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Zonisamide

Distribution by Scientific Domains
Medical Sciences95%
Distribution within Medical Sciences
Neurology62%
Psychiatry20%

Kinds of Zonisamide

  • adjunctive zonisamide
    		•

    Selected Abstracts

    Preclinical abuse potential assessment of the anticonvulsant zonisamide

    DRUG DEVELOPMENT RESEARCH, Issue 2 2001
    Jenny L. Wiley
    Abstract Zonisamide (Zonegran®) is a broad-spectrum antiepileptic agent that shares some pharmacological properties with other anticonvulsants, including phenytoin, carbamazepine, and valproic acid, but is differentiated from these agents by the ability to significantly block T-type calcium channels. Zonisamide interacts with the ,-amino-butyric acid (GABA) receptor in an allosteric manner, and thus does not modulate GABA receptor effects. However, given the potential of drugs within the latter class for drug abuse in humans, an evaluation of zonisamide for abuse potential is an important component of its potential side-effect profile. In the present study, zonisamide was tested in animal models of the subjective and reinforcing effects of central nervous system (CNS) depressant drugs, e.g., diazepam discrimination in rats and intravenous self-administration in rhesus monkeys, respectively. In addition, zonisamide was evaluated for physical dependence liability in a chronic infusion model using rats. Zonisamide did not substitute for diazepam in rats trained to discriminate 2.5-mg/kg diazepam from vehicle nor was it self-administered by rhesus monkeys experienced in methohexital-reinforced responding. Continuous infusion of zonisamide (400 or 600 mg/kg/day) did not prevent the loss of body weight associated with discontinued pentobarbital infusion. These doses of zonisamide did produce some incomplete attenuation of observable signs of pentobarbital withdrawal, likely due to direct sedative or depressant effects of these high doses. These results suggest that zonisamide would not produce diazepam-like intoxication in humans nor would it likely be subject to abuse when made more widely available. Further, when administered chronically, zonisamide would not be expected to produce physical dependence of the CNS depressant type. Taken together, these results support the prediction that zonisamide would have low abuse liability. Drug Dev. Res. 54:66,74, 2001. © 2001 Wiley-Liss, Inc. [source]

    Contrasting Effects of Zonisamide and Acetazolamide on Amygdaloid Kindling in Rats

    EPILEPSIA, Issue 11 2001
    Koichi Hamada
    Summary: ,Purpose: Zonisamide (ZNS) and acetazolamide (AZM) are two antiepileptic drugs (AEDs) that differ in clinical efficacy. To elucidate the mechanisms of action of these compounds, we investigated their therapeutic and prophylactic effects in rats by using a kindling model of partial epilepsy. Methods: Electrodes were implanted into the left amygdala of adult male Wistar rats. The animals were stimulated at the afterdischarge threshold until five stage 5 seizures were induced. The generalized seizure threshold was then determined. Therapeutic effects were examined in rats manifesting successive convulsions with near-threshold stimulation. To test prophylactic effects, drugs were administered intraperitoneally before daily kindling stimulation until the animal had a stage 5 seizure or reached day 18. Results: ZNS (10,40 mg/kg; n = 6) suppressed kindled seizures in a dose-dependent manner. Repeated administration for 7 days produced tolerance to anticonvulsive effects. AZM (25,200 mg/kg; n = 7) showed limited therapeutic effect, alleviating only the clonic convulsion in stage 5 seizures and reducing afterdischarge duration. Secondary generalization was not significantly suppressed during repeated treatment (50,200 mg/kg; n = 6). ZNS, 25 or 40 mg/kg (n = 8), significantly retarded seizure development; 15.0 or 17.0 daily stimulations were required to produce a stage 5 seizure. AZM, 50,200 mg/kg (n = 6), also retarded seizure development, with 14.0,14.8 stimulations required. Conclusions: ZNS exhibited modest therapeutic and prophylactic effects, whereas AZM showed mainly prophylactic effects. Hypotheses are presented that may explain the mechanisms of action of these drugs. [source]

    Zonisamide Reduces the Increase in 8-Hydroxy-2,-Deoxyguanosine Levels Formed During Iron-Induced Epileptogenesis in the Brains of Rats

    EPILEPSIA, Issue 9 2000
    M. Komatsu
    Summary: Purpose: To examine the change of 8,-hydroxy-2,-deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum. Method: Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats. Results: Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection. Conclusions: These results indicate that the formation of iron-induced epileptogenic foci in rats is related to DNA-damage-induced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts,induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts,induced acute epileptogenesis. [source]

    Chronological Changes of Plasma Homovanillic Acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) Levels in 4 Patients with Temporal Lobe Epilepsy who Developed Psychosis-Like Symptoms (Hallucination and Delusion) During Zonisamide (ZNS) Administration.

