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Sample records for anticonvulsants

  1. Anticonvulsants.

    Science.gov (United States)

    Hillebrand, Marc; Young, John L.

    1994-01-01

    Anticonvulsants have gained recognition for their beneficial effect in the treatment of aggressive behavior, particularly carbamazepine. Empirical studies of the effectiveness of anticonvulsants in decreasing aggression are reviewed and evaluated, and cost-benefit factors related to the use of anticonvulsants are evaluated. A protocol for the…

  2. Anticonvulsants for tinnitus (Review)

    NARCIS (Netherlands)

    Hoekstra, C.E.; Rynja, S.P.; Zanten, G.A.; Rovers, M.M.

    2011-01-01

    BACKGROUND: Tinnitus is the perception of sound or noise in the absence of an external or internal acoustic stimulation. It is a common and potentially distressing symptom for which no adequate therapy exists. OBJECTIVES: To assess the effectiveness of anticonvulsants in patients with chronic tinnit

  3. Studies on anticonvulsant agents. Achievements and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Sh; Shukla, Sh; Pandey, D; Srivastava, R S

    2011-02-28

    The data published over the past 15 years on the search for newer anticonvulsant drugs are generalized. Pyrrolidinedione, quinazolinone, xanthone, hydrazine and thiadiazole derivatives manifesting anticonvulsant activity in model in vivo tests in rodents are considered.

  4. Anticonvulsant activity of bioflavonoid gossypin

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    Duraisami Rasilingam

    2009-03-01

    Full Text Available The anticonvulsant activity of gossypin was investigated by studying the effects on seizures induced by pentelentetrazole, strychnine and maximal electroshock convulsive methods in mice. Gossypin (10 and 20 mg/kg significantly reduced the duration of convulsion in tonic seizure induced by pentelenetetrazole (95 mg/kg, intraperitoneally. Gossypin (20 mg/kg p.o significantly reduced the tonic extensor convulsion induced by strychnine and maximum electroshock-induced convulsions. The data obtained suggest that gossypin have anticonvulsant property and may probably be affecting both GABA aminergic and glycine inhibitory mechanism.

  5. Succinimides: Synthesis, properties and anticonvulsant activity

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    Banjac Nebojša

    2011-01-01

    Full Text Available Succinimide is a cycle imide of succinic acid that is present in numerous biologically active compounds including anticonvulsants, antitremor, anti-Parkinson`s agents. This paper describes different ways of synthesis of succinimide-derivatives their physical properties and reactivity. Also, the most widely used succinimide anticonvulsants and the analysis of structure-activity relationships of anticonvulsant drugs in terms of lipophilicity and hydrogen bonding are presented here.

  6. Anticonvulsant Drugs for Nerve Pain, Bipolar Disorder and Fibromyalgia

    Science.gov (United States)

    Anticonvulsant Drugs for Nerve Pain, Bipolar Disorder &Fibromyalgia: Choosing What’sRight for You What are anticonvulsant drugs? Anticonvulsants are drugs used to treat seizures. They are also used to treat bipolar ...

  7. Lactation studies of anticonvulsants : A quality review

    NARCIS (Netherlands)

    van der Meer, Douwe H.; Wieringa, Andre; Wegner, Ilse; Wilffert, Bob; Ter Horst, Peter G.J.

    2015-01-01

    AIM: The aim of this review was to investigate the quality of the current literature on the transfer of anticonvulsants to breast milk to provide an overview of which anticonvulsants are in need of further research. METHODS: We reviewed the quality of the available lactation studies for 19 anticonvu

  8. Concurrent Anticonvulsant/Ketogenic Diet Efficacy

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    J Gordon Millichap

    2009-09-01

    Full Text Available Researchers at the Johns Hopkins Hospital, Baltimore, studied retrospectively the comparative efficacy of six most frequently used anticonvulsants when employed in combination with the ketogenic diet (KD for treatment of 115 children with epilepsy.

  9. A teratological evaluation of anticonvulsant drugs.

    Science.gov (United States)

    Lakos, P; Czeizel, E

    1977-01-01

    Reviewing the important teratological data on anticonvulsants, the Hungarian experiences are reported. In the Hungarian Congenital Malformation Register use of the anticonvulsants diazepam and phenobarbiturates during pregnancy was determined in infants delivered with cleft lip with or without cleft palate, posterior cleft palate and, as a control, anencephaly and spina bifida. The teratogenic effect of diphenyl-hydantoin was confirmed, while that of diazepam and phenobarbital was not supported.

  10. Natural products as potential anticonvulsants: caffeoylquinic acids.

    Science.gov (United States)

    Kim, Hyo Geun; Oh, Myung Sook

    2012-03-01

    Current anticonvulsant therapies are generally directed at symptomatic treatment by suppressing excitability within the brain. Consequently, they have adverse effects such as cognitive impairment, dependence, and abuse. The need for more effective and less toxic anticonvulsants has generated renewed interest in natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are naturally occurring phenolic acids that are distributed widely in plants. There has been increasing interest in the biological activities of CQs in diseases of the central nervous system. In this issue, Nugroho et al. give evidence for the anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt. They optimized the extract solvent conditions, resulting in high levels of CQs and peroxynitrite-scavenging activity. Then, they investigated the sedative and anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed by onset time, tonic extent, and mortality. They suggested that the CQ-rich extract from A. glehni has potential for treating convulsions. This report provides preclinical data which may be used for the development of anticonvulsants from natural products.

  11. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    Science.gov (United States)

    Brown, Shannon C.

    2017-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal multiorgan drug reaction that presents with various cutaneous eruptions. There is a genetic predisposition to such reactions. We present a young woman with AHS due to carbamazepine that presented as an atypical erythema multiforme with elevated liver enzymes. PMID:28127149

  12. Prophylactic Anticonvulsants in patients with brain tumour

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, P.A. [Depts. of Oncology and Clinical Neurosciences, Univ. of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada); Weaver, S. [Depts. of Neurology and Medicine, Albany Medical College, Albany, New York (United States); Fulton, D. [Dept. of Radiation Oncology, Cross Cancer Institute and Dept. of Medicine/Neurology, Univ. of Alberta, Edmonton, Alberta (Canada)

    2003-05-01

    We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need {>=}900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

  13. Anticonvulsant and hypnotic effects of amiodarone

    Institute of Scientific and Technical Information of China (English)

    Gunnur OZBAKIS-DENGIZ; Aysegul BAKIRCI

    2009-01-01

    Amiodarone hydrochloride is a potent anti-arrhythmic agent, known as a multiple ion-channel blocker in the heart.Although it has been detected in the rat brain, there are no data related to its central nervous system (CNS) effects. In this study, we evaluated anticonvulsant and hypnotic effects of amiodarone. Convulsions were induced by phentylenetetrazole (PTZ) (100 mg/kg) or caffeine (300 mg/kg) in mice. In both models, amiodarone prolonged both latency period and time to death, and acted as an anticonvulsant drug. It was found to be more effective in the PTZ model than in the caffeine model; none of the animals treated with 150 mg/kg dose amiodarone had died in the PTZ model. For hypnotic effect, sleeping was induced with pentobarbital (35 mg/kg) in rats. Amiodarone dose-dependently increased the sleeping time (677.7%~725.9%). In the sleeping test, all rats in 200 mg/kg amiodarone group died. In conclusion, anticonvulsant and hypnotic effects of amiodarone have shown the depressant effects on CNS. These effects may be dependent on its pharmacological properties.

  14. Prophylactic antibiotics and anticonvulsants in neurosurgery.

    Science.gov (United States)

    Ratilal, B; Sampaio, C

    2011-01-01

    The prophylactic administration of antibiotics to prevent infection and the prophylactic administration of anticonvulsants to prevent first seizure episodes are common practice in neurosurgery. If prophylactic medication therapy is not indicated, the patient not only incurs the discomfort and the inconvenience resulting from drug treatment but is also unnecessarily exposed to adverse drug reactions, and incurs extra costs. The main situations in which prophylactic anticonvulsants and antibiotics are used are described and those situations we found controversial in the literature and lack further investigation are identified: anticonvulsants for preventing seizures in patients with chronic subdural hematomas, antiepileptic drugs for preventing seizures in those suffering from brain tumors, antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures, and antibiotic prophylaxis for the surgical introduction of intracranial ventricular shunts.In the following we present systematic reviews of the literature in accordance with the standard protocol of The Cochrane Collaboration to evaluate the effectiveness of the use of these prophylactic medications in the situations mentioned. Our goal was to efficiently integrate valid information and provide a basis for rational decision-making.

  15. Comparison of anticonvulsant effects of clorazepate dipotassium and diazepam. Four week anticonvulsant study in Rhesus monkeys.

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    Plotnikoff, N P; O'Brien, G S

    1974-02-01

    Clorazepate dipotassium and diazepam were administered daily for the first 5 days of each week to Rhesus monkeys at equimolar doses and challanged once a week with a convulsant dose of pentylenetetrazol. Clorazepate exhibited sustained anticonvulsant activity throughout the second, third, and fourth weeks while diazepam was effective only during the second and third weeks.

  16. Anticonvulsant Effect of Drosera burmannii Vahl

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    B Hema

    2009-09-01

    Full Text Available Summary: The antiepileptic activity of the alcoholic and aqueous extracts of the whole plant of Drosera burmannii was examined against pentylenetetrazole (PTZ induced seizures in mice. Acute toxicity studies were carried out to evaluate the drug’s toxicity and to determine the minimum lethal dose of the drug extracts, using swiss albino mice. It was found that alcoholic and aqueous extracts up to a dose of 3000mg/kg body weight, did not show any toxic manifestations or death. In PTZ induced seizures, the administration of Drosera burmannii alcoholic extract at a dose  of 500 mg/kg 1 h prior to the injection of PTZ, significantly (p<0.01 delayed the onset of convulsions. Neither alcoholic nor aqueous extracts at the dose of 300 mg/kg body weight could exert any significant protective effect on PTZ induced convulsions. Diazepam in a dose of 4mg/ kg, totally abolished the episodes of convulsions. Alcoholic extract at the dose level of 500 mg/kg body weight showed significant antiepileptic activity.   Industrial relevance: Convulsion has now become the most serious disorder, which accounts for about 1% of the world’s burden of diseases. A number of synthetic anticonvulsant drugs are available in the market. However, the side effects and the drug interactions are major restrictions in its clinical utility. Herbal medicines are widely used due to their therapeutic efficacy coupled with least side effects, which initiate the scientific research regarding the anticonvulsant activity. The present study will help the industry to develop herbal medicine in the treatment of convulsion with fewer side effects. In future the development of formulation by these plant constituents will give good anti-convulsion drug at lower cost.

  17. [Ketamine--anticonvulsive and proconvulsive actions].

    Science.gov (United States)

    Kugler, J; Doenicke, A

    1994-11-01

    Animal experimentation has revealed that ketamine has anticonvulsive properties. Changes in the EEG have also been reported in animals; these have been designated non-convulsive generalized electrographic seizures because of their similarities to epileptiform potentials, even though there are no recognizable signs of seizures. The cataleptic condition of the cats in which these changes were observed led to the conclusion that ketamine could cause petit mal seizures, which took the course of petit mal status. Ketamine was therefore also seen as a dangerous anaesthetic agent predisposing to convulsions, the use of which could lead to status epilepticus and irreversible brain damage. These conflicts of opinion should be resolved, as they are based on various misconceptions. (1) The terminology used for epilepsy by specialized clinicians is not always correctly applied in the context of animal experimentation. (2) The activation of epileptiform potentials in the EEG of animals cannot be interpreted as a reliable sign of epileptogenic efficiency in humans. (3) Too little regard is paid to the different actions of anaesthetic agents in various sites of the brain, at different doses and with different routes of administration. (4) The statistical significance and biological relevance of the study results are inadequate because the numbers of observations are too small. Epileptologists regret the insufficiency of animal models as paradigma for the study of efficiency of antiepileptic drugs in humans. The degree by which extensor spasms in the front paw of Gerbils of rats induced by pentylentetrazol or electric current are reduced after application of an anticonvulsive drug is no reliable measure of its anticonvulsive effect in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Anticonvulsant activity of Bacopa monniera in rodents

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    Darpan Kaushik

    2009-12-01

    Full Text Available Bacopa monnieri (L, belonging to the Scrophulariaceae family and commonly known as Brahmi, is well known in India for its CNS activity but its neuropharmacological effect has not yet been explored. In the present study, the antiepileptic effects of the plant were investigated. The ethanolic extract of Bacopa monniera was tested for anticonvulsant activity in albino rats, using different convulsive models. The ethanolic extract of leaves produced significant anticonvulsant activity for all the different models studied. The present study shows a probable mechanism of action similar to that of benzodiazepines (GABA agonist. Thus, these results emphasize the need to diversify by using alternative therapeutic approaches pertaining to herbal medicine, where a single easily available plant may provide solutions to several therapeutic challenges, as observed in the anticonvulsant action of ethanolic extract of B. monniera.Bacopa monniera, da família Scrophulariaceae, e comumente denominada Brahmi, é bem conhecida na Índia por sua atividade no Sistema Nervoso Central, mas seu efeito neurofarmacológico não foi, ainda, explorado. No presente estudo, investigaram-se os efeitos antiepilépticos da planta. O extrato etanólico da Bacopa monniera foi testado quanto à atividade anticonvulsivante em ratos albinos, utilizando-se diferentes modelos de convulsão. O extrato etanólico das folhas produziu atividade anticonvulsivante significativa para todos os diferentes modelos estudados. O presente estudo mostra provável mecanismo de ação semelhante ao dos benzodiazepínicos (agonista do GABA. Assim sendo, esses resultados enfatizam a necessidade de diversificar, utilizando-se abordagens terapêuticas alternativas da medicina natural, em que uma planta facilmente disponível pode fornecer soluções para vários desafios terapêuticos, como o observado na ação anticonvulsivante do extrato etanólico de Bacopa monniera.

  19. Anticonvulsant mechanisms of piperine, a piperidine alkaloid.

    Science.gov (United States)

    Mishra, Awanish; Punia, Jasmine Kaur; Bladen, Chris; Zamponi, Gerald W; Goel, Rajesh Kumar

    2015-01-01

    Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na(+) and Ca(2+) channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na(+) channels. Together, our data suggest Na(+) channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.

  20. Coumarin incorporated triazoles: a new class of anticonvulsants.

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    Bhat, Mashooq A; Al-Omar, Mohammed A

    2011-01-01

    A series of coumarin incorporated 1,2,4- triazole compounds (1-14) were evaluated for their possible anticonvulsant and neurotoxic properties, log P values, pharmacophoric mapping and three dimensional structure analysis. Compound (6) with para-fluoro substitution showed significant anticonvulsant activity.

  1. Anticonvulsant profile of nardostachys jatamansi roots in albino rats

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    Purushotham K.

    2016-06-01

    Conclusions: The anticonvulsant activity of ethanolic extract of nardostachys jatamansi roots was less when compared to Sodium Valproate in Maximal Electro Shock model. Whereas, in Pentylenetetrazole induced seizure model, anticonvulsant activity of ethanolic extract of nardostachys jatamansi roots was comparable to sodium valproate. [Int J Basic Clin Pharmacol 2016; 5(3.000: 758-762

  2. Anticonvulsant medications: an iatrogenic cause of tic disorders.

    Science.gov (United States)

    Burd, L; Kerbeshian, J; Fisher, W; Gascon, G

    1986-06-01

    A review of the relationship between anticonvulsant medications and tics is presented. Data on 5 patients in whom anticonvulsants, either caused tics or exacerbated existing tic disorders is discussed. Discontinuation of the medication resulted in a decrease in the frequency of tickings in all patients. The effects of anticonvulsants on the reticular system are discussed. It is felt that it may be important for clinicians to consider carefully the use of barbiturate anticonvulsants, especially phenobarbital, in children with tics or a family history of tics. Tic disorders caused or exacerbated by exposure to anticonvulsant medications appear to be more common than previously reported, and in some patients the tics may not remit with discontinuation of the medication.

  3. Is bioavailability altered in generic versus brand anticonvulsants?

    Science.gov (United States)

    Jankovic, Slobodan M; Ignjatovic Ristic, Dragana

    2015-03-01

    Therapeutic window of anticonvulsants is not a wide one, with phenytoin being one extreme, which can be classified as a narrow therapeutic index drug, since its ratio between the least toxic and the least effective concentration is less than twofold. In order to obtain marketing authorization, a generic anticonvulsant should demonstrate relative bioequivalence with its brand-name counterpart. However, although bioequivalent, generic anticonvulsants still do not have the same bioavailability as brand-name drugs, which may lead to larger fluctuations of steady-state plasma concentrations, and sometimes to loss of seizure control if a patient is switched from brand-name to generic or from generic to generic anticonvulsant. Generic anticonvulsants are effective, safe and affordable drugs for treatment of epilepsy, and patients could be successfully treated with them from the very beginning. It is switching from brand-name to generic anticonvulsant or from one generic anticonvulsant to another that should be avoided in clinical practice, since subtle differences in bioavailability may disturb optimal degree of seizure control to which the patient was previously successfully titrated.

  4. Teratogenicity and anticonvulsants: lessons from neurology to psychiatry.

    Science.gov (United States)

    Viguera, Adele Casals; Koukopoulos, Alexia; Muzina, David J; Baldessarini, Ross J

    2007-01-01

    Anticonvulsants are considered first-line treatments for epilepsy, and some also exert useful effects as mood stabilizers for the treatment of bipolar (manic-depressive) disorder. Much of the research on anticonvulsant use during pregnancy has been done by neurologists studying women with epilepsy. Anticonvulsant use during pregnancy is associated with increased risk of fetal malformations, but withdrawing medication is highly risky for most women with epilepsy or bipolar disorder. Thus, careful clinical monitoring and coordinated care among patient, partner, obstetrician, and psychiatrist are necessary to limit both teratogenetic and neuropsychiatric risks. Several pregnancy registries have appeared. They include the International Registry of Antiepileptic Drugs and Pregnancy (EURAP), the North American Antiepileptic Pregnancy Registry, the International Lamotrigine Pregnancy Registry, the United Kingdom Epilepsy and Pregnancy Register, and the Australian Pregnancy Registry. Data from these registries are helping medical professionals in assessing risks associated with anticonvulsant use during pregnancy and communicating those risks to patients.

  5. Mitochondrial Profiles and the Anticonvulsant Effect of the Ketogenic Diet

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    J Gordon Millichap

    2006-09-01

    Full Text Available A study of the anticonvulsant effect of the ketogenic diet (KD in adolescent rats, at Emory University and other centers, found that the hippocampus responds by inducing mitochondrial biogenesis, enhancing metabolic gene expression, and increasing energy reserves.

  6. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6......This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  7. [Lithium and anticonvulsants in bipolar depression].

    Science.gov (United States)

    Samalin, L; Nourry, A; Llorca, P-M

    2011-12-01

    For decades, lithium and anticonvulsants have been widely used in the treatment of bipolar disorder. Their efficacy in the treatment of mania is recognized. These drugs have been initially evaluated in old and methodologically heterogeneous studies. Their efficacy in bipolar depression has not always been confirmed in more recent and methodologically more reliable studies. Thus, lithium's efficacy as monotherapy was challenged by the study of Young (2008) that showed a lack of efficacy compared with placebo in the treatment of bipolar depression. In two recent meta-analyses, valproate has shown a modest efficacy in the treatment of bipolar depression. As for lithium, valproate appeared to have a larger antimanic effect for acute phase and prophylaxis of bipolar disorder. In contrast, lamotrigine is more effective on the depressive pole of bipolar disorder with better evidence for the prevention of depressive recurrences. The guidelines include these recent studies and recommend lamotrigine as a first-line treatment of bipolar depression and for maintenance treatment. Because of more discordant data concerning lithium and valproate, these two drugs are placed either as first or as second line treatment of bipolar depression. The different safety/efficacy ratios of mood stabilizers underlie the complementarity and the importance of combination between them, or with some second-generation antipsychotics, in the treatment of patients with bipolar disorder.

  8. ANTICONVULSANT ACTIVITY OF MORINGA OLEIFERA LEAF

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    Amrutia Jay N

    2011-07-01

    Full Text Available Moringa oleifera which is commonly known as drumstick tree has been used for its nutrition value and extensively used as a CNS depressant traditionally. Present work has been carried out to evaluate the anticonvulsant activity of methanolic extract of M. oleifera leaves against pentylenetetrazole (PTZ and maximal electroshock (MES induced convulsions at different dose level (200 mg/kg and 400 mg/kg i.p.. Diazepam and phenytoin (5mg/kg i.p. and 25mg/kg i.p., respectively were used as a reference standard. At both the doses it significantly (P < 0.0001 delayed the onset of clonic seizures in PTZ induced convulsions and significantly reduced (P < 0.0001 duration of hind limb extension in MES test. The phytochemical investigation of plant revealed the presence of alkaloids, flavonoids, tannins and saponins as major constituents. The data obtained indicates that methanolic extract of M. oleifera leaves may help to control grand mal and petit mal epilepsy.

