly predictive of the ability of those AEDs to protect against partial and secondarily generalized tonic-clonic seizures (Fig. 2). Carbamazepine (CBZ), as well as several newer agents such as felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), and topiramate (TPM), fit this model of AED activity. Some of these (i.e., PHT, CBZ, LTG) may also attenuate the release of excitatory neurotransmi...

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“…Clinical and animal tests have shown that the pharmacologic profile of ZNS resembles those of phenytoin (PHT) and carbamazepine (CBZ) 31 . Phenytoin and CBZ displace batrachotoxinin from specific binding sites related to the sodium channels of mammalian neurons, and may exert effects on sodium action potentials by acting at this molecular site 5 .…”

Section: Discussionmentioning

confidence: 99%

Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide

Tominaga

Nagatomo

Uchida

et al. 2001

Psychiatry Clin Neurosci

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The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dosedependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.

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Effects of Zonisamide (AD‐810) on Tungstic Acid Gel‐Induced Thalamic Generalized Seizures and Conjugated Estrogen‐Induced Cortical Spike‐Wave Discharges in Cats

Cited by 27 publications

References 10 publications

Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy

Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy

The Pharmacologic Basis of Antiepileptic Drug Action

Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide

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