    EPILEPSIA, Issue 2000
    Takuya Ueno
    Purpose: Zonisamide (ZNS) is a relatively new antiepileptic drug with an extensive therapeutic spectrum. However, ZNS can produce psychiatric side effects. In this study, we serially measured plasma hoinovaniliic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in 4 patients with epilepsy who developed psychosis-like symptoms (hallucinations and delusions) during ZNS administration. Methods: Subjects comprised 4 patients (3 males and 1 female) with temporal lobe epilepsy ranging in age from 18 to 28 years. Intervals from the start of ZNS administration to the appearance of psychiatric symptoms ranged from 36 to 707 days. Intervals from achievement of the maximal dose to the appearance of psychiatric symptoms ranged from 2 to 240 days. In these 4 patients, the maximal doses of ZNS ranged from 300 to 600 mg/day. In 3 cases, serum ZNS levels were within the effective therapeutic concentration range wlicn syinptoms appeared. However, in 1 case, the serum ZNS level exceeded thc therapeutic level. In all cases, psychiatric symptoms disappeared after ZNS was switched to other antiepileptic drugs and anti-psychotic agents (2-5 mg/day of haloperidol or 10 mg/day of thioridazine) were added. In these cases, we serially measured plasma HVA and MHPG concentrations. Results: Case 1 was a 28-year-old male. Delusions of persecution appeared 190 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 12.7 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.4 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 14.5 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, whereas the MHPG level was slightly increased. Case 2 was an 18-year-old female. Auditory hallucinations appeared 320 days after ZNS first was administered. HVA levels at the appearance of psychiatric symptoms were 9.6- 10.0 nghl and HVA levels at the disappearance of psychiatric symptoms were 5.3,6.1 ng/ml. MHPG levcls at the appearance of psychiatric symptoms were 4.14.2 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.1 ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Case 3 was an 18-year-old male. Delusion of persecution appeared 707 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 10.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ngiml. MHPG levels at the appearance of psychiatric symptoms were 5.3 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.9 ng/ml. When psychiatric symptoms appeared, plasma HVA level was increased, while the MHPG level was slightly increased. Case 4 was a 20-year-old male. Auditory hallucination appeared 36 days after ZNS was administered. HVA levels at the appearance of psychiatric symptoms were 13.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 5.4 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Conclusions: In all patients, the plasma HVA levels at the appearance of psychiatric symptoms was higher than the corresponding level at time of disappearance of psychiatric symptoms. Psychiatric symptoms may have been associated with activation of dopaniine by ZNS. MHPG levels were slightly increased in 2 cases. However, in thc other 2 cases, there were no changes in MHPG. The influence of ZNS on neurotransmitter metabolites should be further investigated in a larger nuniber of patients. [source]

    Zonisamide Prophylaxis in Refractory Pediatric Headache

    HEADACHE, Issue 5 2006
    Ann Pakalnis MD
    Introduction.,Currently, no medications are approved for pediatric headache prophylaxis in the United States. Zonisamide is an antiepileptic drug with preliminary studies suggesting some efficacy in the adult headache population. Methods.,A retrospective chart review was conducted on refractory headache patients in our multidisciplinary Headache Clinic who were treated with zonisamide, an antiepileptic drug, for headache prophylaxis. Records were reviewed for pertinent data including patient history, diagnosis, prior treatment regimens, and zonisamide response, along with headache frequency. Results.,Twelve patients were identified (8 girls); mean age was 13.5 years. Eight of the 12 patients had a positive response to zonisamide with greater than 50% reduction in headaches from pretreatment values. Conclusion.,Zonisamide had some efficacy in headache reduction. It was well tolerated with only minor side effects. Further prospective studies with zonisamide are warranted in refractory pediatric headache patients. [source]