  9. Anticonvulsant and antipunishment effects of toluene.

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    Wood, R W; Coleman, J B; Schuler, R; Cox, C

    1984-08-01

    Toluene can have striking acute behavioral effects and is subject to abuse by inhalation. To determine if its actions resemble those of drugs used in the treatment of anxiety ("anxiolytics"), two sets of experiments were undertaken. Inasmuch as prevention of pentylenetetrazol-induced convulsions is an identifying property of this class of agents, we first demonstrated that pretreatment with injections of toluene delayed the onset of convulsive signs and prevented the tonic extension phase of the convulsant activity in a dose-related manner. Injections of another alkyl benzene, m-xylene, were of comparable potency to toluene. Inhalation of toluene delayed the time to death after pentylenetetrazol injection in a manner related to the duration and concentration of exposure; at lower convulsant doses, inhalation of moderate concentrations (EC50, 1311 ppm) prevented death. Treatment with a benzodiazepine receptor antagonist (Ro 15-1788) failed to reduce the anticonvulsant activity of inhaled toluene. Anxiolytics also attenuate the reduction in response rate produced by punishment with electric shock. Toluene increased rates of responding suppressed by punishment when responding was maintained under a multiple fixed-interval fixed-interval punishment schedule of reinforcement. Distinct antipunishment effects were observed after 2 hr of exposure to 1780 and 3000 ppm of toluene; the rate-increasing effects of toluene were related to concentration and to time after the termination of exposure. Thus, toluene and m-xylene resemble in several respects clinically useful drugs such as the benzodiazepines.

  10. Anticonvulsant and antipunishment effects of toluene

    Energy Technology Data Exchange (ETDEWEB)

    Wood, R.W.; Coleman, J.B.; Schuler, R.; Cox, C.

    1984-01-01

    Toluene can have striking acute behavioral effects and is subject to abuse by inhalation. To determine if its actions resemble those of drugs used in the treatment of anxiety (anxiolytics), two sets of experiments were undertaken. Inasmuch as prevention of pentylenetetrazol-induced convulsions is an identifying property of this class of agents, the authors first demonstrated that pretreatment of mice with injections of toluene delayed the onset of convulsive signs and prevented the tonic extension phase of the convulsant activity in a dose-related manner. Injections of another alkyl benzene, m-xylene, were of comparable potency to toluene. Inhalation of toluene delayed the time of death after pentylenetetrazol injection in a manner related to the duration and concentration of exposure; at lower convulsant doses, inhalation of moderate concentrations (EC/sub 58/, 1300 ppm) prevented death. Treatment with a benzodiazepine receptor antagonist (Ro 15-1788) failed to reduce the anticonvulsant activity of inhaled toluene. Anxiolytics also attenuate the reduction in response rate produced by punishment with electric shock. Toluene increased rates of responding suppressed by punishment when responding was maintained under a multiple fixed-interval fixed-interval punishment schedule of reinforcement. Distinct antipunishment effects were observed in rats after 2 hr of exposure to 1780 and 3000 ppm of toluene; the rate-increasing effects of toluene were related to concentration and to time after the termination of exposure. Thus, toluene and m-xylene resemble in several respects clinically useful drugs such as the benzodiazepines. 51 references, 3 figures, 2 tables.

  11. Anticonvulsant Effectiveness and Hemodynamic Safety of Midazolam in Full-Term Infants Treated with Hypothermia

    NARCIS (Netherlands)

    van den Broek, MPH; Van Straaten, Henrica L M; Huitema, Alwin D R; Egberts, Toine; Toet, MC; De Vries, Linda S.; Rademaker, Karin; Groenendaal, Floris

    2015-01-01

    Background: Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients. Objectives: The objective was to evaluate the anticonvulsant effectiveness and h

  12. Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia

    NARCIS (Netherlands)

    Van Den Broek, Marcel P H; Van Straaten, Henrica L M; Huitema, Alwin D R; Egberts, Toine|info:eu-repo/dai/nl/162850050; Toet, Mona C.; De Vries, Linda S.; Rademaker, Karin; Groenendaal, Floris

    2015-01-01

    Background: Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients. Objectives: The objective was to evaluate the anticonvulsant effectiveness and h

  13. Anticonvulsant effects of Searsia dentata (Anacardiaceae) leaf extract in rats

    DEFF Research Database (Denmark)

    Pedersen, Mikael Egebjerg; Baldwin, Roger A; Niquet, Jerome;

    2010-01-01

    Searsia species are used in South Africa to treat epilepsy. Previous studies have demonstrated an in vitro N-methyl-D-aspartic acid (NMDA) receptor antagonistic effect of the ethanolic leaf extract. The aim of this study was to evaluate the potential anticonvulsant properties of the ethanolic...... extract of S. dentata in various animal models of epilepsy. The extract was submitted to a screening in anticonvulsant assays including NMDA-, kainic acid (KA)-, pentylenetetrazol (PTZ)- and bicuculline (BIC)-induced seizures in rats. The extract protected 47% of the PN 18 Wistar pups (postnatal day 18......% protection, p 8) in young adult and PN 18 rats, respectively. The ethanolic extract of S. dentata showed anticonvulsive properties in several models of epilepsy. These results are compatible with previous findings of NMDA receptor antagonism. Due to the complex composition of the extract...

  14. Pixe analysis of trace elements in tissues of rats treated with anticonvulsants

    Science.gov (United States)

    Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.

    1987-04-01

    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  15. The analgesic and anticonvulsant effects of piperine in mice.

    Science.gov (United States)

    Bukhari, I A; Pivac, N; Alhumayyd, M S; Mahesar, A L; Gilani, A H

    2013-12-01

    Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (Ppepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

  16. The efficacy of anticonvulsants on orofacial pain: a systematic review

    NARCIS (Netherlands)

    Martin, W.J.J.M.; Forouzanfar, T.

    2011-01-01

    Objective. Controversy exists about the effectiveness of anticonvulsants for the management of orofacial pain disorders. To ascertain appropriate therapies, a systematic review was conducted of existing randomized controlled trials. Study design. Trials were identified from PubMed, Cochrane, and Ovi

  17. Synthesis and anticonvulsant activity of certain chalcone based pyrazoline compounds

    Directory of Open Access Journals (Sweden)

    Sudhakara Rao Gerapati

    2015-09-01

    Full Text Available Convulsions are involuntary, violent, spasmodic and prolonged contractions of skeletal muscles. That means a patient may have epilepsy without convulsions and vice versa. Epilepsy is a common neurological abnormality affecting about 1% of the world population. The primary objectives of these synthesized compounds are to suppress seizures and provide neuroprotection by minimizing the effects from seizure attacks. Here some of the chalcones and chalcone based various pyrazolines were evaluated for anticonvulsant activity. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR & Mass spectroscopy. A preliminary evaluation of the prepared compounds has indicated that some of them exhibit moderate to significant anticonvulsant activity compared to a diazepam standard1-3.  All compounds were tested for their anticonvulsant activity using maximal electroshock induced convulsions (MES in mice at a dose level of 4 mg/kg.b.w. The compounds  Ph1, Ph2 , Py2 ,Py3 and Py4 have shown  to  good anticonvulsant activity when doses are administered as 25mg/ kg.b.w  , reduced the phases of seizures severity and  found to be active and also  increased survival rate. Remaining compounds are less efficacious.

  18. Anticonvulsive effects of nimodipine on penicillin-induced epileptiform activity.

    Science.gov (United States)

    Bağirici, Faruk; Bostanci, M Omer

    2006-01-01

    The common features of all types of epilepsy are synchronized and uncontrolled discharges of nerve cell assemblies. It is believed that calcium ions play an important role in the generation of epileptic activity. Excessive calcium influx into neurons is the first step toward a seizure. The aim of the present study is to investigate whether the calcium channel blocker nimodipine has anticonvulsive effects. The left cerebral cortex was exposed by craniotomy in anaesthetized rats. An epileptic focus was produced by injection of penicillin G potassium (500 units) into the somatomotor cortex. After the epileptiform activity reached maximum frequency and amplitude; nimodipine was injected into the same area. Application of nimodipine caused an inhibition in the electrocorticograms (ECoG). Solvent alone did not affect the epileptiform activity. The results of this study indicate that nimodipine may have anticonvulsant effects.

  19. Menthone aryl acid hydrazones: a new class of anticonvulsants.

    Science.gov (United States)

    Jain, Jainendra; Kumar, Y; Sinha, Reema; Kumar, Rajeev; Stables, James

    2011-01-01

    A series of ten compounds (Compounds J(1)-J(10)) of (±) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J(6), 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide was found to be the most active compound with MES ED(50) of 16.1 mg/kg and protective index (pI) of greater than 20, indicating that (±) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides.

  20. Coma blisters in 2 children on anticonvulsant medication.

    Science.gov (United States)

    Basu, Anna; Brown, Sara; Kirkham, Nigel; Ramesh, Venkateswaran; Leech, Suzy; Devlin, Anita

    2009-08-01

    Blister formation and eccrine sweat gland necrosis have been recognized to occur in states of impaired consciousness and were first reported following barbiturate intoxication. Their etiology is complex and cannot simply be explained by pressure effects. Now that barbiturates are less frequently used, clinicians are likely to be less aware of the phenomenon of coma blister formation; however, newer drugs have also been associated with the occurrence of coma blisters. We describe 2 new associations of coma blisters and anticonvulsants in children. In the first child, blisters recurred on multiple occasions along with obtundation and edema. Our aims are to alert clinicians to the occurrence of coma blisters in children sedated on anticonvulsant medications and to report the new finding of recurrent coma blisters.

  1. Anticonvulsant activity of aqueous extract of Leonotis leonurus.

    Science.gov (United States)

    Bienvenu, E; Amabeoku, G J; Eagles, P K; Scott, G; Springfield, E P

    2002-04-01

    Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p leonurus extract significantly (p leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.

  2. Bone Mineral Density in Patients Receiving Anticonvulsant Drugs

    Directory of Open Access Journals (Sweden)

    Kadir Yıldırım

    2002-12-01

    Full Text Available The study was carried out to determine possible effects of anticonvulsant drugs on bone mineral density. Twenty two patients with epilepsy who have been receiving anticonvulsant drugs and also 22 healthy controls were included in the study. The average age was 28.9 ± 8.9 years in the patients group and 30.5 ± 6.9 years in the control group. The average drug receiving time was 6.45 ± 4.2 years. At baseline ESR, hemogram, urine deoxypiridinoline (DPD, routine biochemical and hormonal values were determined in both groups. Lumbar spine and left femur bone mineral density (BMD values were determined with hologic 2000 DEXA. In the statistical analysis, urine DPD levels in the patient group were significantly higher than control group (p0.05. Lumbar spine and left femur BMD values were significantly decreased in patients group (respectively p<0.01, p<0.001. We determined that in the patients using anticonvulsant drugs there was an increase in bone resorption and this effect was more evident in cortical bone than trabecular bone.

  3. Anticonvulsant potentials of ethanolic extract of Eleusine indica

    Directory of Open Access Journals (Sweden)

    Ette Okon Ettebong

    2016-11-01

    Full Text Available Objective: To assess the anticonvulsant potentials of ethanolic extract of Eleusine indica. Methods: Albino Wistar mice were separated into five groups with six animals in each group and thereafter pretreated with distilled water, various doses of the extract (200–600 mg/kg and standard drug diazepam (0.5 mg/kg. Thirty minutes later, pentylenetetrazole (70 mg/kg, aminophylline (280 mg/kg and isoniazid (250 mg/kg were used to induce convulsions by intraperitoneal administration. These mice were then placed in plexiglas cages and monitored for the occurrence of seizures over a thirty-minute time period. The latency of convulsions, duration of tonic convulsions and mortality protection were recorded. Data obtained were analyzed using GraphPad InStat 3.10. Results: The results showed that the extract exhibited a dose-dependent increase in the latency of clonic convulsions and decrease in duration of tonic convulsions as compared to the control and these effects were statistically significant (P < 0.001. The extract also provided protection against the mortality which was similar to that produced by the standard drug diazepam. Conclusions: The significant increase in the latency of clonic convulsions and decrease in duration of tonic convulsions caused by the extract show anticonvulsant activity and corroborate with the claims of the traditional use of the plant as an anticonvulsant remedy.

  4. Comparative anticonvulsant potency and pharmacokinetics of (+)-and (-)-enantiomers of stiripentol.

    Science.gov (United States)

    Shen, D D; Levy, R H; Savitch, J L; Boddy, A V; Tombret, F; Lepage, F

    1992-06-01

    The anticonvulsant potency and pharmacokinetics of the enantiomers of stiripentol were compared using the intravenous pentylenetetrazol infusion seizure model in the rat. Enantioselectivity was observed with respect to both the anticonvulsant activity and elimination kinetics of this compound. (+)-Stiripentol was 2.4 times more potent than its antipode against pentylenetetrazol-induced clonic seizure (brain EC50 of 15.2 micrograms/ml versus 36.1 micrograms/ml). The (+)-enantiomer was eliminated more rapidly than the (-)-enantiomer, as reflected in a higher plasma clearance (1.64 l/h/kg versus 0.557 l/h/kg) and a shorter half-life (2.83 h versus 6.50 h). Parallel studies with the racemate of stiripentol indicated that the anticonvulsant potency of the racemate was between the potency of the two enantiomers, suggesting that the combined activity reflects the additive action of (+)- and (-)-stiripentol. However, a marked metabolic interaction between enantiomers was evident after racemate administration. These results point to the need for information on the differential pharmacokinetics of stiripentol enantiomers following racemic drug administration.

  5. Study of Convolvulus pluricaulis for antioxidant and anticonvulsant activity.

    Science.gov (United States)

    Verma, Sristi; Sinha, Reema; Kumar, Puspendra; Amin, Faizal; Jain, Jainendra; Tanwar, Shivani

    2012-03-01

    Convolvulus pluricaulis Choisy is a perennial wild herb commonly found on sandy & rocky areas under xerophytic conditions in northern India. It is a reputed drug of ayurveda and reported to posses antioxidant, brain tonic, nervine tonic, laxative and has been used in anxiety, neurosis, epilepsy, insomnia, burning sensation, oedema and urinary disorders. In the present study, methanolic extract of whole plant of Convolvulus pluricaulis Choisy was evaluated for antioxidant activity by using 1, 1-diphenyl-2-picryl- hydrazyl (DPPH) free radical scavenging model and anticonvulsant activity by using maximal electroshock seizure model. In antioxidant activity, ascorbic acid was used as standard agent while results of anticonvulsant studies were compared with phenytoin. Results of antioxidant activity have demonstrated significant free radical scavenging effect for methanolic extract of Convolvulus pluricaulis Choisy. IC50 value of methanolic extract was observed as 41.00μg/ml as compared to 2.03μg/ml of ascorbic acid. Methanolic extract of C. pluricaulis was evaluated for anticonvulsant activity at 250, 500 and 1000mg/kg. Experimental results have shown that at the dose of 500 and 1000mg/kg, C. pluricaulis didn't abolish the hind limb extension, but reduced the mean recovery time from convulsion.

  6. Anticonvulsant potentials of ethanolic extract ofEleusine indica

    Institute of Scientific and Technical Information of China (English)

    Ette Okon Ettebong; Edidiong Etukakpan; Augustine Bassey

    2016-01-01

    ABSTRACT Objective:To assess the anticonvulsant potentials of ethanolic extract ofEleusine indica. Methods:Albino Wistar mice were separated into five groups with six animals in each group and thereafter pretreated with distilled water, various doses of the extract (200–600 mg/kg) and standard drug diazepam (0.5 mg/kg). Thirty minutes later, pentylenetetrazole (70 mg/kg), aminophylline (280 mg/kg) and isoniazid (250 mg/kg) were used to induce convulsions by intraperitoneal administration. These mice were then placed in plexiglas cages and monitored for the occurrence of seizures over a thirty-minute time period. The latency of convulsions, duration of tonic convulsions and mortality protection were recorded. Data obtained were analyzed using GraphPad InStat 3.10. Results: The results showed that the extract exhibited a dose-dependent increase in the latency of clonic convulsions and decrease in duration of tonic convulsions as compared to the control and these effects were statistically significant (P < 0.001). The extract also provided protection against the mortality which was similar to that produced by the standard drug diazepam. Conclusions: The significant increase in the latency of clonic convulsions and decrease in duration of tonic convulsions caused by the extract show anticonvulsant activity and corroborate with the claims of the traditional use of the plant as an anticonvulsant remedy.

  7. Sudden unexpected death in epilepsy following resective epilepsy surgery in two patients withdrawn from anticonvulsants.

    Science.gov (United States)

    Mansouri, Alireza; Alhadid, Kenda; Valiante, Taufik A

    2015-09-01

    We report sudden unexpected death in epilepsy (SUDEP) following resective epilepsy surgery in two patients who had been documented as seizure free. One patient had been weaned off of anticonvulsants and was leading a normal life. The other patient had discontinued only one anticonvulsant but had recently started working night shifts. Following resective epilepsy surgery, one of the major objectives among patients, caregivers, and the healthcare team is to safely wean patients off anticonvulsant medications. The main concern regarding anticonvulsant withdrawal is seizure recurrence. While SUDEP following surgical resection has been reported, to our knowledge, there have been no confirmed cases in patients who have been seizure free. Considering the patients reported here, and given that there are no concrete guidelines for the safe withdrawal of anticonvulsants following epilepsy surgery, the discontinuation of anticonvulsants should be considered carefully and must be accompanied by close monitoring and counseling of patients regarding activities that lower seizure threshold, even after successful epilepsy surgery.

  8. 3,4-DHQLO and Triazole and Its Related Analogues with Anticonvulsant Effects.

    Science.gov (United States)

    Guan, Li-Ping; Quan, Zhe-Shan

    2016-01-01

    The derivatives of quinolinone and triazole exhibit antitumor, antiplatelet, antidepressant, and anticonvulsant properties in diverse experimental systems. In the past decades, we have developed increasingly potent anticonvulsant agents by the structural modification of compounds derived from 3,4-DHQLO, triazole, and their analogs. Herein, we report the design and synthesis of a new series of 3,4-DHQLO and triazole and their derivatives; their anticonvulsant activity was evaluated. Moreover, we also reviewed the anticonvulsant activity of 3,4-DHQLO and triazole and their derivatives and new approaches.

  9. New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol.

    Science.gov (United States)

    Bebin, M; Bleck, T P

    1994-08-01

    In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.

  10. Anticonvulsant use in elderly patients in long-term care units.

    LENUS (Irish Health Repository)

    Timmons, S

    2012-02-03

    BACKGROUND: Elderly patients in long-term care units are frailer than their community-dwelling peers and may be more at risk from toxic side-effects of anticonvulsant medication at standard doses. AIM: To examine the prescribing of anticonvulsants to patients in elderly care units. METHODS: Drug prescription sheets and case notes were reviewed. Serum anticonvulsant concentration, renal and liver profiles and albumin level were measured. RESULTS: Anticonvulsants were prescribed to twice as many male as female patients (32 vs 14%; p<0.03) and to 33% of those younger than 80 years of age versus 10% of those aged 80 years or older (p<0.0002). No patient had significant hypoalbuminaemia and routine measurement of serum anticonvulsant concentration did not indicate an alteration of dosage. CONCLUSIONS: Anticonvulsants appear to be well tolerated in these patients. The younger age of those receiving anticonvulsants is inadequately explained by the characteristics of the patient cohort and may reflect a shift towards a younger age in patients requiring anticonvulsants due to increased mortality in this group.

  11. Anticonvulsant pharmacotherapy for generalized and localized vulvodynia : a critical review of the literature

    NARCIS (Netherlands)

    Spoelstra, Symen K.; Borg, Charmaine; Schultz, Willibrord C. M. Weijmar

    2013-01-01

    Anticonvulsant therapy has occasionally been recommended to treat vulvodynia. However, convincing evidence to support this therapeutic option is lacking. The goal of this study was to critically review studies published on the effectiveness of anticonvulsants for the treatment of vulvodynia. Evaluat

  12. Effect of tianeptine on seizure threshold and anticonvulsant activity of valproate, phenobarbitone and phenytoin in mice

    Directory of Open Access Journals (Sweden)

    Ashok K. Sharma

    2016-06-01

    Conclusions: Tianeptine exhibits anticonvulsant action which is synergistic with anticonvulsant effects of valproate, phenobarbitone and phenytoin suggesting that tianeptine may be a safe option in patients of epilepsy concurrently suffering from depression. [Int J Basic Clin Pharmacol 2016; 5(3.000: 850-854

  13. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD...

  14. [Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

    Science.gov (United States)

    Alikina, N A; Tregubov, A L; Kotegov, V P

    2010-08-01

    The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

  15. Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity

    Institute of Scientific and Technical Information of China (English)

    AGGARWAL Navneet; MISHRA Pradeep

    2005-01-01

    Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

  16. Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles

    Directory of Open Access Journals (Sweden)

    Bhawna Sharma

    2013-01-01

    Full Text Available The chemistry of heterocyclic compounds has been an interesting field of study for a long time. Heterocyclic nucleus 1,3,4-thiadiazole constitutes an important class of compounds for new drug development. The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an active area of intensive investigation in medicinal chemistry. During the recent years, there has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities, namely, antimicrobial activity, anticonvulsant, antifungal antidiabetic, anti-inflammatory, antioxidant, and antituberculosis activities, and so forth. The resistance towards available drugs is rapidly becoming a major worldwide problem. The need to design new compounds to deal with this resistance has become one of the most important areas of research today. Thiadiazole is a versatile moiety that exhibits a wide variety of biological activities. Thiadiazole moiety acts as “hydrogen binding domain” and “two-electron donor system.” It also acts as a constrained pharmacophore. On the basis of the reported literature, we study here thiadiazole compounds and their synthetic methods chemistry and anticonvulsant activity.

  17. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists.