    Zonisamide (Zonegran): a new adjunctive antiepileptic therapy

    PRESCRIBER, Issue 2 2006
    Linda Stephen MRCGP
    The latest antiepileptic drug, Zonisamide (Zonegran), is currently licensed for the adjunctive treatment of partial and secondary generalised seizures in adults. Here, the authors consider its efficacy and safety and also discuss the possibility of the drug having efficacy across a range of seizure types. Copyright © 2006 Wiley Interface Ltd [source]

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

    PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2001
    Masataka Tominaga MD
    Abstract 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 dose-dependently 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. [source]

    Acute treatment of bipolar depression with adjunctive zonisamide: a retrospective chart review

    BIPOLAR DISORDERS, Issue 5 2004
    Claudia F Baldassano
    Background:, This retrospective chart review evaluated the use of zonisamide as adjunctive treatment in patients with bipolar depression. Method:, The charts of outpatients with bipolar I or II disorder treated with adjunctive zonisamide were reviewed. The efficacy of zonisamide was assessed via comparison of physician-rated Global Assessment of Functioning (GAF) and Clinical Global Impression of Severity (CGI-S) Scale scores at baseline and after 6 weeks of therapy using paired t -tests. Patients who scored ,2 on the CGI-S after 6 weeks of zonisamide therapy were considered good responders to zonisamide. Results:, Charts for 12 patients (four men and eight women) with a mean (±SD) age of 39.6 (±7.6) years were evaluated. Patients received a mean (±SD) zonisamide dosage of 236 (±68) mg/day. Mean GAF scores significantly improved from 44.0 at baseline to 59.3 at week 6 (P = 0.05). Mean CGI-S scores improved from 4.54 at baseline to 3.42 at week 6, but the change was not statistically significant. Six patients (50.0%) were considered responders to zonisamide. Four patients discontinued zonisamide therapy, two for an adverse event (sedation) and two for lack of efficacy. Conclusions:, Zonisamide may be a useful adjunctive treatment for some patients with bipolar depression. Conclusions from this study are limited due to its retrospective design. Further investigation of zonisamide in the treatment of bipolar depression is warranted. [source]

    Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010
    S. Dupont
    Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source]

    Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009
    M. Maschio
    Background,, Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). Aim of the study,, To evaluate efficacy and tolerability of ZNS as add-on in BTRE. Methods, We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. Results,, Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%. Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions,, Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions. [source]

    The impact of zonisamide on weight.

    ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009
    A clinical study in 103 patients with epilepsy
    Objective,,, To investigate the impact of zonisamide (ZNS) on body weight in patients with epilepsy. Methods,,, A retrospective chart analysis of weight changes after initiation of ZNS (103 patients; 54 female; age 17,68 years). For 31 patients follow-up data after ZNS-withdrawal were available. Patients were categorized according to body-mass-index (BMI) <20, 20,25, and >25 kg/m2. Results,,, Body weight before ZNS was 78.6 ± 16.0 kg (range 45,120 kg), BMI 26.5 ± 5.2 kg/m2 (range17.6,41.3 kg/m2). Within 13 ± 7.2 months of treatment, mean body weight decreased by ,3.7% ± 9.1%, showing high interindividual variability (,36% to +32%). Weight loss >5% was documented in 35%, weight gain >5% in 14% of patients. Weight loss was more prominent in patients being overweight prior to treatment onset. At the end of follow-up, patients with overweight had decreased by number. Weight changes under ZNS were not correlated to ZNS daily dosage. Following discontinuation of ZNS treatment weight loss proved to be reversible. Conclusion,,, Zonisamide reduced weight in 35% of patients, especially in patients with overweight prior to treatment. Weight loss is reversible following discontinuation of treatment with ZNS. [source]

    Antiepileptic drugs in the preventive treatment of migraine in children and adolescents

    DRUG DEVELOPMENT RESEARCH, Issue 6 2007
    Catello Vollono
    Abstract Migraine prevalence in childhood ranges from 2.7 to 10% causing a significant impact on quality of life. No drugs are currently approved for use in the prevention of pediatric migraine. Antiepileptic drugs such as valproate and topiramate have been approved for the preventive treatment of migraine in adults. The present study aimed at reviewing evidence on the efficacy and safety of antiepileptic drugs in the preventive treatment of migraine in children and adolescents. We searched PubMed from 1988 to May 2007 and reviewed, abstracted, and classified relevant literature. Thirteen studies were reviewed. Data from randomized controlled trials are available only for valproate and topiramate. They show that both topiramate and valproate are effective in reducing headache frequency, intensity, and duration. As for safety and tolerability, topiramate is well tolerated, while there are insufficient data regarding the tolerability of valproate. Open-label or retrospective studies suggest that levetiracetam, zonisamide, and gabapentin are effective, but further evidence is warranted to confirm these data. Drug Dev Res 68:355,359, 2007. © 2007 Wiley-Liss, Inc. [source]

    Preclinical abuse potential assessment of the anticonvulsant zonisamide

    DRUG DEVELOPMENT RESEARCH, Issue 2 2001
    Jenny L. Wiley
    Abstract Zonisamide (Zonegran®) is a broad-spectrum antiepileptic agent that shares some pharmacological properties with other anticonvulsants, including phenytoin, carbamazepine, and valproic acid, but is differentiated from these agents by the ability to significantly block T-type calcium channels. Zonisamide interacts with the ,-amino-butyric acid (GABA) receptor in an allosteric manner, and thus does not modulate GABA receptor effects. However, given the potential of drugs within the latter class for drug abuse in humans, an evaluation of zonisamide for abuse potential is an important component of its potential side-effect profile. In the present study, zonisamide was tested in animal models of the subjective and reinforcing effects of central nervous system (CNS) depressant drugs, e.g., diazepam discrimination in rats and intravenous self-administration in rhesus monkeys, respectively. In addition, zonisamide was evaluated for physical dependence liability in a chronic infusion model using rats. Zonisamide did not substitute for diazepam in rats trained to discriminate 2.5-mg/kg diazepam from vehicle nor was it self-administered by rhesus monkeys experienced in methohexital-reinforced responding. Continuous infusion of zonisamide (400 or 600 mg/kg/day) did not prevent the loss of body weight associated with discontinued pentobarbital infusion. These doses of zonisamide did produce some incomplete attenuation of observable signs of pentobarbital withdrawal, likely due to direct sedative or depressant effects of these high doses. These results suggest that zonisamide would not produce diazepam-like intoxication in humans nor would it likely be subject to abuse when made more widely available. Further, when administered chronically, zonisamide would not be expected to produce physical dependence of the CNS depressant type. Taken together, these results support the prediction that zonisamide would have low abuse liability. Drug Dev. Res. 54:66,74, 2001. © 2001 Wiley-Liss, Inc. [source]

    The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet

    EPILEPSIA, Issue 8 2009
    Peter F. Morrison
    Summary It is unknown if any particular anticonvulsants modify the likelihood of seizure reduction when used in combination with the ketogenic diet (KD). A retrospective study was performed of 217 consecutive children who started the KD from 2000,2007. Patients included did not have any changes to their anticonvulsant dose. Efficacy data at 3 months on the KD were analyzed with respect to the six most frequently used anticonvulsants in this cohort. A total of 115 patients were included. Children receiving phenobarbital in combination with the KD were significantly less likely to have a >50% seizure reduction (p = 0.003). Conversely, those receiving zonisamide in combination with the KD at onset were more likely to have a >50% reduction (p = 0.04). These results provide practical information to clinicians who are treating children receiving both the KD and anticonvulsants. [source]

    Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society

    EPILEPSIA, Issue 5 2004
    Jacqueline A. French
    Summary: Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. Results: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary. [source]

    Zonisamide Reduces the Increase in 8-Hydroxy-2,-Deoxyguanosine Levels Formed During Iron-Induced Epileptogenesis in the Brains of Rats

    EPILEPSIA, Issue 9 2000
    M. Komatsu
    Summary: Purpose: To examine the change of 8,-hydroxy-2,-deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum. Method: Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats. Results: Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection. Conclusions: These results indicate that the formation of iron-induced epileptogenic foci in rats is related to DNA-damage-induced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts,induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts,induced acute epileptogenesis. [source]