    Science.gov (United States)

    Sadek, Bassem; Saad, Ali; Schwed, Johannes Stephan; Weizel, Lilia; Walter, Miriam; Stark, Holger

    2016-01-01

    Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%-80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide (1). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide (2) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S-enantiomer (1), the results show that animals pretreated intraperitoneally (ip) with the R-enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R)-enantiomer (3), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its (S)-enantiomer (4) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R)-enantiomer (3) in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and

  18. The role of topiramate and other anticonvulsants in the treatment of alcohol dependence: a clinical review.

    Science.gov (United States)

    De Sousa, Avinash

    2010-03-01

    Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions.

  19. Evaluation of sedative and anticonvulsant activities of Unmadnashak Ghrita.

    Science.gov (United States)

    Achliya, Girish S; Wadodkar, Sudhir G; Dorle, Avinash K

    2004-09-01

    'Unmadnashak Ghrita' (UG) is a ayurvedic formulation containing Ferula narthex (6 g), Gardenia gummifera (6 g), Ellataria cardamom (6 g), Bacopa monneri (6 g), and cow's ghee (clarified butter fat) (76 g). In the present study, neuropharmacological activities of UG were evaluated for its gross behavioural effect, pentobarbitone sleeping time, spontaneous locomotor activity, antagonism to amphetamine induced hyperlocomotor activity, analgesic activity by tail flick test, rota-rod performance (motor coordination test), maximal electroshock (MES) induced seizures, and pentylenetetrazol (PTZ) induced convulsions in mice. The formulation showed CNS-depressant activity in gross behavioural test, potentiated pentobarbitone sleeping time and there was significant decrease in spontaneous locomotor count in mice. The formulation also antagonized the behavioral effects of CNS-stimulant drug amphetamine, and showed analgesic effect in mice. UG failed to affect the motor coordination test. The formulation also protected mice from MES and PTZ induced convulsions. These results suggest that UG has CNS-depressant and anticonvulsant activity in mice.

  20. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    Full Text Available Bassem Sadek,1 Ali Saad,1 Johannes Stephan Schwed,2,3 Lilia Weizel,2 Miriam Walter,2 Holger Stark2,3 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Biocenter, Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: Phenytoin (PHT, valproic acid, and modern antiepileptic drugs (AEDs, eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropanamide (1. In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropaneamide (2 and analogs thereof, in maximum electroshock (MES-, pentylenetetrazole (PTZ-, and strychnine (STR-induced convulsion models in rats having PHT and valproic acid (VPA as reference AEDs. Unlike the S-enantiomer (1, the results show that animals pretreated intraperitoneally (ip with the R-enantiomer 2 (10 mg/kg were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R-enantiomer (3

  1. Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists.

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    Sadek, Bassem; Kuder, Kamil; Subramanian, Dhanasekaran; Shafiullah, Mohamed; Stark, Holger; Lażewska, Dorota; Adem, Abdu; Kieć-Kononowicz, Katarzyna

    2014-06-01

    To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic drugs (AEDs), aromatic ether, and diether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in the maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in rats. The anticonvulsive effects of a systemic injection of 1-12 on MES-induced and PTZ-kindled seizures were evaluated against the reference AED phenytoin (PHT) and the structurally related H3R antagonist/inverse agonist pitolisant (PIT). Among the most promising ligands 2, 4, 5, and 11, there was a significant and dose-dependent reduction in the duration of tonic hind limb extension (THLE) in MES-induced seizure subsequent to administration of 4 and 5 [(5, 10, and 15 mg/kg, intraperitoneally (i.p.)]. The protective effects observed for the 1-(3-(3-(4-chlorophenyl)propoxy)propyl)-3-methylpiperidine derivative 11 at 10 mg/kg, i.p. were significantly greater than those of PIT, and were reversed by pretreatment with the central nervous system penetrant H1R antagonist pyrilamine (PYR) (10 mg/kg). Moreover, the protective action of the reference AED PHT, at a dose of 5 mg/kg (without considerable protection in the MES model), was significantly augmented when coadministered with derivative 11 (5 mg/kg, i.p.). Surprisingly, pretreatment with derivative 7 (10 mg/kg, i.p.), an ethylphenoxyhexyl-piperidine derivative without considerable protection in the MES model, potently altered PTZ-kindled seizure, significantly prolonged myoclonic latency time, and clearly shortened the total seizure time when compared with control, PHT, and PIT. These interesting results highlight the potential of H3R ligands as new AEDs or as adjuvants to available AED therapeutics.

  2. Evaluation of anticonvulsant and nootropic effect of ondansetron in mice.

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    Jain, S; Agarwal, N B; Mediratta, P K; Sharma, K K

    2012-09-01

    The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.

  3. Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity

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    Arnab Dhar

    2016-01-01

    Full Text Available Background: Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic and inhibitory (GABAergic neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. Aim: A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd. Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L. is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali. The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. Materials and Methods: In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES and Pentylenetetrazole (PTZ induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. Results: The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD and glutathione (GSH levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. Conclusion: These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.

  4. Serum Thyroid Hormone Levels in Epileptic Children Receiving Anticonvulsive Drugs

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    Abolfazl MAHYAR

    2011-12-01

    Full Text Available How to Cite this Article: Mahyar A, Ayazi P, Dalirani R, Hosseini SM, Daneshi Kohan MM. Serum Thyroid Hormone Levels in Epileptic Children Receiving AnticonvulsiveDrugs. Iranian Journal of Child Neurology 2011;5(4:21-24.ObjectiveThe aim of this study was to investigate serum thyroid hormone levels in epileptic children receiving anticonvulsive drugs.Materials & MethodsIn this case- control study, 30 epileptic children who were receiving anticonvulsive drugs (case group were compared with 30 healthy children (control group. This study was carried out in the Qazvin Children's Hospital (Qazvin, Iran from October to December 2007. Both groups were matched for age and sex. Thyroid hormone levels were measured using a radioimmunoassay and immunoradiometric assay. Data were analyzed using Chi-square and Student's t-tests.ResultsThe mean serum T3 and T4 levels in the case group were 2.36 ± 0.73 nmol/L and 95.96 ± 27.01 nmol/L, respectively, and the corresponding values in the control group were 1.88 ± 0.93 nmol/L and 147.46 ± 35.77 nmol/L, respectively. The mean serum thyroid-stimulating hormone (TSH levels in the case and control groups were 2.73±0.73 mIU/mL and 2.49 ± 2.17mIU/mL, respectively.ConclusionThis study revealed that long-term consumption of anticonvulsive drugs resulted in a decline in serum T4 levels and an increase in serum T3 levels, but had no effect on TSH levels. 1. Johnston M. Neurodegenerative disorders of childhood;Spingolipidoses. Nelson textbook of pediatrics, 17th edPhiladelphia: Saunders; 2004.P.2031-2.2. Sankar R, Koh S, Wu J, Menkes J. Paroxysmal disorders.In(eds: Menkes JH, Sarnat HB, Maria BL. ChildNeurology; 2006.P.7:877.3. Shiva S, Ashrafi M, Mostafavi F, Abasi F, RahbariA, Shabanian R. Effects of anticonvulsant drugs onthyroid function tests. Iranian Journal of pediatrics2003;13(02:101.4. Kimura M, Yoshino K, Suzuki N, Maeoka Y. Effect ofantiepileptic drugs on thyroid function. Psychiatry andclinical neurosciences

  5. Potential role of anticonvulsants in the treatment of obsessive-compulsive and related disorders.

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    Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

    2014-10-01

    We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders.

  6. Synthesis and biological evaluation of some novel quinoxaline derivatives as anticonvulsant agents.

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    Elhelby, Abdelghany Aly; Ayyad, Rezk Rezk; Zayed, Mohamed Fathalla

    2011-01-01

    In view of their expected anticonvulsant activity, some new derivatives of quinonxaline (V1-7) were designed and synthesized by condensation of different aromatic aldehydes with 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetohydrazide (IV). All synthesized compounds were isolated and confirmed by IR, 1H-NMR, MS, elemental analysis and then tested as anticonvulsant agents. Compound V3 and V1 showed the highest anticonvulsant effect with anticonvulsant potency relative to phenobarbital sodium of 0.8 and 0.75 whereas compound V5 exhibited the lowest relative potency of 0.09. The other compounds showed variable activity between these values as follows: V2 = 0.19, V4 = 0.41, V6 = 0.1 and V7 = 0.15. All compounds showed less activity than the reference compound phenobarbital. But the compounds provided a basis for further optimization.

  7. Anticonvulsant effect of Persea americana Mill (Lauraceae) (Avocado) leaf aqueous extract in mice.

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    Ojewole, John A O; Amabeoku, George J

    2006-08-01

    Various morphological parts of Persea americana Mill (Lauraceae) (avocado) are widely used in African traditional medicines for the treatment, management and/or control of a variety of human ailments, including childhood convulsions and epilepsy. This study examined the anticonvulsant effect of the plant's leaf aqueous extract (PAE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Like the reference anticonvulsant agents used, Persea americana leaf aqueous extract (PAE, 100-800 mg/kg i.p.) significantly (p Persea americana leaf aqueous extract possesses an anticonvulsant property, and thus lends pharmacological credence to the suggested ethnomedical uses of the plant in the management of childhood convulsions and epilepsy.

  8. Tramadol and several anticonvulsants synergize in attenuating nerve injury-induced allodynia.

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    Codd, Ellen E; Martinez, Rebecca P; Molino, Lory; Rogers, Kathryn E; Stone, Dennis J; Tallarida, Ronald J

    2008-02-01

    Neuropathic pain results from injury or dysfunction of the central or peripheral nervous system. The treatment of neuropathic pain is challenging, in part because of its multiple etiologies. The present study explores combinations of the analgesic tramadol and each of four anticonvulsants in the treatment of surgically induced (ligation of the L5 spinal nerve) allodynia in rats. Each of the five drugs studied exhibited a dose-dependent antiallodynic effect. When studied in combination, tramadol and each of two of the anticonvulsants (topiramate and RWJ-333369) interacted synergistically at all three ratios studied, whereas tramadol and each of the other two anticonvulsants (gabapentin and lamotrigine) exhibited a synergistic antiallodynic effect at only one of three ratios investigated. In addition, tramadol and topiramate were found to interact synergistically in a nociceptive pain model, the mouse hot-plate test. These studies suggest the benefit of using combinations of analgesics and anticonvulsants in the relief of neuropathic pain.

  9. Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model

    NARCIS (Netherlands)

    Vinogradova, L.V.; Rijn, C.M. van

    2008-01-01

    Purpose: To study anticonvulsive and antiepileptogenic effects of singe levetiracetam (LEV) administration in the model of audiogenic kindling. Methods: Rats of Krushinsky-Molodkina (KM) strain genetically susceptible to severe audiogenic seizures received one intraperitoneal injection of saline, l

  10. [The original nootropic and neuroprotective drug noopept potentiates the anticonvulsant activity of valproate in mice].

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    Kravchenko, E V; Ponteleeva, I V; Trofimov, S S; Lapa, V I; Ostrovskaia, R U; Voronina, T A

    2009-01-01

    The influence of the original dipeptide drug noopept, known to possess nootrope, neuroprotector, and anxiolytic properties, on the anticonvulsant activity of the antiepileptic drug valproate has been studied on the model of corazole-induced convulsions in mice. Neither a single administration of noopept (0.5 mg/kg, i.p.) nor its repeated introduction in 10 or 35 days enhanced the convulsant effect of corazole, which is evidence that noopept alone does not possess anticonvulsant properties. Prolonged (five weeks) preliminary administration of noopept enhanced the anticonvulsant activity of valproate. This result justifies the joint chronic administration of noopept in combination with valproate in order to potentiate the anticonvulsant effect of the latter drug. In addition, the administration of noopept favorably influences the cognitive functions and suppresses the development of neurodegenerative processes.

  11. Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro

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    Karande Sunil

    2006-02-01

    Full Text Available Anticonvulsant hypersensitivity syndrome (AHS developing to lamotrigine, a non-aromatic anticonvulsant, has rarely been reported. We present a two-year-old boy with refractory epilepsy on valproic acid and lamotrigine therapy who developed fever and a maculopapular itchy rash. Blood investigations detected lymphocytosis and thrombocytopenia. With a presumptive diagnosis of AHS, lamotrigine was discontinued. The fever and rash resolved over the next three days and the child was discharged on valproic acid and clobazam. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which not only demonstrated increased cell death following exposure to lamotrigine, but also to the three first-line aromatic anticonvulsants: phenytoin, phenobarbital and carbamazepine. The potential of first-line aromatic anticonvulsants to cause AHS should be remembered in a patient who has developed AHS on exposure to lamotrigine. Timely recognition of this rare but potentially fatal drug reaction is important.

  12. The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice.

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    Pourgholami, M H; Majzoob, S; Javadi, M; Kamalinejad, M; Fanaee, G H; Sayyah, M

    1999-08-01

    This study investigates anticonvulsant effects of an essential oil of the fruits of Pimpinella anisum (Umbelliferae), a folkloric remedy in the Iranian traditional medicine, against seizures induced by pentylenetetrazole (PTZ) or maximal electroshock (MES) in male mice. The essential oil suppressed tonic convulsions induced by PTZ or MES. It also elevated the threshold of PTZ-induced clonic convulsions in mice. The essential oil produced motor impairment. However, this effect was not observed at the doses and time courses needed for anticonvulsant activity.

  13. Evaluation of anticonvulsant drugs during pregnancy in a population-based Hungarian study.

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    Czeizel, A E; Bod, M; Halász, P

    1992-01-01

    The Hungarian Case-Control Surveillance of Congenital Anomalies, from 1980-1987, involved 10,698 malformed cases and 21,546 non-malformed controls. Ninety-five pregnant women were treated by 144 anticonvulsants excluding diazepam and barbiturates. The rate of anticonvulsant use was 2.9 times higher in pregnant women having malformed offspring than in control mothers and this difference was greater in polytherapy than in monotherapy.

  14. A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

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    Reinares, María; Rosa, Adriane R; Franco, Carolina; Goikolea, José Manuel; Fountoulakis, Kostas; Siamouli, Melina; Gonda, Xenia; Frangou, Sophia; Vieta, Eduard

    2013-03-01

    Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

  15. Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

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    G.M.L. Reis

    2003-09-01

    Full Text Available It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11 and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11 models of epilepsy. Naloxone (5 mg/kg, sc significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test, suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc was demonstrable. The acute (120 mg/kg, ip and chronic (25 mg/kg, ip, twice a day/4 days administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures.

  16. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

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    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  17. Design and synthesis of novel stiripentol analogues as potential anticonvulsants.

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    Aboul-Enein, Mohamed N; El-Azzouny, Aida A; Attia, Mohamed I; Maklad, Yousreya A; Amin, Kamilia M; Abdel-Rehim, Mohamed; El-Behairy, Mohammed F

    2012-01-01

    A series of stiripentol (STP) analogues namely, 2-[(1E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ylidene]-N-(aryl/H)hydrazinecarboxamides 7a-h, (±)-(5RS)-N-(aryl/H)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazole-1-carboxamides (±)-8a-h, and (±)-[(5RS)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazol-1-yl](aryl)methanones (±)-13a-f was synthesized by adopting appropriate synthetic routes and was pharmacologically evaluated in the preliminary anticonvulsant screens. The selected bioactive new chemical entities were subjected to ED(50) determination and neurotoxicity evaluation. The most active congeners are 7h in MES screen and (±)-13b in scPTZ screen which displayed ED(50) values of 87 and 110 mg/kg, respectively, as compared to that of STP (ED(50) = 277.7 and 115 mg/kg in MES and scPTZ, respectively).

  18. Evaluation of anticonvulsants for possible use in neuropathic pain.

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    Waszkielewicz, A M; Gunia, A; Słoczyńska, K; Marona, H

    2011-01-01

    Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development. Therefore, it is already a phenomenon that researchers turn their projects toward a larger market, related with possible similar mechanism. Anticonvulsant mechanism of action is in the first place among primary indications for drugs revealing potential analgesic activity. Therefore, many drug candidates for epilepsy, still in preclinical stage, are being evaluated for activity in neuropathic pain. This review is focusing on antiepileptic drugs, which are evaluated for their analgesic activity in major tests related with neuropathic pain. Relation between structure, mechanism of action and result in tests such as the Chung model (spinal nerve ligation SNL), the Bennett model (chronic constriction injury of sciatic nerve CCI) and other tests are considered. The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with listed animal models has been discussed.

  19. Causes of CNS inflammation and potential targets for anticonvulsants.

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    Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

    2013-08-01

    Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

  20. Combination anticonvulsant treatment of soman-induced seizures.

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    Koplovitz, I; Schulz, S; Shutz, M; Railer, R; Macalalag, R; Schons, M; McDonough, J

    2001-12-01

    These studies investigated the effectiveness of combination treatment with a benzodiazepine and an anticholinergic drug against soman-induced seizures. The anticholinergic drugs considered were biperiden, scopolamine, trihexaphenidyl, and procyclidine; the benzodiazepines were diazepam and midazolam. Male guinea pigs were implanted surgically with cortical screw electrodes. Electrocorticograms were displayed continually and recorded on a computerized electroencephalographic system. Pyridostigmine (0.026 mg x kg(-1), i.m.) was injected as a pretreatment to inhibit red blood cell acetylcholinesterase by 30-40%. Thirty minutes after pyridostigmine, 2 x LD50 (56 microg x kg(-1)) of soman was injected s.c., followed 1 min later by i.m. treatment with atropine (2 mg x kg(-1)) + 2-PAM (25 mg x kg(-1)). Electrographic seizures occurred in all animals. Anticonvulsant treatment combinations were administered i.m. at 5 or 40 min after seizure onset. Treatment consisted of diazepam or midazolam plus one of the above-mentioned anticholinergic drugs. All doses of the treatment compounds exhibited little or no antiseizure efficacy when given individually. The combination of a benzodiazepine and an anticholinergic drug was effective in terminating soman-induced seizure, whether given 5 or 40 min after seizure onset. The results suggest a strong synergistic effect of combining benzodiazepines with centrally active anticholinergic drugs and support the concept of using an adjunct to supplement diazepam for the treatment of nerve-agent-induced seizures.

  1. Neuropeptides as targets for the development of anticonvulsant drugs.

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    Clynen, Elke; Swijsen, Ann; Raijmakers, Marjolein; Hoogland, Govert; Rigo, Jean-Michel

    2014-10-01

    Epilepsy is a common neurological disorder characterized by recurrent seizures. These seizures are due to abnormal excessive and synchronous neuronal activity in the brain caused by a disruption of the delicate balance between excitation and inhibition. Neuropeptides can contribute to such misbalance by modulating the effect of classical excitatory and inhibitory neurotransmitters. In this review, we discuss 21 different neuropeptides that have been linked to seizure disorders. These neuropeptides show an aberrant expression and/or release in animal seizure models and/or epilepsy patients. Many of these endogenous peptides, like adrenocorticotropic hormone, angiotensin, cholecystokinin, cortistatin, dynorphin, galanin, ghrelin, neuropeptide Y, neurotensin, somatostatin, and thyrotropin-releasing hormone, are able to suppress seizures in the brain. Other neuropeptides, such as arginine-vasopressine peptide, corticotropin-releasing hormone, enkephalin, β-endorphin, pituitary adenylate cyclase-activating polypeptide, and tachykinins have proconvulsive properties. For oxytocin and melanin-concentrating hormone both pro- and anticonvulsive effects have been reported, and this seems to be dose or time dependent. All these neuropeptides and their receptors are interesting targets for the development of new antiepileptic drugs. Other neuropeptides such as nesfatin-1 and vasoactive intestinal peptide have been less studied in this field; however, as nesfatin-1 levels change over the course of epilepsy, this can be considered as an interesting marker to diagnose patients who have suffered a recent epileptic seizure.

  2. Tolerance to anticonvulsant effects of diazepam, clonazepam, and clobazam in amygdala-kindled rats.

    Science.gov (United States)

    Rosenberg, H C; Tietz, E I; Chiu, T H

    1989-01-01

    Benzodiazepines are effective anticonvulsants, but long-term clinical usefulness is limited by development of tolerance. Tolerance to the actions of three prototype anticonvulsant benzodiazepines (BZDs)--diazepam (DZP), clonazepam (CZP), and clobazam (CLB)--was studied in amygdala-kindled rats. Fully kindled rats were dosed three times daily for 2 or 4 weeks. Amygdala stimulation was given 30 min after drug administration on days 1, 2, 3, 5, and 7 of chronic treatment and then three times weekly. During treatment, tolerance was observed as a loss of drug effect to suppress behavioral and EEG manifestations of seizure activity. Seizure activity remained stable in rats treated with vehicle. Tolerance to the anticonvulsant effects developed most rapidly during CLB treatment and most slowly during CZP treatment. Tolerance to the motor impairment caused by the drugs developed more rapidly. Assay of the amount of drug in brain extracts, using a BZD receptor assay, showed that tolerance was functional, not metabolic. Doubling the dose did not readily restore full anticonvulsant activity. The response to amygdala stimulation 24 h after treatment was stopped showed no residual BZD effect, but there was a rebound in duration of some seizure measures in rats that had been treated with CLB or DZP. Retesting 48 h after treatment was stopped showed that rats were still tolerant. The amygdala-kindled rat is a reliable and sensitive model for studying long-term actions of anticonvulsant BZDs.