    Developmental and Therapeutic Pharmacology of Antiepileptic Drugs

    EPILEPSIA, Issue 2000
    Hisao Miura
    Summary: We investigated the clinical effects and plasma levels of zonisamide (ZNS) in children with cryptogenic localization-related epilepsies. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long as compared with that of other common antiepileptic drugs. The peak-to-trough plasma level ratios during a day were as small as 1.28 ± 0.15 in children taking a daily dose of 8 mg/kg of ZNS once a day as a single drug. The plasma level (,g/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels both increased with advancing age, but the peak-to-trough plasma level ratios were maintained almost uniformly throughout the pediatric age period. A wide range of the plasma levels was associated with complete freedom from seizures. The range of the plasma levels in patients who did not respond to ZNS was higher than that in the controlled group. However, the clinical effects of ZNS were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15,40 ,g/ml. Any patient who receives polytherapy is at risk to develop 1 or more drug interactions. Concurrent administration of carbamazepine (CBZ) decreases plasma concentrations of ZNS. However, ZNS does not alter plasma concentrations of CBZ or its primary metabolite, carbamazepine-10,11-epoxide (CBZ-E). It is evident that the concurrent administration of lamotrigine (LTG) affects plasma concentrations of CBZ-E, while plasma CBZ levels remain unaltered. However, the effect of LTG on plasma concentrations of CBZ-E is small, and none of the study patients showed toxic plasma concentrations of CBZ-E or associated clinical toxicity. Drug-protein binding interactions are another source of side effects. A simultaneous administration of valproic acid increases the total plasma CBZ-E levels relative to the CBZ dose associated with the raised free fractions of CBZ and CBZ-E. The high free plasma concentrations of CBZ-E above 1.5 ,g/ml may be responsible for the side effects. [source]

    Neuromodulators for Migraine Prevention

    HEADACHE, Issue 4 2008
    Robert Kaniecki MD
    Migraine is a debilitating condition characterized by a cycle of painful headaches and headache-related symptoms interspersed with periods of worry, distress, and apprehension. The negative impact of migraine on patient functioning, workplace productivity, and other daily activities has been demonstrated through the use of a variety of clinician- and patient-reported assessment tools, including the Migraine-Specific Questionnaire and the Migraine Disability Assessment questionnaire. In addition to considering the frequency and severity of migraine, clinicians need to encourage more open dialogue with their patients about the impact of this disorder on daily activities and productivity. Only then can the most appropriate course of treatment be determined. Appropriately prescribed acute and preventive therapies should break the cycle of migraine and improve the daily activities of patients with this chronic condition. Divalproex sodium and topiramate are neuromodulators that are approved by the US Food and Drug Administration (FDA) for the prophylaxis (prevention) of migraine headache in adults. Non-FDA-approved neuromodulators sometimes used in the management of migraine headache include gabapentin, lamotrigine, levetiracetam, and zonisamide. All medications need to be titrated, and treatment-related adverse events need to be managed appropriately. Preventive medications should be taken for at least 2-3 months to ascertain their therapeutic effect. [source]

    Zonisamide Prophylaxis in Refractory Pediatric Headache

    HEADACHE, Issue 5 2006
    Ann Pakalnis MD
    Introduction.,Currently, no medications are approved for pediatric headache prophylaxis in the United States. Zonisamide is an antiepileptic drug with preliminary studies suggesting some efficacy in the adult headache population. Methods.,A retrospective chart review was conducted on refractory headache patients in our multidisciplinary Headache Clinic who were treated with zonisamide, an antiepileptic drug, for headache prophylaxis. Records were reviewed for pertinent data including patient history, diagnosis, prior treatment regimens, and zonisamide response, along with headache frequency. Results.,Twelve patients were identified (8 girls); mean age was 13.5 years. Eight of the 12 patients had a positive response to zonisamide with greater than 50% reduction in headaches from pretreatment values. Conclusion.,Zonisamide had some efficacy in headache reduction. It was well tolerated with only minor side effects. Further prospective studies with zonisamide are warranted in refractory pediatric headache patients. [source]

    Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

    JOURNAL OF SMALL ANIMAL PRACTICE, Issue 3 2007
    T. Von Klopmann
    Objectives: Investigation of the efficacy of zonisamide as an add-on therapy in dogs with refractory epilepsy. Methods: Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment. Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add-on therapy. The study time period was extended by up to 17 months to evaluate long-term outcome. Results: Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add-on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months). Clinical Significance: In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs. [source]

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

    PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2001
    Masataka Tominaga MD
    Abstract 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 dose-dependently 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. [source]

    Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizure-susceptible EL mice

    PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2001
    Wataru Hashiguchi MD
    Abstract To investigate changes of nitric oxide (NO) productions and zonisamide (ZNS) concentrations in the brain of seizure-susceptible EL mice given caffeine orally, mice were given caffeine (600 ,g/mL) solution ad libitum as a drinking fluid for 1,3 weeks. Nitric oxide production in the brain was determined by measuring levels of nitrite plus nitrate (NOx). The brain NOx levels of mice treated with caffeine for 3 weeks were significantly higher than the control. Seizures in mice treated with caffeine for 2 and 3 weeks were not suppressed by ZNS at a dose of 75 mg/kg. Serum ZNS concentrations of mice with caffeine intake for 1,3 weeks were higher than in untreated mice. Conversely, brain ZNS concentrations of mice with caffeine intake for the same periods were significantly lower than in untreated mice. These results suggested that caffeine influenced brain NO production and ZNS concentrations in the seizure susceptibility of EL mice. [source]

    Neuroprotective effects of zonisamide target astrocyte

    ANNALS OF NEUROLOGY, Issue 2 2010
    Masato Asanuma MD
    Objective Recent double-blind, controlled trials in Japan showed that the antiepileptic agent zonisamide (ZNS) improves the cardinal symptoms of Parkinson's disease. Glutathione (GSH) exerts antioxidative activity through quenching reactive oxygen species and dopamine quinone. GSH depletion within dopaminergic neurons impairs mitochondrial complex I activity, followed by age-dependent nigrostriatal neurodegeneration. This study examined changes in GSH and GSH synthesis-related molecules, and the neuroprotective effects of ZNS on dopaminergic neurodegeneration using 6-hydroxydopamine,injected hemiparkinsonian mice brain and cultured neurons or astrocytes. Methods and Results ZNS increased both the cell number and GSH levels in astroglial C6 cells, but not in dopaminergic neuronal CATH.a cells. Repeated injections of ZNS (30mg/kg intraperitoneally) for 14 days also significantly increased GSH levels and S100,-positive astrocytes in mouse basal ganglia. Repeated ZNS injections (30mg/kg) for 7 days in the hemiparkinsonian mice increased the expression of cystine/glutamate exchange transporter xCT in activated astrocytes, which supply cysteine to neurons for GSH synthesis. Treatment of these mice with ZNS also increased GSH levels and completely suppressed striatal levodopa,induced quinone formation. Reduction of nigrostriatal dopamine neurons in the lesioned side of hemiparkinsonian mice was significantly abrogated by repeated injections of ZNS with or without adjunctive levodopa starting 3 weeks after 6-hydroxydopamine lesioning. Interpretation These results provide new pharmacological evidence for the effects of ZNS. ZNS markedly increased GSH levels by enhancing the astroglial cystine transport system and/or astroglial proliferation via S100, production or secretion. ZNS acts as a neuroprotectant against oxidative stress and progressive dopaminergic neurodegeneration. ANN NEUROL 2010;67:239,249 [source]

    Simultaneous determination of lamotrigine, zonisamide, and carbamazepine in human plasma by high-performance liquid chromatography

    BIOMEDICAL CHROMATOGRAPHY, Issue 3 2007
    Elizabeth Greiner-Sosanko
    Abstract A high-performance liquid chromatography assay with ultraviolet detection was developed for the simultaneous determination of the anti-epileptic drugs lamotrigine, carbamazepine and zonisamide in human plasma and serum. Lamotrigine, carbamazepine, zonisamide and the internal standard chloramphenicol were extracted from serum or plasma using liquid,liquid extraction under alkaline conditions into an organic solvent. The method was linear in the range 1,30 µg/mL for lamotrigine, 2,20 µg/mL for carbamazepine, and 1,40 µg/mL for zonisamide. Within- and between-run precision studies demonstrated coefficient of variation <10% at all tested concentrations. Other anti-epileptic medications tested did not interfere with the assay. The method is appropriate for determining lamotrigine, carbamazepine and zonisamide serum or plasma concentrations for therapeutic monitoring. Copyright © 2007 John Wiley & Sons, Ltd. [source]

    Acute treatment of bipolar depression with adjunctive zonisamide: a retrospective chart review