  3. Repeated anticonvulsant testing: contingent tolerance to diazepam and clobazam in kindled rats.

    Science.gov (United States)

    Tietz, E I

    1992-04-01

    The acute anticonvulsant efficacy of diazepam (1.5 mg/kg, i.p.) was evaluated by repeated test injection in kindled rats subcutaneously implanted with diazepam-filled or empty silastic tubes for 3 weeks. Tolerance developed to acute test injections in both diazepam- and sham-implanted rats. Tolerance developed to a lesser extent in another group of diazepam-implanted rats which did not receive acute intermittent anticonvulsant tests. The hypothesis that contingent tolerance had developed to the anticonvulsant actions of benzodiazepines (diazepam, 1.5 mg/kg, i.p. and clobazam, 10 mg/kg, i.p.) in kindled rats given acute intermittent injections was investigated using a 'before-after' design. Significant contingent tolerance developed in rats which received intermittent benzodiazepine treatment before, but not after, amygdala stimulation. Tolerance developed to different extents depending on the seizure measure evaluated (forelimb clonus duration, amygdala afterdischarge duration, motor seizure latency and duration, and seizure stage). Contingent tolerance to both benzodiazepines developed at a similar rate. The findings suggest that contingent tolerance may contribute a sizeable component to the overall functional benzodiazepine tolerance measured in long-term anticonvulsant drug studies in kindled rats. Several questions regarding contingent tolerance phenomena are posed and the implications of these findings for studies using repeated anticonvulsant testing are discussed.

  4. Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

    Directory of Open Access Journals (Sweden)

    Franklin F. F. Nóbrega

    2014-01-01

    Full Text Available Terpinen-4-ol (4TRP is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p. at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v. at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p. inhibited pentylenetetrazol- (PTZ- induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v. protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP. The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

  5. Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats.

    Science.gov (United States)

    Amano, K; Takamatu, J; Kaneyama, H; Miyazaki, C; Deshimaru, M; Sumiyoshi, S; Ogata, A; Miyakawa, T

    1998-08-01

    We examined the anticonvulsant properties of dipotassium clorazepate (DC) against hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to kindling 1 week after the implantation of electrodes. After five stage 5 seizures were induced, the generalized convulsion triggering threshold (GST) was determined. Dipotassium clorazepate was administered intraperitoneally in rats that showed two stable stage 5 seizures induced at the GST current intensity. Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did not completely suppress after-discharges (AD) even at the highest dose, which was 5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an anticonvulsant. The results of the present study suggest that DC has a modest anticonvulsant potency. It is reasonable to assume that its anticonvulsant efficacy is primarily due to attenuation of AD propagation rather than the raising of the seizure triggering threshold at the kindling focus.

  6. Anticonvulsant activity of Dorema ammoniacum gum: evidence for the involvement of benzodiazepines and opioid receptors

    Science.gov (United States)

    Motevalian, Manijeh; Mehrzadi, Saeed; Ahadi, Samira; Shojaii, Asie

    2017-01-01

    This study investigated the anticonvulsant activity and possible mechanism of action of an aqueous solution of Dorema ammoniacum gum (DAG) which has been used traditionally in the treatment of convulsions. In this study, the anticonvulsant activity of DAG was examined using the pentylentetrazole (PTZ) model in mice. Thirty male albino mice were divided randomly and equally to 5 groups, and pretreated with normal saline, diazepam, or various doses of DAG (500, 700, and 1000 mg/kg, i.p.), prior to the injection of PTZ (60 mg/kg, i.p.). The latency and duration of seizures were recorded 30 min after PTZ injection. Pretreatments with naloxone and flumazenil in different groups were studied to further clarify the mechanisms of the anticonvulsant action. Phytochemical screening and thin layer chromatography (TLC) fingerprinting of ammoniacum gum was also determined. DAG showed significant anticonvulsant activity at all doses used. The gum delayed both the onset and the duration of seizures induced by PTZ. Treatment with flumazenil before DAG (700 mg/kg) inhibited the effect of gum on seizure duration and latency to some extent and administration of naloxone before DAG also significantly inhibited changes in latency and duration of seizure produced by DAG. The percentage inhibition was greater with naloxone than with flumazenil. This study showed that DAG had significant anticonvulsant activity in PTZ-induced seizures, and GABAergic and opioid systems may be involved. More studies are needed to further investigate its detailed mechanism. PMID:28255314

  7. Thyroid Function Test Imbalance in Epileptic Children Under Anticonvulsive Therapy

    Directory of Open Access Journals (Sweden)

    Mohammad TORKAMAN

    2012-03-01

    Full Text Available How to Cite this Article: Ravi Torkaman M, Amirsalari S, Saburi A. Thyroid Function Test Imbalance in Epileptic ChildrenUnder Anticonvulsive Therapy. Iranian Journal of Child Neurology 2012;6(1:43-44. Dear Editor,There have been many studies regarding the impact of antiepileptic drugs(AEDs on thyroid function. There are some challenging scopes which must beconsidered for conducting the study adressing the focused question. “Which oneof the thyroid hormones is related to the AEDs consumption?”. Some studiesdemonstrated that there may be alterations in all thyroid function tests (T3, T4 andTSH after antiepileptic therapy in children (1. Some studies concluded that longtermprescription of anticonvulsive medications resulted in a decline in serum T4levels, although it had no effect on serum TSH levels. However, changes in serumT3 level was challenging and it must be investigated further (2.There were some confounding factors which may interfere with the conclusion.One of them is the type of the study. There are various study plans for this purposesuch as cross-sectional, case-control, experimental, self-controlled cohort anddouble-blind randomized clinical trial studies. It seems that the proper protocol ofstudy for this propose is a double-blind randomized clinical trial study. By usingother designs, the authors cannot interpret the effect of AEDs on thyroid function;however, they can discuss the prevalence of thyroid hormone imbalance and thecoordination among T3, T4 and TSH.Moreover, one of the confounding factors is the thyroid binding globulin (TBGeffect. It has appeared that some of the AEDs may change the amount of TBGand in this way may affect the amount of thyroid hormones (3. Clonazepamand valproic acid do not have any enzyme inducing effects, but phenobarbital,carbamazepine, phenytoin and primidone may induce the hepatic enzyme (4-6. Therefore, it seems necessary to analyze each group of patients based on thetype of drug which is

  8. The importance of triazole scaffold in the development of anticonvulsant agents.

    Science.gov (United States)

    Ayati, Adile; Emami, Saeed; Foroumadi, Alireza

    2016-02-15

    Epilepsy is one of the most important neurological disorders with high prevalence worldwide. Many epileptic patients are not completely treated with available drugs and need multiple therapies. Also, many antiepileptic drugs have shown unwanted side effects and drug interactions. Therefore there are continuing interests to find new anticonvulsant drugs. Triazole ring has been found in the structure of many compounds with diverse biological effects. Due to the success of several triazole-containing drugs that entered the pharmaceutical market as CNS-active drugs, this class of heterocyclic compounds has great importance for discovery and development of new anticonvulsant drugs. In this article, we have tried to summarize the latest efforts which have been made in the design and development of triazole-derived anticonvulsant agents.

  9. 1,2,4-triazole derivatives as potential scaffold for anticonvulsant activity.

    Science.gov (United States)

    Kamboj, Vipan K; Verma, Prabhakar K; Dhanda, Anu; Ranjan, Sudhir

    2015-01-01

    The search for new anticonvulsant agent with more selectivity and lower toxicity continues to be an area of rigorous investigation in medicinal chemistry. Epilepsy is a chronic disorder of brain whose treatment consists of controlling seizures with antiepileptic drugs that very often related with side-effects which in rare circumstances can be potentially life-threatening. Triazolam and Alprazolam are established drugs used in epilepsy which have triazole moiety. The potency and broad spectrum of the pharmacological response of triazole moiety as anticonvulsant agent have attracted the attention of medicinal chemists to explore this framework for its potential. The literature shows that different substitution on triazole ring exhibit potent antiepileptic activity with no or lesser neurotoxicity. The present review is a sincere attempt to compile the reported potent triazole derivatives with significant anticonvulsant action.

  10. Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants.

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-08-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations has been controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. We propose that development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs.

  11. SYNTHESIS AND STUDY OF HALOGENATED BENZYLAMIDES OF SOME ISOCYCLIC AND HETEROCYCLIC ACIDS AS POTENTIAL ANTICONVULSANTS.

    Science.gov (United States)

    Strupińska, Marzanna; Rostafińska-Suchar, Grażyna; Pirianowicz-Chaber, Elżbieta; Grabczuk, Mateusz; Józwenko, Magdalena; Kowalczyk, Hubert; Szuba, Joanna; Wójcicka, Monika; Chen, Tracy; Mazurek, Aleksander P

    2015-01-01

    A series of potential anticonvulsants have been synthesized. There are eight fluorobenzylamides and three chlorobenzylamides of isocyclic or heterocyclic acids. Two not halogenated benzylamides were also synthesized to compare the effect of halogenation. The aim of the research performed was to evaluate whether halogenation of the mother structure is able to improve its anticonvulsant activity. The compounds were tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Compound 1 showed MES ED50 = 80.32 mg/kg, PI = 3.16. Compound 7 showed CKM ED50 = 56.72 mg/kg. Compound 8 showed MES ED50 = 34.23 mg/kg and scPTZ ED50 > 300 mg/kg, PI = 8.53.Compound 13 showed 6Hz ED50 = 78.96, PI = 3.37. The results indicate that fluorination does not improve activity, whereas chlorination in our experiment even reduces it.

  12. Evaluation of clorazepate (Tranxene) as an anticonvulsant--a pilot study.

    Science.gov (United States)

    Troupin, A S; Friel, P; Wilensky, A J; Morretti-Ojemann, L; Levy, R H; Feigl, P

    1979-04-01

    Desmethyldiazepam--providing the long-term anticonvulsant effect when diazepam is given orally--is conveniently administered as clorazepate (Tranxene). In this study, clorazepate was compared to phenobarbital as a secondary anticonvulsant in eight ambulatory, adult outpatients. Stable doses of phenytoin were maintained throughout. Drowsiness was present in all on phenobarbital, but there were no clorazepate-related side effects. Seizure control did not differ for each treatment. Addition of common side effects of phenytoin and phenobarbital limited the attained serum levels of each when used together. Clorazepate doses in the 0.56-mg-per-kilogram range gave desmethyldiazepam levels in the 1.0-microgram-per-milliliter range. Induction of metabolism was suggested by falling desmethyldiazepam levels despite increasing doses. Clorazepate is an effective, nontoxic secondary anticonvulsant.

  13. Search for anticonvulsant and analgesic active derivatives of dihydrofuran-2(3H)-one.

    Science.gov (United States)

    Więckowski, Krzysztof; Sałat, Kinga; Bytnar, Justyna; Bajda, Marek; Filipek, Barbara; Stables, James P; Malawska, Barbara

    2012-11-01

    A series of derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone, GBL) was synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In the anticonvulsant screening 10 lactones were effective in the maximal electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip, mice). Statistical analysis showed correlation between the anticonvulsant activity and relative lipophilicity parameters determined by experimental and computational methods (R(M0), ClogP and MlogP). Preliminary antinociceptive evaluation of selected derivatives revealed strong analgesic activity. The majority of the tested compounds showed high efficacy in animal models of acute pain (hot plate and writhing tests) and strong local anesthetic activity (modified tail immersion test). The obtained ED(50) values were comparable with such analgesics as acetylsalicylic acid and morphine.

  14. Tolerance to anticonvulsant effects of some benzodiazepines in genetically epilepsy prone rats.

    Science.gov (United States)

    De Sarro, G; Di Paola, E D; Aguglia, U; de Sarro, A

    1996-09-01

    The development of tolerance to the anticonvulsant effects of clonazepam, clobazam, and diazepam were studied in genetically epilepsy-prone rats following intraperitoneal (IP) or oral administration. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz). All compounds showed 60 min after IP injection antiseizure activity with ED50 against clonus of 0.24 mumol kg-1 for clonazepam, 0.72 mumol kg-1 for diazepam, and 3.9 mumol kg-1 for clobazam. After 120 min of oral administration the ED50 against clonus of 2.37 mumol kg-1 for clonazepam, 15.8 mumol kg-1 for diazepam, and 30 mumol kg-1 for clobazam. The dose chosen for the chronic treatment were 2.5 mumol kg-1 for clonazepam, 15 mumol kg-1 for diazepam, and 30 mumol kg-1 for clobazam. The animals were treated three times daily for 4 or 6 weeks. Auditory stimulation was administered 60 min after drug IP injection on various days. During treatment, tolerance was observed as a loss of drug anticonvulsant effects. No changes of occurrence of audiogenic seizures was observed in rats treated with vehicle. Tolerance to the anticonvulsant activity developed most rapidly during clobazam treatment, less rapidly following diazepam treatment, and most slowly during clonazepam treatment. Sixty minutes after IP injection on various days of chronic treatment the motor impairment induced by these benzodiazepines was also studied by means of a rotarod apparatus. The tolerance to the motor impairment developed more rapidly than the anticonvulsant effects. The response to auditory stimulation to benzodiazepines was stopped 24 and 48 h after chronic treatment with these compounds, showing no residual drug effects and that rats were still tolerant. The genetically epilepsy-prone rats is a reliable and sensitive model for studying long-term effects of anticonvulsant drugs.

  15. Association between consistent purchase of anticonvulsants or lithium and suicide risk: a longitudinal cohort study from Denmark, 1995-2001

    DEFF Research Database (Denmark)

    Smith, Eric G; Søndergård, Lars; Lopez, Ana Garcia;

    2009-01-01

    BACKGROUND: Prior studies suggest anticonvulsants purchasers may be at greater risk of suicide than lithium purchasers. METHODS: Longitudinal, retrospective cohort study of all individuals in Denmark purchasing anticonvulsants (valproic acid, carbamazepine, oxcarbazepine or lamotrigine) (n=9952......) or lithium (n=6693) from 1995-2001 who also purchased antipsychotics at least once (to select out nonpsychiatric anticonvulsant use). Poisson regression of suicides by medication purchased (anticonvulsants or lithium) was conducted, controlling for age, sex, and calendar year. Confounding by indication...... was addressed by restricting the comparison to individuals prescribed the same medication: individuals with minimal medication exposure (e.g., who purchased only a single prescription of anticonvulsants) were compared to those individuals with more consistent medication exposure (i.e., purchasing > or = 6...

  16. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Mosbacher, Johannes; Elg, Susanne;

    2002-01-01

    The actions of the anticonvulsant gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin] have been somewhat enigmatic until recently, when it was claimed to be a gamma-aminobutyric acid-B (GABA(B)) receptor agonist acting exclusively at a heterodimeric complex containing the GABA(B(1a...... in vitro assays. In light of these results, we find it highly questionable that gabapentin is a GABA(B) receptor agonist. Hence, the anticonvulsive effects of the compound have to arise from GABA(B) receptor-independent mechanisms. This also implies that the first GABA(B) receptor splice variant...

  17. [Psychotropic drugs - The special importance of anticonvulsants and neuroleptics in treatment of patients with chronic pain].

    Science.gov (United States)

    Brinkers, Michael; Petz, Tobias; Hoffmeyer, Dieter

    2011-01-01

    Therapy by psychotropic drugs is bound to limited indications, which are partially changing. By an extent literary research in pubmed and Cochrane especially corresponding articles of the past 10 years were proofed. So antidepressants were continually seldom given to nociceptor pain. While on the other side anticonvulsants are to be given in the case of neuropathic pain of defined quality, it will be looked for new applications for these drugs. Particularly hitherto existing difficult indications as fibromyalgia were investigated as possible indication for anticonvulsants. At least neuroleptics can be used for very difficult, resistant and bizarre pains such as cenesthesias.

  18. A new type of anticonvulsant, stiripentol. Pharmacological profile and neurochemical study.

    Science.gov (United States)

    Poisson, M; Huguet, F; Savattier, A; Bakri-Logeais, F; Narcisse, G

    1984-01-01

    4,4-Dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol (stiripentol), selected from a series of alpha-ethylene alcohols, demonstrated anticonvulsant activity in studies in the rat and rabbit in which convulsions were induced electrically and chemically using pentetrazol, bicuculline and strychnine. Neurochemical studies showed that stiripentol in vitro did not act as a GABA receptor agonist, instead it inhibited the synaptosomal uptake of 3H-labelled GABA. Stiripentol has been shown elsewhere to inhibit GABA transaminase. These findings suggest that the anticonvulsant activity of stiripentol involves two aspects of the GABAergic mechanism in which the metabolic transamination and synaptosomal uptake of this neurotransmitter are inhibited.

  19. ucb L059, a novel anti-convulsant drug: pharmacological profile in animals.

    Science.gov (United States)

    Gower, A J; Noyer, M; Verloes, R; Gobert, J; Wülfert, E

    1992-11-10

    The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions.

  20. Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening.

    Science.gov (United States)

    Siddiqui, Nadeem; Ahsan, Waquar

    2010-04-01

    Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED(50) values 23.9 mg/kg and 13.4 mg/kg respectively in MES screen and 178.6 mg/kg and 81.6 mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD(50)) and median lethal dose (LD(50)) much higher than the standard drugs.

  1. Volume-selective proton MR spectroscopy for in-vitro quantification of anticonvulsants

    Energy Technology Data Exchange (ETDEWEB)

    Braun, J.; Tolxdorff, T. [Inst. of Medical Informatics, Biometry and Epidemiology, University Hospital Benjamin Franklin, Berlin (Germany); Seyfert, S.; Marx, P. [Freie Univ. Berlin (Germany). Abt. fuer Neurologie; Bernarding, J. [Inst. of Medical Informatics, Biometry and Epidemiology, University Hospital Benjamin Franklin, Berlin (Germany); Freie Univ. Berlin (Germany). Klinik fuer Radiologie, Nuklearmedizin und Physikalische Therapie; Schilling, A. [Freie Univ. Berlin (Germany). Klinik fuer Radiologie, Nuklearmedizin und Physikalische Therapie

    2001-03-01

    Administration of anticonvulsant drugs is clinically monitored by checking seizure frequency and by determining the serum concentration of the drug. In a few reports, drug concentrations in brain parenchyma have been determined using ex vivo techniques. Little is known about the in vivo concentration in the brain parenchyma. Our goals were to characterise the NMR spectra of the anticonvulsants at therapeutic concentrations, to determine the minimum detectable concentrations, and to quantify the drugs noninvasively. Volume-selective 1H-MR spectroscopy (MRS) was performed under standard clinical conditions using a single-voxel STEAM (stimulated-echo acquisition mode) sequence at 1.5 T. Spectra of the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproate were acquired in vitro in hydrous solutions at increasing dilution. Phenytoin, phenobarbital and valproate were detectable below maximum therapeutic serum concentrations. Within therapeutic ranges, there was good agreement between concentrations determined by 1H-MRS and those by standard fluorescence polarisation immunoassay. Due to the absence of signals of brain metabolites, the aromatic protons of phenobarbital, phenytoin and carbamazepine, with resonance lines around 7.4 ppm, allow the drugs to be detected. Valproate, with two resonances around 1.2 ppm, should be differentiable from potential brain metabolites using nonlinear analysis of the brain spectrum. Volume-selective 1H-MRS is therefore expected to be able to monitor anticonvulsant therapy in vivo. (orig.)

  2. Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine : efficacy, safety and dosing

    NARCIS (Netherlands)

    van den Broek, Marcel P. H.; Rademaker, Carin M. A.; van Straaten, Henrica L. M.; Huitema, Alwin D. R.; Toet, Mona C.; de Vries, Linda S.; Egberts, Antoine C. G.; Groenendaal, Floris

    2013-01-01

    BACKGROUND: Lidocaine is an antiarrythmicum used as an anticonvulsant for neonatal seizures, also during therapeutic hypothermia following (perinatal) asphyxia. Hypothermia may affect the efficacy, safety and dosing of lidocaine in these patients. OBJECTIVE: To study the efficacy and safety of lidoc

  3. Anticonvulsant and related neuropharmacological effects of the whole plant extract of Synedrella nodiflora (L. Gaertn (Asteraceae

    Directory of Open Access Journals (Sweden)

    Patrick Amoateng

    2012-01-01

    Full Text Available Purpose: The plant Synedrella nodiflora (L Gaertn is traditionally used by some Ghanaian communities to treat epilepsy. To determine if this use has merit, we studied the anticonvulsant and other neuropharmacological effects of a hydro-ethanolic extract of the whole plant using murine models. Materials and Methods: The anticonvulsant effect of the extract (10-1000 mg/kg was tested on the pentylenetetrazole-, picrotoxin-, and pilocarpine-induced seizure models and PTZ-kindling in mice/rats. The effect of the extract was also tested on motor coordination using the rota-rod. Results: The results obtained revealed that the extract possesses anticonvulsant effects in all the experimental models of seizures tested as it significantly reduced the latencies to myoclonic jerks and seizures as well as seizure duration and the percentage severity. The extract was also found to cause motor incoordination at the higher dose of 1000 mg/kg. Conclusions: In summary, the hydro-ethanolic extract of the whole plant of S. nodiflora possesses anticonvulsant effects, possibly through an interaction with GABAergic transmission and antioxidant mechanisms and muscle relaxant effects. These findings thus provide scientific evidence in support of the traditional use of the plant in the management of epilepsy.