    BIPOLAR DISORDERS, Issue 5 2004
    Claudia F Baldassano
    Background:, This retrospective chart review evaluated the use of zonisamide as adjunctive treatment in patients with bipolar depression. Method:, The charts of outpatients with bipolar I or II disorder treated with adjunctive zonisamide were reviewed. The efficacy of zonisamide was assessed via comparison of physician-rated Global Assessment of Functioning (GAF) and Clinical Global Impression of Severity (CGI-S) Scale scores at baseline and after 6 weeks of therapy using paired t -tests. Patients who scored ,2 on the CGI-S after 6 weeks of zonisamide therapy were considered good responders to zonisamide. Results:, Charts for 12 patients (four men and eight women) with a mean (±SD) age of 39.6 (±7.6) years were evaluated. Patients received a mean (±SD) zonisamide dosage of 236 (±68) mg/day. Mean GAF scores significantly improved from 44.0 at baseline to 59.3 at week 6 (P = 0.05). Mean CGI-S scores improved from 4.54 at baseline to 3.42 at week 6, but the change was not statistically significant. Six patients (50.0%) were considered responders to zonisamide. Four patients discontinued zonisamide therapy, two for an adverse event (sedation) and two for lack of efficacy. Conclusions:, Zonisamide may be a useful adjunctive treatment for some patients with bipolar depression. Conclusions from this study are limited due to its retrospective design. Further investigation of zonisamide in the treatment of bipolar depression is warranted. [source]

    Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010
    S. Dupont
    Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source]

    Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009
    M. Maschio
    Background,, Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). Aim of the study,, To evaluate efficacy and tolerability of ZNS as add-on in BTRE. Methods, We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. Results,, Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%. Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions,, Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions. [source]

    The impact of zonisamide on weight.

    ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009
    A clinical study in 103 patients with epilepsy
    Objective,,, To investigate the impact of zonisamide (ZNS) on body weight in patients with epilepsy. Methods,,, A retrospective chart analysis of weight changes after initiation of ZNS (103 patients; 54 female; age 17,68 years). For 31 patients follow-up data after ZNS-withdrawal were available. Patients were categorized according to body-mass-index (BMI) <20, 20,25, and >25 kg/m2. Results,,, Body weight before ZNS was 78.6 ± 16.0 kg (range 45,120 kg), BMI 26.5 ± 5.2 kg/m2 (range17.6,41.3 kg/m2). Within 13 ± 7.2 months of treatment, mean body weight decreased by ,3.7% ± 9.1%, showing high interindividual variability (,36% to +32%). Weight loss >5% was documented in 35%, weight gain >5% in 14% of patients. Weight loss was more prominent in patients being overweight prior to treatment onset. At the end of follow-up, patients with overweight had decreased by number. Weight changes under ZNS were not correlated to ZNS daily dosage. Following discontinuation of ZNS treatment weight loss proved to be reversible. Conclusion,,, Zonisamide reduced weight in 35% of patients, especially in patients with overweight prior to treatment. Weight loss is reversible following discontinuation of treatment with ZNS. [source]

    Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy

    ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008
    S. J. Wroe
    Objectives,,, To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice. Materials and methods,,, Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice. Results,,, An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom. Conclusions,,, Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy. [source]

    Comparison of the efficacy and tolerability of new antiepileptic drugs: what can we learn from long-term studies?

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2006
    G. Zaccara
    Objective,,, A review of long-term open-label studies was performed with the aim of detecting differences in efficacy and/or tolerability of new antiepileptic drugs (AEDs). Methods,,, From more than 500 open studies conducted to evaluate the efficacy and tolerability of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB), tiagabine (TGB), topiramate (TPM) or zonisamide (ZNS), we selected all studies that reported or allowed us to calculate the number of patients who achieved seizure freedom for 6 months and/or the number of patients withdrawing for adverse effects and/or the number or percentage of patients continuing treatment after 1 year. Results,,, No studies were found in which this information was available for OXC, PGB, TGB or ZNS. The number of patients who achieved seizure freedom for 6 months was reported in four studies each for GBP and TPM, five studies for LTG, and eight studies for LEV. The best efficacy profile using this end point was found for LEV, followed by TPM, LTG, and GBP. Twenty-two studies reported the number of patients withdrawing due to adverse effects. LEV was the best-tolerated AED, a little ahead of LTG, and significantly better than GBP or TPM . TPM was by far the least well-tolerated drug. Information concerning patients continuing treatment after 1 year was reported in two GBP studies, two TPM studies, six LEV studies and five LTG studies. GBP had a very low retention rate (between 20% and 25% of patients continued the drug), while TPM and LTG had a retention rate of 40,60% and LEV had a retention rate of 60,75%. Conclusion,,, One limitation of these rankings is that their statistical value is limited because of the indirect nature of the comparisons. Anyhow, this review covers the main studies published thus far on this subject and provides full updated information on the current literature about these drugs. [source]