  4. Investigation of phytochemicals and anti-convulsant activity of the plant Coleus amboinicus (lour.

    Directory of Open Access Journals (Sweden)

    Prasenjit Bhattacharjee

    2013-01-01

    Full Text Available Objectives: The present study has been designed to evaluate the comparative anticonvulsant activity of different parts of Coleus amboinicus as it has been mentioned in the various literatures regarding the use of this plant in the treatment of epilepsy, but no specific scientific reports are available in this regard. Materials and Methods: The in vitro anticonvulsant activity of leaf, stem and roots of C. amboinicus has been evaluated by maximal electric shock-induced seizures (MES and Pentylenetetrazole (PTZ-induced seizures models in Swiss albino mice. The drug/extracts were administered through intra-peritoneal route (100 mg/ml, in both experimental models and the effect was compared with Phenytoin in MES and PTZ-induced convulsion. Results: All the three studied extracts have shown significant anticonvulsant activity in both the models. However, the alcoholic leaf extract has shown highest activity by abolishing the MES-induced convulsions after 60 minutes of drug administration. The duration of convulsions in PTZ model was also significantly reduced (P < 0.001 compared to the control group. Conclusion: The alcoholic leaf extract of the C. amboinicus has shown the significant anticonvulsant activity in both the studied models, followed by stem and root extracts. The presence of alkaloids, flavonoids, and saponins in these extracts may be responsible for this activity.

  5. Effect of low-frequency electrical stimulation parameters on its anticonvulsant action during rapid perforant path kindling in rat.

    Science.gov (United States)

    Shahpari, Marzieh; Mirnajafi-Zadeh, Javad; Firoozabadi, Seyed Mohammad P; Yadollahpour, Ali

    2012-03-01

    Low frequency stimulation (LFS) may be considered as a new potential therapy for drug-resistant epilepsy. However, the relation between LFS parameters and its anticonvulsant effects is not completely determined. In this study, the effect of some LFS parameters on its anticonvulsant action was investigated in rats. In all animals, stimulating and recording electrodes were implanted into the perforant path and dentate gyrus, respectively. In one group of animals, kindling stimulations were applied until rats achieved a fully kindled state. In other groups, different patterns of LFS were applied at the end of kindling stimulations during twenty consecutive days. In the first experiment the effect of LFS pulse numbers was investigated on its anticonvulsant action. Animals were divided randomly into three groups and 1, 4, and 8 packages of LFS (each pack contains 200 pulses, 0.1 ms pulse duration at 1 Hz) were applied five minutes after termination of kindling stimulations. Obtained results showed that 4 packages of LFS had the strongest anticonvulsant effects. Therefore, this pattern (4 packages) was used in the next experiment. In the second experiment, 4 packages of LFS were applied at intervals of 30 s and 30 min after termination of kindling stimulations. The strongest anticonvulsant effect was observed in the group received LFS at the interval of 30 s. Therefore, this pattern was selected for the third experiment. In the third experiment the effect of LFS at frequencies of 0.25 Hz and 5 Hz was investigated. The group of animals which received LFS at the frequency of 0.25 Hz showed somehow stronger anticonvulsant effect. The results indicate that different parameters of LFS have important role in induction of LFS anticonvulsant effects. Regarding this view, it seems that the slower LFS frequency and the shorter interval between LFS and kindling stimulations, the stronger anticonvulsant effect will be observed. But there is no direct relation between number of

  6. The efficacy and safety of newer anticonvulsants in patients with dementia.

    Science.gov (United States)

    Dolder, Christian R; Nealy, Kimberly L

    2012-08-01

    Anticonvulsants are a class of medications that have received considerable interest as possible treatments in patients with behavioural disturbances in dementia. The role of these medications for such a use remains controversial. The current paper reviews the published evidence surrounding the safety and efficacy (i.e. as a behavioural and cognitive treatment) of newer anticonvulsants in patients with dementia. A MEDLINE, International Pharmaceutical Abstracts, PsycINFO and clinicaltrials.gov search through to December 2011 was conducted for anticonvulsants that have received regulatory approval since 1996. Studies reporting behavioural or cognitive outcomes in patients with dementia were included. Nine trials involving only four medications met selection criteria and were included: levetiracetam (n = 4), oxcarbazepine (n = 1), topiramate (n = 2) and zonisamide (n = 2). Levetiracetam may have a role in the treatment of behavioural symptoms in dementia but study limitations substantially hinder the strength of such a recommendation. Oxcarbazepine and topiramate, based on limited data, do not appear to be effective treatments of behavioural symptoms in dementia. A lack of trials do not allow for conclusions to be made regarding zonisamide. From a cognitive standpoint, levetiracetam was the anticonvulsant most examined in patients with dementia, it appears to have less deleterious effects than some anticonvulsants. Limited data are available on the safety of these medications in elderly patients; however, studies completed thus far have demonstrated some adverse events that are more common or problematic with the use of these drugs in this patient population (i.e. somnolence, dizziness, hyponatraemia, weight loss).

  7. Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism

    Directory of Open Access Journals (Sweden)

    Mandeep Kaur

    2011-01-01

    Full Text Available “Ethnopharmacological” use of roots of Boerhaavia diffusa (B. diffusa in the treatment of epilepsy in Nigerian folk medicine and reports showing the presence of a calcium channel antagonistic compound “liriodendrin” in its roots, led us to undertake the present study. The study was designed to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. Air-dried roots of B. diffusa were extracted with methanol by cold maceration. The methanol soluble fraction of extract thus obtained was successively extracted to obtain liriodendrin-rich fraction and two side fractions, that is, chloroform fraction and phenolic compound fraction. Anti-convulsant activity of methanolic extract (1000, 1500 and 2000 mg kg-1, intraperitoneally (i.p. and its different fractions, that is, liriodendrin-rich fraction (10, 20 and 40 mg kg-1, i.p., chloroform fraction (20 mg kg-1, i.p. and phenolic compound fraction (1 mg kg-1, i.p. were studied in pentylenetetrazol (PTZ-induced seizures (75 mg kg-1, i.p.. The crude methanolic extract of B. diffusa and only its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions. The liriodendrin-rich fraction also showed significant protection against seizures induced by BAY k-8644. These findings reiterated the anti-convulsant activity of methanolic extract of B. diffusa roots. Furthermore, it can be concluded that the observed anti-convulsant activity was due to its calcium channel antagonistic action as this activity was retained only in the liodendrin-rich fraction, which has additionally been confirmed by significant anti-convulsant activity of liriodendrin-rich fraction in BAY k-8644-induced seizures.

  8. Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism.

    Science.gov (United States)

    Kaur, Mandeep; Goel, Rajesh Kumar

    2011-01-01

    "Ethnopharmacological" use of roots of Boerhaavia diffusa (B. diffusa) in the treatment of epilepsy in Nigerian folk medicine and reports showing the presence of a calcium channel antagonistic compound "liriodendrin" in its roots, led us to undertake the present study. The study was designed to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. Air-dried roots of B. diffusa were extracted with methanol by cold maceration. The methanol soluble fraction of extract thus obtained was successively extracted to obtain liriodendrin-rich fraction and two side fractions, that is, chloroform fraction and phenolic compound fraction. Anti-convulsant activity of methanolic extract (1000, 1500 and 2000 mg kg(-1), intraperitoneally (i.p.)) and its different fractions, that is, liriodendrin-rich fraction (10, 20 and 40 mg kg(-1), i.p., chloroform fraction (20 mg kg(-1), i.p.) and phenolic compound fraction (1 mg kg(-1), i.p.) were studied in pentylenetetrazol (PTZ)-induced seizures (75 mg kg(-1), i.p.). The crude methanolic extract of B. diffusa and only its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions. The liriodendrin-rich fraction also showed significant protection against seizures induced by BAY k-8644. These findings reiterated the anti-convulsant activity of methanolic extract of B. diffusa roots. Furthermore, it can be concluded that the observed anti-convulsant activity was due to its calcium channel antagonistic action as this activity was retained only in the liodendrin-rich fraction, which has additionally been confirmed by significant anti-convulsant activity of liriodendrin-rich fraction in BAY k-8644-induced seizures.

  9. Stiripentol is anticonvulsant by potentiating GABAergic transmission in a model of benzodiazepine-refractory status epilepticus.

    Science.gov (United States)

    Grosenbaugh, Denise K; Mott, David D

    2013-04-01

    Benzodiazepines (BZDs) are first-line therapy for treatment of status epilepticus (SE). However, BZD treatment is negatively affected by seizure duration due to decreases in BZD-sensitive GABA(A) receptors during prolonged SE. Stiripentol (STP) is an anticonvulsant that is used as add-on treatment for Dravet Syndrome. Recent studies have shown that STP is a positive allosteric modulator of the GABA(A) receptor. The subunit selectivity of STP at this receptor suggests that it would be anticonvulsant in both brief as well as prolonged SE. We tested this possibility by comparing the ability of STP and diazepam (DZP), a commonly used BZD, to terminate behavioral convulsions in a rodent model of pharmacoresistant SE. We found that STP was anticonvulsant in this model and remained effective during prolonged SE, unlike DZP which exhibited a 14 fold increase in its ED(50). Whole cell recording from hippocampal slices from these animals revealed that STP potentiated GABAergic IPSCs, as well as tonic GABAergic current by acting at a site on the GABA(A) receptor separate from the BDZ binding site. Potentiation of GABAergic currents by STP remained intact during prolonged SE, while potentiation by DZP was lost. Both IPSC potentiation and anticonvulsant activity of STP were greater in younger animals than in adults. These findings suggest that at doses that yield therapeutically relevant concentrations, STP is anticonvulsant by potentiating GABAergic inhibition and that the subunit selectivity profile of STP enables it to remain effective despite GABA(A) receptor subunit changes during prolonged SE.

  10. The anticonvulsant action of the galanin receptor agonist NAX-5055 involves modulation of both excitatory- and inhibitory neurotransmission

    DEFF Research Database (Denmark)

    Walls, Anne B; Flynn, Sean P; West, Peter J

    2016-01-01

    -based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti-convulsant......M NAX-5055 led to a reduction in the extracellular level of glutamate and an elevation of the extracellular level of GABA. Altogether these findings may at least partly explain the anti-convulsant effect of NAX-5055 observed in vivo....

  11. THE APPLICATION OF PASS-COMPUTER PROGRAMME AND MOLECULAR DOCKING FOR THE SEARCH OF NEW ANTICONVULSANTS

    Directory of Open Access Journals (Sweden)

    Perekhoda L.O.

    2014-12-01

    Full Text Available Introduction. Currently the priority goal of designing drugs is the integration of the methods of organic chemistry and pharmacology. The application of computer programmes which can predict interaction of Annals of potential drugs with molecules of biological targets makes possible to decrease the number of experiments on laboratory animals. Thereby the economic efficiency of production of new medicines increases. Models of the research the anticonvulsant activity (in particular, korazol, thiosemikarbazid, strychnine, etc. are the most rigid experimental models of pharmacological screening, which basically entails the pains of laboratory animals or their death. The application of computer programmes in the research of potential anticonvulsants has economic and social desirability and high level of importance for the pharmaceutical science and health care. The most perspective methods of research are the virtual screening, molecular docking. These methods allow to evaluate the affinity of a substance to a specific biological target, i.e. to identify an inhibitor of a particular enzyme or protein. Material and methods. We have carried out the construction of 50 groups substances (507 hypothetical structures. We have chosen the five-membered di(threeazaheterocycle as basic pharmacophores to form virtual structures because firstly their structure is similar to cyclic conformation of neurotransmitter and secondly according to the literature perspective anticonvulsants had already found among these derivatives. Computer prediction of pharmacological activity for all compounds of virtual database was performed using the PASS (Prediction of Activity Spectra for Substances computer programme. Results obtained by PASS-computer programme showed prospects of search the anticonvulsants among 10 groups of derivatives di(threeazaheterocycles (probable activity (Pa of substances of these groups are from 0.5 to 0.84. In order to determine the potential

  12. Evidence for use of mood stabilizers and anticonvulsants in the treatment of nonaffective disorders in children and adolescents.

    Science.gov (United States)

    Amaladoss, Alfred; Roberts, Nasreen; Amaladoss, Franklin

    2010-01-01

    Mood stabilizers and anticonvulsants have been frequently used to control behaviors in children and adolescent with nonaffective disorders. The purpose of this study was to review the literature to evaluate the evidence of these agents as treatment options in this subset of patients. We reviewed all the literature between 1949 and 2009 on the use of anticonvulsants and mood stabilizers in controlling severe behavior dysregulation and aggression in child and adolescent who do not meet the criteria for any mood disorder. The review revealed a total of 19 studies. Of the different mood stabilizers/anticonvulsants, both lithium and divalproex showed some promise in treating children and adolescents with nonmood disorders. Larger studies are nevertheless needed to support the ongoing use of these current anticonvulsants and mood stabilizers in children and adolescents with nonmood disorders. Also, further investigation to the potential use in the long term would need to be established, bearing in mind the balance of side effects and treatment benefit.

  13. The Anticonvulsant Effect of Transcutaneous Auricular Vagus Nerve Stimulation is Associated with Balancing the Autonomic Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Wei He

    2016-11-01

    Full Text Available Objective: The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.

  14. The anticonvulsant levetiracetam for the treatment of pain in polyneuropathy: A randomized, placebo-controlled, cross-over trial

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Otto, Marit; Bach, Flemming W;

    2011-01-01

    Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. OBJECTIVES: The aim.......293) or any of the other outcome measures (p=0.147-1.00). CONCLUSION: This study indicates that the anticonvulsant levetiracetam has no clinically relevant effect on painful polyneuropathy....

  15. Sedative, Anxiolytic and Anticonvulsant effects of different extracts from the leaves of Ipomoea Carnea in experimental Animals

    OpenAIRE

    Susanta Kumar Rout; Durga Madhab Kar

    2013-01-01

    The objective of this study is to investigate the sedative, anxiolytic and anticonvulsant activities of different leaf extracts of Ipomoea carnea. Materials and methods: The sedative effect of the different leaf extracts at dose level 100, 200 and 400 mg/kg was evaluated in mice and rats using phenobarbitone induced sleeping time and hole board models. Its anxiolytic effect was evaluated using the Evaluated Plus Maze (EPM) and the Y maze (YM) methods. The anticonvulsant activity was evaluated...

  16. Anticonvulsant and analgesic activities of crude extract and its fractions of the defensive secretion from the Mediterranean sponge, Spongia officinalis.

    OpenAIRE

    2012-01-01

    Abstract This study progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with anticonvulsant and analgesic activities. We investigated the efficacy of crude extract and its semi-purified fractions (F1-F3) of the defensive secretion from Spongia officinalis for their in vivo anticonvulsant activity using the pentylenetetrazole (PTZ) seizure model and analgesic activity using the writhing test in mice. Among the series the crude extract exhi...

  17. Design of benzothiazole-1,3,4-thiadiazole conjugates: synthesis and anticonvulsant evaluation.

    Science.gov (United States)

    Siddiqui, Nadeem; Ahuja, Priya; Malik, Sachin; Arya, Satish K

    2013-11-01

    Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7- to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity.

  18. What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

    Science.gov (United States)

    McCall, Catherine; McCall, W Vaughn

    2012-10-01

    Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

  19. Evaluation of anticonvulsant activity of hydroalcoholic extract of Mussaenda philippica on animals

    Institute of Scientific and Technical Information of China (English)

    Kar DM; Rout SK; Moharana L; Majumdar S

    2014-01-01

    Objective:To evaluate the anticonvulsant activity of hydroalcoholic extracts of leaves and sepals ofMussaenda philippica (M. Philippica) and its fractions(methanol, dioxin and aqueous) against pentylene tetrazole(PTZ), maximal electroshock(MES),Strychnine(STR),Picrotoxin induced convulsions at different dose levels.Methods:The anticonvulsant effect of extracts was studied by theMES,PTZ,STR andPicrotoxin-induced seizure.Results:The extract at100 and200 mg/kg, produced a significant(P<0.01) dose dependent increase in onset of convulsion compared to the control inMES,PTZ, strychnine and picrotoxin-induced seizures.Conclustions:The data obtained indicates thatHydroalcoholic extracts ofM. philippica leaves and sepals may help to control grandmal and petitmal epilepsy.

  20. Anticonvulsant and neuroprotective effects of oligosaccharides from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Higher Basidiomycetes).

    Science.gov (United States)

    Tello, Isaac; Campos-Pena, Victoria; Montiel, Elizur; Rodriguez, Veronica; Aguirre-Moreno, Alma; Leon-Rivera, Ismael; Del Rio-Portilla, Federico; Herrera-Ruiz, Maribel; Villeda-Hernandez, Juana

    2013-01-01

    An oligosaccharide fraction isolated from the mycelium of the Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (GLOS) was separated by size-exclusion chromatography. The chemical structure of GLOS consists of a disaccharide repeating unit [-4-β-1-Galf(1-6)-O-(β-Glcp)-1-]n (n=3,4). In addition, this study was undertaken to determine the possible anticonvulsant and neuroprotective effects of GLOS (10-80 mg/kg) on kainic acid (KA)-induced seizures. The behavioral alterations and histopathology of hippocampal neurons were studied. Our results show that GLOS inhibited convulsions in rats from KA-induced seizures, reduced the degeneration pattern in the CA3 region of rats, decreased astrocytic reactivity, and reduced the expression of IL-1β and TNF-α induced by KA. These results indicate a potential anticonvulsant and neuroprotective effects of GLOS.

  1. Computer-Aided Identification of Anticonvulsant Effect of Natural Nonnutritive Sweeteners Stevioside and Rebaudioside A.

    Science.gov (United States)

    Di Ianni, Mauricio E; Del Valle, María E; Enrique, Andrea V; Rosella, María A; Bruno, Fiorella; Bruno-Blanch, Luis E; Talevi, Alan

    2015-01-01

    Steviol glycosides are natural constituents of Stevia rebaudiana (Bert.) Bert. (Asteraceae) that have recently gained worldwide approval as nonnutritive sweeteners by the Joint Food and Agriculture Organization/World Organization Expert Committee on Food Additives. Cheminformatic tools suggested that the aglycone steviol and several of its phase I metabolites were predicted as potential anticonvulsant agents effective in the seizure animal model maximal electroshock seizure (MES) test. Thus, aqueous infusion from S. rebaudiana was tested in the MES test (mice, intraperitoneal administration), confirming dose-dependent anticonvulsant effect. Afterward, isolated stevioside and rebaudioside A were tested in the MES test, with positive results. Though drug repositioning most often focuses on known therapeutics, this article illustrates the possibilities of this strategy to find new functionalities and therapeutic indications for food constituents and natural products.

  2. Computer-Aided Identification of Anticonvulsant Effect of Natural Nonnutritive Sweeteners Stevioside and Rebaudioside A

    Science.gov (United States)

    Di Ianni, Mauricio E.; del Valle, Mara E.; Enrique, Andrea V.; Rosella, Mara A.; Bruno, Fiorella; Bruno-Blanch, Luis E.

    2015-01-01

    Abstract Steviol glycosides are natural constituents of Stevia rebaudiana (Bert.) Bert. (Asteraceae) that have recently gained worldwide approval as nonnutritive sweeteners by the Joint Food and Agriculture Organization/World Organization Expert Committee on Food Additives. Cheminformatic tools suggested that the aglycone steviol and several of its phase I metabolites were predicted as potential anticonvulsant agents effective in the seizure animal model maximal electroshock seizure (MES) test. Thus, aqueous infusion from S. rebaudiana was tested in the MES test (mice, intraperitoneal administration), confirming dose-dependent anticonvulsant effect. Afterward, isolated stevioside and rebaudioside A were tested in the MES test, with positive results. Though drug repositioning most often focuses on known therapeutics, this article illustrates the possibilities of this strategy to find new functionalities and therapeutic indications for food constituents and natural products. PMID:26258457

  3. Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent

    Directory of Open Access Journals (Sweden)

    Shakya Ashok K.

    2016-09-01

    Full Text Available A series of N-(2-(benzoyl/4-chlorobenzoyl-benzofuran- 3-yl-2-(substituted-acetamide derivatives (4a-l, 5a-l was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(cyclohexyl( methyl amino-acetamide] (5i and [N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(4-methylpiperidin-1- yl-acetamide] (5c demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(4-(furan-2-carbonyl-piperazin-1-yl-acetamide] (5f exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1 body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

  4. Mechanisms underlying the benefits of anticonvulsants over lithium in the treatment of bipolar disorder.

    Science.gov (United States)

    Corrado, Alisa C; Walsh, John P

    2016-02-10

    Close to 3% of the world's population suffers from bipolar disease (I and II). Of this 3%, bipolar disease affects largely women (∼ 3 : 2 compared with men). The median age of diagnosis is 25 in women and even lower in men. A diagnosis of bipolar disease is an expensive psychiatric diagnosis, costing patients more than twice as much money as a diagnosis of unipolar depression. Bipolar I is characterized by one or more manic or mixed episodes, with both mania and depression occurring each day for at least 1 week, whereas bipolar II is characterized by one or more major depressive episode and at least one episode of hypomania. Bipolar I is the more severe diagnosis. A wide range of medications are available to help patients maintain a healthy lifestyle, including lithium, antidepressants, and anticonvulsants. Improved methods for identifying bipolar disease, including a more structured approach and a more complete use of medical records, have increased the rate of diagnosis, especially in children, which underscores the need for innovation in development and in practice of new treatment options for treating bipolar disease. Although lithium has been the 'gold standard' for treating bipolar disorder for decades, new research into other forms of treatment has shown anticonvulsants to be a particularly useful therapy for treating bipolar disease. Anticonvulsants have remarkable mood-stabilization abilities and they do not lead to serious side effects, which increases the tolerability, and consequently, patient adherence to this form of treatment. Recent studies have shown that anticonvulsants improve behavior in bipolar disease by modulating the balance of excitatory and inhibitory synapses through a number of complementary molecular cascades that affect gene expression and cell survival.

  5. Evaluation of cytotoxicity and anticonvulsant activity of some Iranian medicinal Ferula species.

    Science.gov (United States)

    Bagheri, Seyyed Majid; Sahebkar, Amirhossein; Gohari, Ahmad Reza; Saeidnia, Soodabeh; Malmir, Maryam; Iranshahi, Mehrdad

    2010-03-01

    Several Ferula (Umbelliferae) species have been used in Iranian traditional medicine as antiflatulent, antispasmodic, anticonvulsant, expectorant, etc. In the present study, cytotoxicity and anticonvulsant activity of the methanol extracts from several Ferula species were evaluated. Air-dried samples of different parts of these plants (Ferula diversivittata Regel & Schmalh. (roots), Ferula persica Willd. (aerial parts), Ferula ovina (Boiss.) Boiss. (roots), Ferula badrakema Kos.-Pol. (roots), Ferula diversivittata (flowers), Ferula latisecta Rech. F. & Aell. (roots), and Ferula badrakema (fruits)) were macerated with methanol for 3 days. The mixtures were then filtered, concentrated and dried. For determination of the cytotoxicity of the extracts and also the oleo-gum-resin of F. assafoetida L., the brine shrimp (Artemia salina) was employed as a model assay system since it provides a convenient in-house pre-screening method for evaluating general cytotoxicity. The methanol extracts of different Ferula species and the oleo-gum-resin of F. assafoetida exhibited cytotoxic effect with LC(50) values in the range of 6-321 microg/mL. For the anticonvulsant testing, seizure was induced by injection of pentylenetetrazole (PTZ), 90 mg/kg intraperitoneally (i.p.). This dose was given to 10 groups, each consisting of 6 mice, which were pretreated i.p. with the extracts (300 mg/kg), Diazepam (10 mL/kg) or saline (10 mL/kg). The results showed that none of the tested Ferula species can prevent PTZ-induced seizure at the used dose. In conclusion, all of the extracts and the oleo-gum resin of F. assafoetida showed dose-dependent cytotoxicity which was highest in F. badrakema fruits and lowest in F. badrakema roots. Our findings also revealed that the methanol extracts and F. assafoetida oleo-gum resin do not possess anticonvulsant activity.

  6. Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats.

    Science.gov (United States)

    Shenoy, A K; Miyahara, J T; Swinyard, E A; Kupferberg, H J

    1982-08-01

    The 1.5-benzodiazepine (clobazam), the 1,4-benzodiazepine (diazepam), and two nonbenzodiazepine antiepileptic drugs (phenobarbital and valproate) were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that clobazam and valproate exhibit a wider range of experimental anticonvulsant activity than either diazepam or phenobarbital. Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine). Clobazam is effective by the MES test in rats only in doses that exceed the median minimal toxic dose. Phenobarbital is effective against all of the above tests, but minimal toxic doses must be employed to prevent strychnine seizures. Diazepam, on the other hand, is effective in nontoxic doses against seizures induced by Metrazol, bicuculline, and picrotoxin, but protects animals from maximal electroshock and strychnine seizures only when given in toxic doses. When compared on the basis of protective indices (PI = TD50/ED50) calculated from intraperitoneal data, the PIs for clobazam were 1.6 to 13 times higher than those for diazepam. Overall, except for the MES test in rats, the PIs for clobazam were from 1.5 to 44 times higher than those for any of the other three substances. With respect to the MES test in rats, the PI for clobazam was 10.8 times higher than that for diazepam; however, the PIs for phenobarbital and valproate were 3.5 and 4.4 times higher, respectively, than that for clobazam. These data suggest that the spectrum of anticonvulsant activity for the 1,5-benzodiazepine (clobazam) is superior to that for the 1,4-benzodiazepine (diazepam). Also, the broad experimental profile of anticonvulsant activity of clobazam agrees well with its reported broad clinical efficacy.

  7. Anticonvulsant profile and mechanism of action of propranolol and its two enantiomers.

    Science.gov (United States)

    Fischer, W

    2002-07-01

    The anticonvulsant properties of the ss-adrenoceptor antagonist propranolol and its two enantiomers were examined in various screening tests in order to characterize the anticonvulsant profile as well as the possible molecular mechanism of action. These compounds dose-dependently raised the threshold for tonic electroshock seizures in mice and were effective in the traditional maximal electroshock test (ED (50)s 15- 20 mg kg (-1)i.p.). In combination with clinically used antiepileptics, the anticonvulsant effectiveness of the latter was significantly increased. In the pentylenetetrazol (85 mg kg (-1)s.c.) seizure threshold test, ( +/-)- and ( +)-propranolol were not effective in preventing clonic seizures. In unrestrained rats with chronically implanted electrodes in the dorsal hippocampus, propranolol and its ( +)-enantiomer equieffectively reduced the duration of electrically-evoked hippocampal afterdischarges (10 and 20 mg kg (-1)i.p.) and raised the focal stimulation threshold (20 mg kg (-1)i.p.). In amygdala-kindled rats, both drugs ( >or= 10 mg kg (-1)i.p.) reduced the seizure severity from stage 5 (generalized clonic-tonic) to stage 3 (unilateral forelimb) seizures. Furthermore, whole-cell patch-clamp experiments showed that ( +)- as well as ( -)-propranolol ( 10(-6)to 10(-4)M) depressed the fast inward sodium current in a concentration- and use-dependent manner in cultured rat cardiomyocytes and inhibited picrotoxin-induced burst firing activity of mouse spinal cord neurones in culture. In conclusion, propranolol and its two enantiomers have anticonvulsant effects in models for generalized tonic-clonic and complex partial seizures which may be accounted for by the sodium channel blocking and not by the ss-adrenoceptor blocking activity.

  8. Radiological changes in the skeleton due to anticonvulsant therapy in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, R.; Heyer, R.; Freyschmidt, J.

    1981-01-01

    Anticonvulsant therapy can lead to severe rachitic changes in the skeleton which closely resemble renal osteopathy. In addition to apparent widening of the epiphyseal plate, there are changes in the cortex of the long bones. Within four to six weeks of the commencement of vitamin D therapy, recalcification of the poorly mineralised osteoid can be recognised. Since the changes are best seen in the hand, further examinations of the skeleton are only indicated if there are positive findings in the hand.

  9. Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism

    OpenAIRE

    Mandeep Kaur; Rajesh Kumar Goel

    2011-01-01

    “Ethnopharmacological” use of roots of Boerhaavia diffusa (B. diffusa) in the treatment of epilepsy in Nigerian folk medicine and reports showing the presence of a calcium channel antagonistic compound “liriodendrin” in its roots, led us to undertake the present study. The study was designed to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. A...

  10. Effect of electroconvulsive therapy without anticonvulsive premedication on serum growth hormone in man.

    Science.gov (United States)

    Vigas, M; Stowasserová, N; Németh, S; Jurcovicová, J

    1975-01-01

    Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed

  11. Anticonvulsant Effect of Guaifenesin against Pentylenetetrazol-Induced Seizure in Mice

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    Mojtaba Keshavarz

    2013-06-01

    Full Text Available Background: There have been some reports about the possible N-methyl-D-aspartate (NMDA antagonist activity of Guaifenesin. As drugs with a similar structure to Guaifenesin (i.e. Felbamate and those with NMDA antagonist activity have been clinically used as anticonvulsants, the aim of this study was to determine whether Guaifenesin has an anticonvulsant effect in an animal model of seizure. Methods: Anticonvulsant effect of Guaifenesin was assessed via Pentylenetetrazol (PTZ-induced convulsion. Male albino mice received Guaifenesin (100, 200, 300, or 400 mg/kg; n=8-10 or 0.25% Tween (vehicle intraperitoneally 30 minutes before the injection of PTZ (95 mg/kg. Diazepam (3 mg/kg; n=8 was used as a reference drug. The latency time before the onset of myoclonic, clonic, and tonic-clonic convulsions, percentage of animals exhibiting convulsion, and percentage of mortality were recorded. In addition, the effect of Guaifenesin on neuromuscular coordination was assessed using the Rotarod. Results: Guaifenesin at all the studied doses significantly increased the latency to myoclonic and clonic convulsions in a dose-dependent manner. In addition, Guaifenesin at the dose of 300 mg/kg increased the latency to tonic-clonic seizure. The ED50s of Guaifenesin for protection against PTZ-induced clonic and tonic-clonic seizures and death were 744.88 (360-1540, 256 (178-363, and 328 (262-411 mg/kg, respectively. Guaifenesin at all the investigated doses significantly reduced neuromuscular coordination, compared to the vehicle-treated group.Conclusion: These results suggest that Guaifenesin possesses muscle relaxant and anticonvulsant properties and may have a potential clinical use in absence seizure.

  12. Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.

    Science.gov (United States)

    Gold, P W; Pavlatou, M G; Michelson, D; Mouro, C M; Kling, M A; Wong, M-L; Licinio, J; Goldstein, S A

    2015-06-02

    Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age.

  13. Metabolic stability of new anticonvulsants in body fluids and organ homogenates.

    Science.gov (United States)

    Marszałek, Dorota; Goldnik, Anna; Pluciński, Franciszek; Mazurek, Aleksander P; Jakubiak, Anna; Lis, Ewa; Tazbir, Piotr; Koziorowska, Agnieszka

    2012-01-01

    The stability as a function of time of compounds with established anticonvulsant activity: picolinic acid benzylamide (Pic-BZA), picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA), picolinic acid 3-fluorobenzylamide (Pic-3-F-BZA), picolinic acid 4-fluorobenzylamide (Pic-4-F-BZA) and picolinic acid 2-methylbenzylamide (Pic-2-Me-BZA) in body fluids and homogenates of body organs were determined after incubation. It was found that they decompose relatively rapidly in liver and kidney and are stable against enzymes present in body fluids and some organs. These results are consistent with the bond strength expressed as total energy of amide bonds (calculated by quantum chemical methods) in the studied anticonvulsants. The calculated values of the amide bond energy are: 199.4 kcal/mol, 200.2 kcal/mol, 207.5 kcal/mol, 208.4 kcal/mol and 198.2 kcal/mol, respectively. The strength of the amide bonds in the studied anticonvulsants correctly reflects their stability in liver or kidney.

  14. Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs.

    Science.gov (United States)

    Stamp, T C; Round, J M; Rowe, D J; Haddad, J G

    1972-10-07

    Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0.001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 mug daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized.

  15. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

    Science.gov (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

    2013-12-01

    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs.

  16. Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat.

    Science.gov (United States)

    Amano, K; Katsuragi, S; Takamatsu, J; Ogata, A; Miyazaki, C; Deshimaru, M; Miyakawa, T

    2001-07-20

    The characteristics of the development of tolerance to the anticonvulsant effects of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid-kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5 mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to the anticonvulsant effect of dipotassium clorazepate developed in seizure stage on day 6, after-discharge duration on day 7 and seizure latency on day 4. In contrast, tolerance to the effects of diazepam developed more rapidly in seizure stage on day 4, after-discharge duration on day 4 and seizure latency on day 3. Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr after cessation of the administration of dipotassium clorazepate and diazepam. Concomitant determinations of plasma concentrations of the main metabolite of dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical difference during treatment, suggesting that the developed tolerance was not metabolic but functional.

  17. Stereoselective pharmacokinetics of stiripentol: an explanation for the development of tolerance to anticonvulsant effect.

    Science.gov (United States)

    Arends, R H; Zhang, K; Levy, R H; Baillie, T A; Shen, D D

    1994-06-01

    An earlier pharmacodynamic study of the chiral antiepileptic drug stiripentol in an intravenous pentylenetetrazol-induced seizure model in the rat showed the development of a significant degree of tolerance to the anticonvulsant and neurotoxic effects following subacute treatment with the racemic compound. A more recent study with the pure enantiomers of stiripentol indicated that the (+)-enantiomer is 2.4 times more potent than the (-)-enantiomer, based on a comparison of brain EC50 values for the anticonvulsant effect. Moreover, (-)-stiripentol has a much longer elimination half-life than (+)-stiripentol. We have re-analyzed the brain and blood samples from the first pharmacodynamic study using a newly developed chiral HPLC assay to investigate whether the tolerance phenomenon with racemic stiripentol was due to a shift in the enantiomeric composition of stiripentol in brain tissue during repetitive administration of racemic drug. A large increase, as much as 5-6-fold, in the (-)/(+) ratio in brain concentration of stiripentol was observed after subacute administration, as compared with that after a single dose of the racemic drug. The enrichment in the less potent enantiomers during repetitive drug administration explains the previous observation of an apparent development of tolerance when the pharmacologic effects were related to total [(-)+(+)] brain concentrations of stiripentol as measured by a non-stereoselective assay. The results of this study highlight the importance of stereoselective pharmacokinetics in investigating the pharmacodynamics of the racemic mixture of a chiral anticonvulsant.

  18. Evaluation of anticonvulsant activity of ethanolic leaves extract of Desmodium triflorum in mice

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    Girish Gowda

    2012-06-01

    Full Text Available The present investigation was aimed to study an anticonvulsant activity of ethanolic extract of Desmodium triflorum (L. DC., Fabaceae, in mice. Animal models of epilepsy namely the pentylenetetrazole (PTZ, isoniazid or isonicotinic hydrazide (INH and maximal electroshock induced convulsion (MES were used to evaluate the anticonvulsant effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH. In the PTZ induced convulsion, ethanolic extract of D. triflorum (EEDT 400 mg/kg significant delayed the onset of convulsion, reduced the duration of convulsion and reduced mortality. Similarly a dose of 800 mg/kg of EDDT significantly delayed the onset of convulsion, reduced the duration of convulsion and showed 33.33% protection in mice against INH induced convulsion. Further no mortality was found. Both the doses reduced hind limb tonic extension (HLTE phase of MES induced convulsion in mice. The pretreated EEDT showed significant inhibition of lipid peroxidation and increases the reduced glutathione level in mice brain tissue. The results revealed that D. triflorum possesses a significant dose dependent anticonvulsant activity.

  19. Reduced bone growth in rats treated with anticonvulsant drugs: a type II pseudohypoparathyroidism?

    Science.gov (United States)

    Robinson, P B; Harris, M; Harvey, W; Papadogeorgakis, N

    1982-01-01

    The effect of anticonvulsant drugs on bone growth and calcium metabolism was studied in Wistar strain rats. Animals were treated for 40-48 days with diphenylhydantoin (DPH) or sodium valproate (SV), or were thyroparathyroidectomized (TPTX) and maintained with thyroxine supplements. Bone growth, measured radiographically as increase in bone length, was reduced by up to 12% in the drug-treated and TPTX groups. Plasma iPTH concentrations were raised twofold- to threefold by DPH and SV. Total plasma calcium was not significantly altered in the DPH-treated rats but was elevated by SV treatment. Similarly, elevated iPTH and normal calcium values were also found in carbamazepine-treated and diazepam-treated rats in a separate experiment. Plasma alkaline phosphatase was reduced by high doses of the drugs. These results imply that anticonvulsant drugs induce end-organ resistance to PTH (a feature of pseudohypoparathyroidism), which may be responsible for some of the skeletal and dental abnormalities found in patients treated with anticonvulsants.

  20. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    Science.gov (United States)

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

  1. Bufo toxin: A new testing prospect for the screening of anti-convulsant agents. A review

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    David Arome

    2014-07-01

    Full Text Available Epilepsy is a common neurological disorder with diverse aetiology, affecting approximately 1 % of the entire population. Epilepsy present wide range of clinical manifestations, that affect the way a person feels and acts for a short time. Previous scientific investigations have indicated bufo toxin as a potential convulsant candidate that produced similar effects as other known convulsant agents. Bufo toxin has been shown to mimic or exhibit similar action as other known convulsant agent. Its biochemical components are formed as a result of the binding of bufo-fagin and a molecule arginina. There exist wide array of convulsant agents used in the screening of anti-convulsant agents. The commonly used one are: bicuculline, picrotoxin, pentylene tetrazole, isonizid etc. However, these agents are expensive, not easily available and affordable. This challenge prompted the search of other alternative convulsant agents that is easily accessible for use in the screening of anti-convulsant agents. The principal objective of this review paper is to suggest the possible use of bufo toxin which mimics the action of existing convulsant agents. This new testing convulsant agent (bufo toxin is inexpensive, affordable and easy to use when compared to other known convulsant agents. The experimental procedure is easy and it gives a broad spectrum in comparing the action of bufo toxin to other chemical convulsant agents. It also offers researchers broader view or options in exploring the anti-convulsant activity of test agents and the understanding of their possible mechanism of action.

  2. Application of Green Chemistry Principle in Synthesis of Phenytoin and Its Biogical Evaluation as Anticonvulsant Agents

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    Abhijit Kadam

    2011-01-01

    Full Text Available Phenytoin (5,5'-dipenylimidazolidine-2,4-dione is the prime example of anticonvulsant agent. According to reported procedure, it is synthesized by condensation of benzil and urea in presence of base (30% w/v NaOH using ethanol as solvent which itself acts as CNS stimulant. Removal of solvent after synthesis is most difficult and non-assured process. In case of phenytoin transformation in polymorphism plays an important role when solvent other than water is used. About 30% extra cost is calculated if solvent other than water is used. Therefore by application of green chemistry principle phenytoin was synthesized by condensation of benzil and urea in presence of base (30% NaOH and water as green solvent. This compound was characterized on the basis of its spectral (IR, 1H NMR data and evaluated for anticonvulsant activity using MES induced and PTZ induced seizure models in Swiss albino mice. Significant anticonvulsant activity was found by using 25 mg/kg and 50 mg/kg of phenytoin compared with standard phenytoin at 25 mg/kg dose.

  3. Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors.

    Science.gov (United States)

    Talevi, Alan; Enrique, Andrea V; Bruno-Blanch, Luis E

    2012-06-15

    A virtual screening campaign based on application of a topological discriminant function capable of identifying novel anticonvulsant agents indicated several widely-used artificial sweeteners as potential anticonvulsant candidates. Acesulfame potassium, cyclamate and saccharin were tested in the Maximal Electroshock Seizure model (mice, ip), showing moderate anticonvulsant activity. We hypothesized a probable structural link between the receptor responsible of sweet taste and anticonvulsant molecular targets. Bioinformatic tools confirmed a highly significant sequence-similarity between taste-related protein T1R3 and several metabotropic glutamate receptors from different species, including glutamate receptors upregulated in epileptogenesis and certain types of epilepsy.

  4. Canine Pancreas-Specific Lipase and C-reactive Protein in Dogs Treated With Anticonvulsants (Phenobarbital and Potassium Bromide).

    Science.gov (United States)

    Albarracín, Viviana; Teles, Mariana; Meléndez-Lazo, Antonio; Rodón, Jaume; Pastor, Josep

    2015-06-01

    Animals treated with anticonvulsant drugs may have increased canine pancreas-specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C-reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C-reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI.

  5. Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of acute phenytoin.

    Science.gov (United States)

    Gilbert, T H; Bharadia, V; Teskey, G C

    2001-10-01

    This study addressed some of the controversial issues surrounding the anticonvulsant effect of phenytoin, and the predictive validity of the guinea-pig kindling model for the screening of anticonvulsant drugs. Following an intraperitoneal injection of either 50 or 75 mg/kg phenytoin, we analysed plasma concentrations of phenytoin at various time intervals. Behavioural toxicity was assessed at 0.5 h postinjection using quantitative locomotor tests, as well as scores on a sedation/muscle relaxation rating index. The anticonvulsant efficacy of phenytoin was evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD) and behavioural seizure severity at three phases of kindling: non-kindled, kindling acquisition (early and late) and kindled (50+ ADs). ADD and seizure severity were also measured in response to both threshold and suprathreshold kindling stimulation. Plasma levels of phenytoin corresponded to the human therapeutic range at the time of behavioural testing and kindling. Phenytoin did not exert significant adverse effects in guinea-pigs on both the behavioural tests and rating index. Phenytoin increased ADT in non-kindled and kindled guinea-pigs and effectively reduced ADD and seizure severity, indicating that the guinea-pig model correctly predicted phenytoin's anticonvulsant effect. Phenytoin produced reliable anticonvulsant activity in the guinea-pig at threshold stimulation but a somewhat reduced efficacy on seizure severity at suprathreshold stimulation intensities. Kindling in the guinea-pig is a valid model of human partial seizures.

  6. Investigating the Anticonvulsant Effects of Repetitive Transcranial Magnetic Stimulation on Perforant Path Kindling Model in Rats

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    Ali Yadollahpour

    2015-02-01

    Full Text Available Background: Almost 20% of epileptics are drug resistant. Studies have shown that low frequency repetitive transcranial magnetic stimulation (rTMS is with therapeutic effects on epilepsy-affected laboratory models. Anticonvulsant effects of rTMS depend on several parameters among which radiation frequency is the most important one. In this study, the therapeutic impacts of 1 and 2 Hz rTMS on convulsing parameters in epileptic model of electrical kindling stimulation of the perforant path were investigated. Materials and Methods: In this experimental study 21 rats were randomly divided into three groups, namely ‘1 Hz treatment group’ and ‘2 Hz treatment group’ and ‘kindling group’. The kindling group only received kindling stimulations for seven days. One Hz and 2 Hz frequency treatment groups received maximally 5 min rTMS after termination of kindling stimulation per day for a week. Stimulation and stability electrodes had been placed, in turn, on perforant path and dentate gyrus. For quantifying the duration of the subsequent discharge waves, two-way ANOVA test and Bonferroni post-test were employed. In addition, for quantifying the convulsive behaviors, Kruskal-Wallis and the Mann-Whitney U tests were used. Results: The results showed that 1 Hz and 2 Hz frequency rTMS have considerable inhibitory impact on the development of convulsive phases. Anticonvulsive effect was observed from the first day after rTMS was undertaken. In addition, the animals did not show fourth and fifth convulsive stages, and a significant reduction was evident in their recorded peak discharge waves compared with kindle group. Conclusion: Low frequency rTMS possesses significant anticonvulsive effects which depend upon sTMS stimulation frequency.

  7. The potential anticonvulsant activity of the ethanolic extracts of Achillea nobilis and Momordica charantia in rats

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    Gamal A. Soliman

    2016-06-01

    Full Text Available Context: Currently available antiepileptic drugs have debilitating adverse effects. Natural products and plants already used in traditional medicine can be a good place to start in the search for safer and more effective options. Aims: To investigate the anticonvulsant potential of Achillea nobilis and Momordica charantia extracts in maximal electroshock (MES, as well as pentylenetetrazole (PTZ- and strychnine nitrate (STN- induced seizure models in rats. Methods: For each model, eight groups of 21-day-old male Albino rats were used. The 1st group was kept as control, 2nd as standard (diazepam, 7.5 mg/kg; 3rd – 5th treated with A. nobilis (100, 200 and 300 mg/kg; and 6th – 8th administered M. charantia (100, 200 and 300 mg/kg. After 30 min, rats were exposed to a shock of 150 mA by a convulsiometer, via ear electrodes for 2 s (in MES test or sc injection of PTZ (85 mg/kg or STN (2.5 mg/kg. Results: A. nobilis and M. charantia extracts (200 and 300 mg/kg demonstrated dose-dependent anticonvulsant effect against MES-induced seizures. In the PTZ induced convulsion, A. nobilis and M. charantia (200 and 300 mg/kg significantly slowed the commencement of convulsions and minimized the duration of seizures. A. nobilis (300 mg/kg showed 60% protection in rats against STN induced seizures. In contrast, A. nobilis (100 and 200 mg/kg and M. charantia (100, 200 and 300 mg/kg showed no significant protection against STN-induced seizures in rats. Conclusions: The results of the present study suggest that both extracts exhibited marked anticonvulsant activities.

  8. Tolerance to the anticonvulsant effect of clorazepate and clonazepam in mice.

    Science.gov (United States)

    Scherkl, R; Kurudi, D; Frey, H H

    1988-01-01

    The rate of development of tolerance to the benzodiazepines clorazepate and clonazepam against pentetrazole-induced seizures in mice was compared. Treatment with clorazepate (0.1% solution as drinking water) for 21 days led to tolerance beginning at day 7. When mice were treated with clonazepam (0.5 mg/kg twice daily intraperitoneally), tolerance was evident already at the fourth day of treatment. Twenty-four hours after cessation of treatment the seizure threshold was significantly decreased after treatment with both drugs. Clorazepate, a prodrug of the main metabolite of diazepam, desmethyldiazepam, regards further interest for anticonvulsant therapy because of a relatively slow onset of tolerance.

  9. Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol.

    Science.gov (United States)

    Fischer, W; Kittner, H; Regenthal, R; Malinowska, B; Schlicker, E

    2001-02-01

    Clenbuterol, a lipophilic beta2-adrenoceptor agonist, was investigated in various seizure models of experimental epilepsy. In the maximal electroshock seizure threshold test, clenbuterol (> or =4 mg/kg i.p.) increased the electroconvulsive threshold for tonic seizures in mice. In the traditional maximal electroshock seizure (MES) test in mice, ED50 values of 11 mg/kg i.p. or s.c. were determined. In both models, the beta2-receptor antagonist ICI 118.551 did not antagonize the anticonvulsant activity of clenbuterol. Combinations of clenbuterol with standard antiepileptics revealed additive anticonvulsant effects. Repeated administration of clenbuterol (5 mg/kg s.c., twice daily for 14 days) to mice did not significantly influence its anticonvulsant potency or the effectiveness of phenobarbital in the MES test. In various chemically-induced seizure tests with tonic convulsions, clenbuterol inhibited or tended to suppress the tonic phase. However, this drug was not effective in preventing clonic seizures in the pentylenetetrazol (85 mg/kg s.c.) seizure threshold test. In the rotarod ataxia test (mice), a minimal "neurotoxic" dose (TD50) of 41 mg/kg i.p. was determined. In unrestrained rats with chronically implanted electrodes in the dorsal hippocampus, clenbuterol (2 mg/kg and 4 mg/kg i.p.) significantly reduced the duration of electrically evoked hippocampal afterdischarges. In amygdala-kindled rats, clenbuterol (5 mg/kg and 10 mg/kg i.p.) reduced the seizure severity to stage 3. Additional studies indicated that clenbuterol (6 mg/kg i.p.) increased the heart rate and decreased the blood pressure, but this drug did not alter the plasma level of the two tested antiepileptics phenobarbital and carbamazepine. Furthermore, in whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes, clenbuterol (1-100 microM) depressed the fast sodium current in a concentration- and frequency-dependent manner. In conclusion, the anticonvulsant effects of higher doses

  10. A computational quantitative structure-activity relationship study of carbamate anticonvulsants using quantum pharmacological methods.

    Science.gov (United States)

    Knight, J L; Weaver, D F

    1998-10-01

    A pattern recognition quantitative structure-activity relationship (QSAR) study has been performed to determine the molecular features of carbamate anticonvulsants which influence biological activity. Although carbamates, such as felbamate, have been used to treat epilepsy, their mechanisms of efficacy and toxicity are not completely understood. Quantum and classical mechanics calculations have been exploited to describe 46 carbamate drugs. Employing a principal component analysis and multiple linear regression calculations, five crucial structural descriptors were identified which directly relate to the bioactivity of the carbamate family. With the resulting mathematical model, the biological activity of carbamate analogues can be predicted with 85-90% accuracy.

  11. Sleep EEG Power Spectral Profiles and Anticonvulsant Drugs: Comparison of Protective Effects with Monomethylhydrazine.

    Science.gov (United States)

    1982-04-01

    anticonvulsant drugs produced a specific pattern of spectral density change localized to sensorimotor cortex, bilater- ally. This consisted of a sharp...0102 LF 014 6601 SECURITY CLASSIFICATION OF THIS PAGE (M~en Deie bIofed ) 20 (continued) in the 12-15 Hz band. A seund ;dentlLal test series was...with pyridoxine and di- azepain but not with vaiproic dLid o’" Cdr*bd111dzep1nre. Reference to the spectral density changes produced by these groups of

  12. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S;

    1999-01-01

    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GABA...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  13. Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling.

    Science.gov (United States)

    Jeffrey, M; Lang, M; Gane, J; Chow, E; Wu, C; Zhang, L

    2014-01-17

    Progesterone is a known anticonvulsant, with its inhibitory effects generally attributed to its secondary metabolite, 5α,3α-tetrahydroprogesterone (THP), and THP's enhancement of GABAA receptor activity. Accumulating evidence, however, suggests that progesterone may have non-genomic actions independent of the GABAA receptor. In this study, we explored THP/GABAA-independent anticonvulsive actions of progesterone in a mouse model of hippocampal kindling and in mouse entorhinal slices in vitro. Specifically, we examined the effects of progesterone in kindled mice with or without pretreatments with finasteride, a 5α-reductase inhibitor known to block the metabolism of progesterone to THP. In addition, we examined the effects of progesterone on entorhinal epileptiform potentials in the presence of a GABAA receptor antagonist picrotoxin and finasteride. Adult male mice were kindled via a daily stimulation protocol. Electroencephalographic (EEG) discharges were recorded from the hippocampus or cortex to assess "focal" or "generalized" seizure activity. Kindled mice were treated with intra-peritoneal injections of progesterone (10, 35, 100 and 160mg/kg) with or without finasteride pretreatment (50 or 100mg/kg), THP (1, 3.5, 10 and 30mg/kg), midazolam (2mg/kg) and carbamazepine (50mg/kg). Entorhinal cortical slices were prepared from naïve young mice, and repetitive epileptiform potentials were induced by 4-aminopyridine (100μM), picrotoxin (100μM) and finasteride (1μM). Pretreatment with finasteride did not abolish the anticonvulsant effects of progesterone. In finasteride-pretreated mice, progesterone at 100 and 160mg/kg decreased cortical but not hippocampal afterdischarges (ADs). Carbamazepine mimicked the effects of progesterone with finasteride pretreatments in decreasing cortical discharges and motor seizures, whereas midazolam produced effects similar to progesterone alone or THP in decreasing hippocampal ADs and motor seizures. In brain slices, progesterone

  14. Anticonvulsant potential of ethanol extracts and their solvent partitioned fractions from Flemingia strobilifera root

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    Kavita Gahlot

    2013-01-01

    Full Text Available Background: Flemingia strobilifera (FS R.Br. (Fabaceae is an important medicinal plant. In wealth of India it has been reported that roots of FS are used by santals in epilepsy, hysteria, insomnia, and to relieve pain. In Burma also the roots of F. strobilifera are used to treat epilepsy. Objective: To investigate anticonvulsant potential of 95% ethanol extract and four subsequent fractions (petroleum ether, chloroform, ethyl acetate, and aqueous fractions of the roots of FS against pentylenetetrazole (PTZ and maximal electroshock (MES induced convulsions. Material and Methods: All the fractions and crude ethanol extract were administered (i.e., 200, 400, 600 mg/kg, p.o. for 7 days and at the end of the treatment convulsions were induced experimentally using pentylenetetrazole and Maximal electroshock Test. Diazepam and phenytoin (4 mg/kg, i.p. and 20 mg/kg, i.p., respectively were used as reference anticonvulsant drugs against experimentally induced convulsions. The latency of tonic convulsions and the numbers of animals protected from tonic convulsions were noted. Results: High doses (200 and 300 mg/kg, p.o. of ethyl acetate fraction and 95% ethanol crude extract (400 and 600 mg/kg, p.o. significantly reduced the duration of seizure induced by maximal electroshock (MES. The same dose also protected from pentylenetetrzole-induced tonic seizures and significantly delayed the onset of tonic seizures. However, pet, ether, chloroform, and aqueous fraction at any of the doses used (i.e., 100, 200, 300 mg/kg, p.o. did not show any significant effect on PTZ and MES induced convulsions. The treatment with crude ethanolic extract and ethyl acetate fraction caused signs of central nervous system depressant action in the locomotor activity test, confirmed by the potentiation of sodium pentobarbital sleeping time. Both did not cause disturbance in motor coordination assessed by rotarod test. Conclusion: The data suggest that crude ethanol extract and ethyl

  15. Anticonvulsant activity of gap-junctional blocker carbenoxolone in albino rats

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    Suneel Kumar Reddy

    2014-08-01

    Conclusions: Carbenoxolone has in-vivo anticonvulsive effect and could be useful in both petitmal (absence seizures and grand mal (generalized tonic-clonic epilepsy seizures. The protective effect of carbenoxolone could be due to blockade of GJ channels that mediate electro tonic coupling and thereby prevent the neural synchronization that is characteristic of seizures. The study also supports the view that GJs have a functional role in the electrophysiology of seizures and GJ blockers have potential as a new class of antiepileptic drugs. [Int J Basic Clin Pharmacol 2014; 3(4.000: 711-717

  16. Synthesis and anticonvulsant activity of 1-substituted benzyl-N-substituted-1, 2, 3-triazole-4-for-mamides

    Institute of Scientific and Technical Information of China (English)

    WANG Junmin; JUN Changsoo; CHAI Kyuyun; KWAK Kyungchell; QUAN Zheshan

    2006-01-01

    Substituted benzyl azids were synthesized through the reaction of substituted benzyl chloride and sodium azid, which subsequently underwent cyclization with ethyl propiolate and amidation to give thirteen 1-substituted benzyl-N-substituted-1, 2, 3-triazole-4-formamide derivatives (3a-3m). The structure of the synthesized compounds was confirmed by IR, 1H-NMR, MS and elemental analysis. Their anticonvulsant activity against maximal electrolshock (MES) induced seizure was tested and the result showed that all these compounds possess anticonvulsant activity in different degrees. Among those, the compounds containing chloro atoms on the phenyl ring were less potent in anticonvulsant activity, while introducing one or two fluorin atoms on benzyl system increased its activity. Furthermore, their activity decreased when there was substituent on the nitrogen atom of carboxamide, and the larger the substituent, the lower the activity.

  17. Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants.

    Science.gov (United States)

    Gitto, Rosaria; De Luca, Laura; Ferro, Stefania; Agnello, Stefano; Russo, Emilio; De Sarro, Giovanbattista; Chimirri, Alba

    2010-12-01

    We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.

  18. Anticonvulsant and antioxidant activity of aqueous leaves extract of Desmodium triflorum in mice against pentylenetetrazole and maximal electroshock induced convulsion

    Directory of Open Access Journals (Sweden)

    Vaibhav Bhosle

    2013-08-01

    Full Text Available The present investigation was aimed to study an anticonvulsant activity of aqueous extract of Desmodium triflorum (L. DC., Fabaceae, in mice. Animal models of epilepsy namely the pentylenetetrazole, and maximal electroshock induced convulsion were used to evaluate the anticonvulsant effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione. In the pentylenetetrazole induced convulsion, aqueous extract of D. triflorum 800 mg/kg significant delayed the onset of convulsion, reduced the duration of convulsion (p<0.05 and reduced mortality. The aqueous extract of D. triflorum 800 mg/kg dose reduced hind limb tonic extension phase of maximal electroshock induced convulsion induced convulsion in mice (p<0.05. The pretreated aqueous extract of D. triflorum showed significant inhibition of lipid peroxidation and increases the reduced glutathione level in mice brain tissue (p<0.001. The results revealed that D. triflorum possesses a significant dose dependent anticonvulsant activity.

  19. The perirhinal cortex of rats: an intricate area for microinfusion of anticonvulsants against soman-induced seizures.

    Science.gov (United States)

    Myhrer, Trond; Enger, Siri; Aas, Pål

    2013-01-01

    Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide cannula in each hemisphere only invades a small area of this seizure controlling site in rats exposed to soman. The purpose of the present study was to examine whether infusions made through 2 cannulas in each perirhinal cortex may produce more efficacious anticonvulsant action against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP. The results showed that the mere presence of indwelling double cannulas caused proconvulsant effect in response to subsequent systemic administration of soman. Both the control and caramiphen groups with double cannulas had significantly shorter latencies to seizure onset than the corresponding groups with single cannula. Procyclidine resulted in anticonvulsant efficacy, even in rats with double cannulas. In rats that received twin infusions of DCG-IV or MPEP, the anticonvulsant impact was very high, inasmuch as a majority of the rats in each group was protected against seizure activity. Drugs possessing powerful anticonvulsant potency can apparently counteract the proconvulsant effect of double cannulas, and some can even gain enhanced anticonvulsant capacity when invading a larger area of the perirhinal cortex. Perirhinal EEG recordings (electrodes in indwelling cannulas) in a separate set of rats not exposed to soman or drugs showed no differences in basal electrical activity (total power 0.5-25Hz or the theta band 4-12Hz) between groups with single or double cannulas. The intrinsic excitability and synaptic connectivity of the perirhinal cortex may be associated with the proconvulsant impact observed in rats with double cannulas when exposed to soman.

  20. A novel series of 2,5-disubstituted 1,3,4-thiadiazoles as potential anticonvulsant agent

    Institute of Scientific and Technical Information of China (English)

    Harish Rajak; Chinmay K. Behera; Rajesh S. Pawar; Pradeep K. Singour; Murli Dhar Kharya

    2010-01-01

    In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore, a series of novel N-({5-[(6-methyl-1-benzofuran-3-yl)methyl]-1,3,4-thiadiazol-2-yl}carba-mothioyl)-2/3/4-substitutedbenzamide were designed, synthesized and evaluated for their anticonvulsant activity. The findings of the present studies confirmed that the pharmacophore model with four binding sites is crucial for anticonvuisant activity. Structure-activity relationships among synthesized compounds were also established.

  1. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

    Directory of Open Access Journals (Sweden)

    Mansour Homayoun

    2015-04-01

    Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

  2. Childhood epilepsy and autism spectrum disorders: psychiatric problems, phenotypic expression, and anticonvulsants.

    Science.gov (United States)

    Robinson, Sally J

    2012-09-01

    Epilepsy and autism spectrum disorders (ASDs) frequently co-occur during childhood, however, the characteristics of psychiatric or behavioural problems in these children remains largely unknown. This article contributes to these discussions by reporting on the prevalence and presentation of psychiatric or behavioural problems in children with epilepsy and ASDs, as well as on the use of anticonvulsants in these children. The current evidence suggests that children with epilepsy and ASDs may present with a distinct clinical profile, with a greater number of developmental difficulties, and a more severe expression of the ASD phenotype that can not solely be accounted for by level of intellectual functioning. Positive effects of anticonvulsants on behavioural symptoms associated with ASDs were also reported, though pharmacoresistance and a lack of clear treatment guidelines may contribute to an elevated risk of adverse side effects. In relation to clinical presentation and management there is a need for careful consideration of potential interaction effects between disorder specific factors (e.g., age of seizure onset/ASD diagnosis), cognitive characteristics (e.g., intellectual functioning, memory), and psychosocial variables (e.g., coping strategies). Ultimately however, many conclusions are tentative and this review highlights the need for more empirically validated research on children with epilepsy and ASDs.

  3. Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Fielding, S.; Wilker, J.C.; Chernack, J.; Ramirez, V.; Wilmot, C.A.; Martin, L.L.; Payack, J.F.; Cornfeldt, M.L.; Rudolphi, K.A.; Rush, D.K. (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ (USA))

    1990-01-01

    8319, ((+-)-2-Amino-N-ethyl-alpha- (3-methyl-2-thienyl) benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced (3H) TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.

  4. Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats

    Institute of Scientific and Technical Information of China (English)

    DU Peng; TANG Hai-yan; LI Xin; LIN Hao-jie; PENG Wei-feng; MA Yu; FAN Wei; WANG Xin

    2012-01-01

    Background Curcumin,an active ingredient of turmeric with antioxidant and anti-inflammatory properties has recently been reported to have anticonvulsant effects in several animal models of epilepsy.This study aimed to investigate the effects of curcumin on the pilocarpine rat model of status epilepticus.Methods The effect of intraperitoneal administration of curcumin (30,100,and 300 mg/kg) on pilocarpine-induced seizures in rats was tested.The correlation between seizure activity and hippocampal levels of nitric oxide synthase and free radicals was quantified.Whether curcumin treatment modulated these parameters was also investigated.Results Curcumin significantly increased seizure threshold at doses of 100 and 300 mg/kg.Rats with pilocarpineinduced seizures showed significantly elevated levels of malonaldehyde,nitric oxide synthase,and lactate dehydrogenase,but decreased levels of superoxide dismutase and glutathione compared with normal control rats.At doses of 100 and 300 mg/kg,curcumin reversed the effects of pilocarpine-indUced seizures on nitric oxide synthase,lactate dehydrogenase,glutathione,and superoxide dismutase.However,curcumin did not restore the elevated malonaldehyde levels.Conclusion Curcumin has anticonvulsant activity in the pilocarpine rat model of seizures,and that modulation of free radicals and nitric oxide synthase may be involved in this effect.

  5. Influence of organic surface coatings on the sorption of anticonvulsants on mineral surfaces.

    Science.gov (United States)

    Qu, Shen; Cwiertny, David M

    2013-10-01

    Here, we explore the role that sorption to mineral surfaces plays in the fate of two commonly encountered effluent-derived pharmaceuticals, the anticonvulsants phenytoin and carbamazepine. Adsorption isotherms and pH-edge experiments are consistent with electrostatics governing anticonvulsant uptake on metal oxides typically found in soil and aquifer material (e.g., Si, Al, Fe, Mn, and Ti). Appreciable, albeit limited, adsorption was observed only for phenytoin, which is anionic above pH 8.3, on the iron oxides hematite and ferrihydrite. Adsorption increased substantially in the presence of cationic and anionic surfactants, species also commonly encountered in wastewater effluent. For carbamazepine, we propose the enhanced uptake results entirely from hydrophobic interactions with apolar tails of surfactant surface coatings. For phenytoin, adsorption also arises from the ability of surfactants to alter the net charge of the mineral surface and thereby further enhance favorable electrostatic interactions with its anionic form. Collectively, our results demonstrate that although pristine mineral surfaces are likely not major sinks for phenytoin and carbamazepine in the environment, their alteration with organic matter, particularly surfactants, can considerably increase their ability to retain these emerging pollutants in subsurface systems.

  6. Comparison of anticonvulsant tolerance, crosstolerance, and benzodiazepine receptor binding following chronic treatment with diazepam or midazolam.

    Science.gov (United States)

    Ramsey-Williams, V A; Wu, Y; Rosenberg, H C

    1994-07-01

    In a previous study, rats treated chronically with flurazepam were tolerant to the anticonvulsant action of some benzodiazepines (BZs), but not others (34). To determine if this differential crosstolerance was unique to flurazepam, rats were treated chronically with diazepam or midazolam, and tested for tolerance to the anticonvulsant actions of diazepam, midazolam, clonazepam, and clobazam. Regional benzodiazepine receptor binding in brain was also studied. In contrast to previous findings with flurazepam, 1 week treatment with diazepam or with midazolam did not cause tolerance. Rats treated with diazepam for 3 weeks were tolerant to diazepam, clonazepam, clobazam, and midazolam. In contrast, rats treated 3 weeks with midazolam were tolerant to diazepam and midazolam, but not clobazam or clonazepam. Neither diazepam nor midazolam treatment for 3 weeks altered BZ binding in cerebral cortex, cerebellum, or hippocampus. The effects of chronic BZ treatment depended not only on the BZ given chronically, but also on the BZ used to evaluate these effects, suggesting drug-specific interactions of different BZs with their receptors.

  7. Anxiolytic and anticonvulsant effects of dioclenol flavonoid isolated from stem bark of dioclea grandiflora on mice

    Directory of Open Access Journals (Sweden)

    E R De Almeida

    2009-12-01

    Full Text Available Summary: The aim of the present study is to demonstrate the anxiolitic and anticonvulsant effect of fraction (alcoholic obtained from the stem bark of Dioclea grandiflora (Dg and Dioclenol on mice using several behavioural assays. Groups of mice treated by the intraperitoneal (i.p. route with doses of 15, 30, and 60 mg/kg (i.p. of the fraction and Dioclenol with a dose of 10 mg / kg showed significant action in the Elevated Plus-maze (EPM (time spent in open arms and time in spent in the closed arms. The Hole-board Test also showed a significant increase in the time spent in the Head-dip and Marble-Burying Tests. The same treatment increased the duration of the sleeping time induced by Sodium Pentobarbital, and showed a significant increase in protection against Pentylenotetrazole induced convulsion. These results indicate an anxiolitic-like and anticonvulsant-like effect of the fraction of stem bark of Dg and Dioclenol in mice. The phytochemical analysis suggests that the alcoholic fraction has higher concentration of flavonoid active (Dioclenol and deserves further analysis. The studies conducted with the Dioclea grandiflora, can contribute, in the long term, in the field of its action in the CNS this flavonoid. Industrial relevance: The studies conducted with the Dioclea grandiflora, can contribute, in the long term, in the field of its action in the CNS.

  8. Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide

    Science.gov (United States)

    Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio E.; Anguiano-Robledo, Liliana; Soriano-Ursúa, Marvin A.; Correa-Basurto, José; Davood, Asghar; Chamorro-Cevallos, Germán

    2016-01-01

    Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP and Cl-HEPP) with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets—GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R-HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor. PMID:27006945

  9. Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

    Science.gov (United States)

    Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

    2015-04-01

    Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 μmol, whereas the additively calculated ED50add value was 0.49±0.03 μmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 μmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures.

  10. Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals

    Institute of Scientific and Technical Information of China (English)

    Musa Mumammad Aliyu; Abdullahi Ismail Musa; Muhammad Jaafar Kamal; Magaji Garba Mohammed

    2014-01-01

    Objective: To investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetula braunii, a plant used in ethnomedicine for the treatment of epilepsy. Methods:The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks, pentylenetetrazole and 4-aminopyridine-induced seizures in mice. Results: The preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins, carbohydrates, flavonoids, tannins, anthraquinones and steroids. Similarly, tannins, flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction. In the pharmacological screening, 150 mg/kg of the fraction protected 83.33% of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100% protection. In the 4-aminopyridine-induced seizure model, the fraction produced a significant (P Conclusions:These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.

  11. ANTICONVULSANT ACTIVITY OF DIVALPROEX SODIUM AND EFFECT OF GLIMEPIRIDE ON PHARMACOKINETIC: AN EXPERIMENTAL DRUG INTERACTION STUDY

    Directory of Open Access Journals (Sweden)

    SHYAM SHAH

    2016-10-01

    Full Text Available Background and Objectives: Epilepsy is a serious and common chronic neurological disorder caused by abnormal synchronized neuronal discharges. Divalproex is suggested to increase GABA concentration in brain. Both Divalproex and Glimepiride used for long duration indicate for CNS disorder and Diabetes mellitus. The study was conducted to find the influence of Glimepiride on pharmacokinetic and anticonvulsant activity of Divalproex.Methods: Four healthy rabbits of either sex were used to study the effect of Glimepiride on pharmacokinetic parameters of Divalproex. The concentration of Valproic acid (VPA in serum was estimated by HPLC coupled with Mass Spectroscopy (LC-MS/MS. Anticonvulsant activity was studied using Maximal Electroshock (MES method and Pentylenetetrazole (PTZ test in healthy albino rats.Results: The serum concentration of VPA was significantly increased after Glimepiride treatment for 7 days. Pharmacokinetic parameters like AUC, AUMC, T1/2 and Cmax of VPA showed significant change after Glimepiride treatment in healthy albino rabbits. Glimepiride also exhibited significant increase in duration of hind limb extensor time and onset of clonic convulsion time in MES and PTZ induced seizure test respectively. The percentage prolongation of onset of clonic convulsion was decreased to 49.6% in combination treatment. Conclusion: The drug-drug interaction between Divalproex and Glimepiride could be due to metabolism of both the drugs at the same site and protein binding to albumin.

  12. Screening of Careya arborea Roxb for their anticonvulsant properties in experimental animals

    Directory of Open Access Journals (Sweden)

    Gulab S Shinde

    2013-01-01

    Full Text Available Background: Bark of Careya arborea Roxb are traditionally used in the ayurvedic system of medicine for the treatment of epilepsy. Aims : The aim of the present study was to evaluate anticonvulsant activity of C. arborea Linn. bark against experimental induced seizures. Settings and Design: Convulsion was induced by maximal electroshock seizures (MES, pentylenetetrazol (PTZ and PTZ-induced kindling model. Materials and Methods: Petroleum ether (PE, chloroform (CH, methanol (ME and aqueous (AQ extract of C. arborea bark at 150 and 300 mg/kg b.w. were administered in all models. Statistical Analysis: Mean values and standard error mean was determined for all models and data was analyzed by one-way ANOVA, followed by Dunnett′s test. Results and Conclusion: The ME and AQ extract of C. arborea bark at 300 mg/kg b.w. p.o. showed the most significant ( P < 0.01 anticonvulsant effect by decreasing the duration of hind limb extension (extensor phase, clonus and also the duration of stupor phase, as compared with control in MES and PTZ and the extracts also inhibited seizure score in PTZ-induced kindling model.

  13. Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

    Science.gov (United States)

    Abdolmaleki, Arash; Moghimi, Ali; Ghayour, Mohammad B; Rassouli, Morteza B

    2016-10-15

    Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (PCiticoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (Pciticoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (Pciticoline significantly reduced the latency to sleep (Pciticoline has anticonvulsant activity and sedative effect.

  14. Microwave-assisted synthesis, anticonvulsant activity and quantum mechanical modelling of N-(4-bromo-3-methylphenyl)semicarbazones

    Institute of Scientific and Technical Information of China (English)

    SHALINI Mehta; YOGEESWARI Perumal; SRIRAM Dharmarajan; INDUJA Sridharan

    2007-01-01

    Objective: To study the effect of halo substitution on disubstituted aryl semicarbazones on the anticonvulsant potential and model the activity based on quantum mechanics. Methods: A series of twenty-six compounds of N4-(4-bromo-3-methylphenyl) semicarbazones were synthesized and evaluated for the anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential compounds were also tested in the subcutaneous strychnine (scSTY) and subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized compounds were tested for behavioral impairment and CNS (central nervous system) depression in mice. Quantum mechanical modelling was carried out on these compounds to gain understanding on the structural features essential for activity. Results: Some compounds possessed broad spectrum anticonvulsant activity as indicated by their effect in pentylenetetrazole, strychnine, picrotoxin and maximal electroshock seizures models in resemblance to other aryl semicarbazone derivatives reported earlier. The higher the difference in HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels was, the greater was the activity profile. Conclusion: The pharmacophoric requirements for compounds to exhibit anticonvulsant activity that includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an electron donor have been justified with the molecular orbital surface analysis of the synthesized compounds.

  15. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

    NARCIS (Netherlands)

    Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

    2014-01-01

    BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-gene

  16. Evaluation of anticonvulsant activity of volatile oil extract of Nigella sativa seeds by chemically induced seizure model in albino rats

    Directory of Open Access Journals (Sweden)

    Asmatanzeem Bepari

    2016-08-01

    Conclusions: The N. sativa seeds showed anticonvulsant activity in pentylenetetrazole induced seizure model of epilepsy. This study showed that volatile oil of N. sativa seeds potentiated the effect of sodium valproate. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1300-1307

  17. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  18. Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt Ant Venom (Formicidae: Ponerinae

    Directory of Open Access Journals (Sweden)

    Diana Aline Morais Ferreira Nôga

    2016-12-01

    Full Text Available Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt protects mice against bicuculline (BIC-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC resulting in six fractions referred to as DqTx1–DqTx6. A liquid chromatography-mass spectrometry (LC/MS analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM, DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.

  19. Pharmacokinetic profile of a new anticonvulsant, stiripentol, in the rhesus monkey.

    Science.gov (United States)

    Lin, H S; Levy, R H

    1983-12-01

    Stiripentol is a new anticonvulsant drug derived from phenyl-l-pentene-ol. One of its metabolites resulting from opening of the methylenedioxy ring also possesses anticonvulsant activity. This study undertook to define the overall pharmacokinetic profile of stiripentol in rhesus monkey prior to its efficacy evaluation. The experimental design included six treatments (three intravenous doses of 40, 80, and 120 mg; one oral dose of 80 mg; and two intraperitoneal doses of 80 and 120 mg) administered to five chaired rhesus monkeys in a randomized fashion. Sixteen plasma samples were obtained over 7 h and urine was collected for 24 h. A high-performance liquid chromatography assay was developed for the determination of stiripentol in plasma and urine (C8 reverse phase column and UV detection, lambda = 254 nm). The intravenous data revealed multiexponential behavior and therefore noncompartmental methods were used to describe the pharmacokinetics of stiripentol. Values for plasma clearances (L/h/kg) were 1.10 +/- 0.07 (40 mg), 0.92 +/- 0.08 (80 mg), and 0.86 +/- 0.15 (120 mg). The decrease in clearance with dose provided evidence of nonlinearity. The average mean residence time was 1.09 +/- 0.03 h. The average volume of distribution at steady state was 1.03 +/- 0.3 L/kg. The bioavailabilities obtained for the oral and intraperitoneal doses were consistent with first-pass effect predictions: 0.3 (oral), 0.32 (i.p. 80 mg), and 0.34 (i.p. 120 mg). The free fraction determined by equilibrium dialysis was less than 1%. The fraction of dose excreted unchanged in urine ranged between 0 and 3%. The metabolite with anticonvulsant activity could not be detected in plasma with any of the modes of administration. However, it was found in urine and accounted for 2% of the dose. The fraction metabolized by glucuronidation was 34.8 +/- 9.1%. The percentages of total amount of glucuronide excreted in the intervals 0-2, 2-4, 4-8, and 8-24 h were 70.6 +/- 6.2, 10.1 +/- 5.4, 13.6 +/- 5

  20. Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt) Ant Venom (Formicidae: Ponerinae).

    Science.gov (United States)

    Nôga, Diana Aline Morais Ferreira; Brandão, Luiz Eduardo Mateus; Cagni, Fernanda Carvalho; Silva, Delano; de Azevedo, Dina Lilia Oliveira; Araújo, Arrilton; Dos Santos, Wagner Ferreira; Miranda, Antonio; da Silva, Regina Helena; Ribeiro, Alessandra Mussi

    2016-12-23

    Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt) protects mice against bicuculline (BIC)-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC) resulting in six fractions referred to as DqTx1-DqTx6. A liquid chromatography-mass spectrometry (LC/MS) analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL) was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM), DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.

  1. Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice.

    Science.gov (United States)

    Zhou, Ziqi; Lin, Yanzhu; Zheng, Hongyi; He, Yuzhong; Xu, Haohua; Zhang, Siheng; Weng, Wen; Li, Wei; Zhu, Linyan; Yang, Haifeng

    2015-08-01

    Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. However, long-term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short-/long-term memory loss were observed in the PHT group, while the PHT + GD therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of NF-κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT-associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients.

  2. Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

    Science.gov (United States)

    Nikalje, Anna Pratima G; Ghodke, Mangesh; Girbane, Amol

    2012-01-01

    A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

  3. Synthesis and research of benzylamides of some isocyclic and heterocyclic acids as potential anticonvulsants.

    Science.gov (United States)

    Strupińska, Marzanna; Rostafińska-Suchar, Grazyna; Pirianowicz-Chaber, Elzbieta; Stables, James P; Jiang, Jeff; Paruszewski, Ryszard

    2013-01-01

    A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.

  4. (Biphenyl-4-yl)methylammonium chlorides: potent anticonvulsants that modulate Na+ currents.

    Science.gov (United States)

    Lee, Hyosung; Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T; Wilson, Sarah M; Khanna, Rajesh; Kohn, Harold

    2013-07-25

    We have reported that compounds containing a biaryl linked unit (Ar-X-Ar') modulated Na(+) currents by promoting slow inactivation and fast inactivation processes and by inducing frequency (use)-dependent inhibition of Na(+) currents. These electrophysiological properties have been associated with the mode of action of several antiepileptic drugs. In this study, we demonstrate that the readily accessible (biphenyl-4-yl)methylammonium chlorides (compound class B) exhibited a broad range of anticonvulsant activities in animal models, and in the maximal electroshock seizure test the activity of (3'-trifluoromethoxybiphenyl-4-yl)methylammonium chloride (8) exceeded that of phenobarbital and phenytoin upon oral administration to rats. Electrophysiological studies of 8 using mouse catecholamine A-differentiated cells and rat embryonic cortical neurons confirmed that 8 promoted slow and fast inactivation in both cell types but did not affect the frequency (use)-dependent block of Na(+) currents.

  5. Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

    Science.gov (United States)

    Matsumura, Nobuko; Nakaki, Toshio

    2014-10-15

    The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs.

  6. Phytochemical investigation characterisation and anticonvulsant activity of Ricinus communis seeds in mice.

    Science.gov (United States)

    Tripathi, Avinash Chandra; Gupta, Rajiv; Saraf, Shailendra K

    2011-11-01

    The ethanol extract of the dried, powdered hull portion of Ricinus communis seeds indicated the presence of alkaloids, steroids, flavonoids, glycosides and phenolics, amongst others. Ricinine was isolated as an active constituent and characterised by various chemical and spectroscopic techniques. The anticonvulsant activity of the isolated compound was evaluated in mice using the maximal electroshock (MES) model. The isolated compound at a dose of 60 mg kg⁻¹ body weight, orally, significantly (p < 0.05) reduced the extensor tonus phase of convulsion by MES-induced seizures in albino mice when compared with the standard drug diazepam (30 mg kg⁻¹ body weight, orally). The results of this study support the folkloric use of the plant in epileptic remedies.

  7. Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Gerds, Thomas Alexander; Feldt-Rasmussen, Bo

    2015-01-01

    IMPORTANCE: Lithium is the main mood stabilizing drug for bipolar disorder. However, it is controversial whether long-term maintenance treatment with lithium or other drugs for bipolar disorder causes chronic kidney disease (CKD). OBJECTIVE: To compare rates of CKD and in particular rates of end......-stage CKD among individuals exposed to successive prescriptions of lithium, anticonvulsants, or other drugs used for bipolar disorder. DESIGN, SETTING, AND PARTICIPANTS: This is a Danish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals...... included the subgroup of 10 591 patients diagnosed as having bipolar disorder. MAIN OUTCOMES AND MEASURES: Possible CKD, definite CKD, and end-stage CKD (defined as long-term dialysis or renal transplantation). RESULTS: A total of 14 727 (0.8%), 18 762 (1.0%), and 3407 (0.2%) in cohort 1 and 278 (2...

  8. Trends in resource utilization and prescription of anticonvulsants for patients with active epilepsy in Germany.

    Science.gov (United States)

    Strzelczyk, Adam; Haag, Anja; Reese, Jens P; Nickolay, Tanja; Oertel, Wolfgang H; Dodel, Richard; Knake, Susanne; Rosenow, Felix; Hamer, Hajo M

    2013-06-01

    This study evaluated trends in the resource use of patients with active epilepsy over a 5-year period at an outpatient clinic of a German epilepsy center. Two cross-sectional cohorts of consecutive adults with active epilepsy were evaluated over a 3-month period in 2003 and 2008. Data on socioeconomic status, course of epilepsy, as well as direct and indirect costs were recorded using validated patient questionnaires. We enrolled 101 patients in 2003 and 151 patients in 2008. In both cohorts, 76% of the patients suffered from focal epilepsy, and the majority was on antiepileptic drug (AED) polytherapy (mean AED number: 1.7 (2003), 1.8 (2008)). We calculated epilepsy-specific costs of € 2955 in 2003 and € 3532 in 2008 per 3 months per patient. Direct medical costs were mainly due to anticonvulsants in 2003 (59.4% of total direct costs, 34.0% in 2008) and to hospitalization in 2008 (46.9% of total direct costs, 27.7% in 2003). The proportion of enzyme-inducing anticonvulsants and 'old' AEDs decreased between 2003 and 2008. Indirect costs of € 1689 and € 1847 were mainly due to early retirement (48.4%; 46.0% of total indirect costs in 2003; 2008), unemployment (26.1%; 24.2%), and days off due to seizures (25.5%; 29.8%). This study showed a shift in distribution of direct cost components with increased hospital costs as well as a cost-neutral increase in the prescription of 'newer' AEDs. The amount and distribution of indirect cost components remained unchanged.

  9. Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds.

    Science.gov (United States)

    Streit, Anne K; Fan, Yuen Ngan; Masullo, Laura; Baines, Richard A

    2016-01-01

    Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure-like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds

  10. Synthesis and evaluation of 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives as potential anticonvulsants.

    Science.gov (United States)

    Madaiah, Malavalli; Prashanth, Maralekere K; Revanasiddappa, Hosakere D; Veeresh, Bantal

    2013-03-01

    New 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives 8-37 were synthesized and their pharmacological activities were determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. All the compounds were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test. Compounds 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the standard drug valproate. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drug. From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, that is, a lipophilic domain, a hydrophobic center, and a two-electron donor.

  11. Anticonvulsant Effects of Combined Treatment with Citicoline and Valproate on the Model of Acute Generalized Convulsions Induced by Pentylenetetrazole in Wistar Rats.

    Science.gov (United States)

    Karpova, M N; Kuznetsova, L V; Zin'kovskii, K A; Klishina, N V

    2016-02-01

    We studied anticonvulsant effects of combined treatment with citicoline, a nootropic substance with neuroregenerative and neuroprotective activities, and valproate, an antiepileptic agent widely used in the treatment of epilepsy, on the model of pentylenetetrazole-induced (75 mg/kg, intraperitoneally) acute generalized convulsions in male Wistar rats. Combined treatment with citicoline and valproate in minimum effective doses (70 and 300 mg/kg, respectively) potentiated the anticonvulsant properties of both agents.

  12. Intracerebroventricular administration of inosine is anticonvulsant against quinolinic acid-induced seizures in mice: an effect independent of benzodiazepine and adenosine receptors.

    Science.gov (United States)

    Ganzella, Marcelo; Faraco, Rafael Berger; Almeida, Roberto Farina; Fernandes, Vinícius Fornari; Souza, Diogo Onofre

    2011-12-01

    Inosine (INO) has an anticonvulsant effect against seizures induced by antagonists of GABAergic system. Quinolinic acid (QA) is an agonist NMDA receptors implicated in the neurobiology of seizures. In the present study, we investigated the anticonvulsant effect of intracerebroventricular (i.c.v.) INO administration against QA-induced seizures in adult mice. We also investigated whether the benzodiazepines (BZ) or adenosine (ADO) receptors were involved in the INO effects. Animals were pretreated with an i.c.v. injection of either vehicle or INO before an i.c.v. administration of 4 μl QA (36.8 nmol). All animals pretreated with vehicle followed by QA presented seizures. INO protected against QA-induced seizures in a time and dose dependent manner (up to 60% at 400 nmol, 5 min before QA injection). Diazepam (DZ) and ADO (i.c.v.) also exhibited anticonvulsant effect against QA induced seizures. Additionally, i.p. administration of either flumazenil, a BZ receptor antagonist, or caffeine, an ADO receptor antagonist, did not change the anticonvulsant potency of INO i.c.v. injection, but completely abolished the DZ and ADO anticonvulsant effects, respectively. In conclusion, this study demonstrated that INO exert anticonvulsant effect against hyperactivity of the glutamatergic system independently of BZ or ADO receptors activation.

  13. Quantitative structure activity relationship study of anticonvulsant activity of α_substituted acetamido-N-benzylacetamide derivatives

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    Usman Abdulfatai

    2016-12-01

    Full Text Available To develop the quantitative structure–activity relationship (QSAR for predicting the anticonvulsant activity of α_substituted acetamido-N-benzylacetamide derivatives. Density Functional Theory (B3LYP/6-31G* quantum chemical calculation method was used to find the optimized geometry of the studied molecules. Nine types of molecular descriptors were used to derive a quantitative relation between anticonvulsant activity and structural properties. The relevant molecular descriptors were selected by genetic algorithm approximation. The high value of the correlation coefficient, (R2 of 0.98, indicates that the model was satisfactory. The proposed model has good stability, robustness, and predictability on verifying with internal and external validation.

  14. Imidazole incorporated semicarbazone derivatives as a new class of anticonvulsants: design, synthesis and in-vivo screening.

    Science.gov (United States)

    Amir, Mohammad; Ali, Israr; Hassan, Mohd Zaheen

    2013-06-01

    A series of novel imidazole incorporated semicarbazones was synthesized using an appropriate synthetic route and characterized by spectral analysis (IR, 1H NMR, 13C NMR and Mass). The anticonvulsant activity of the synthesized compounds was determined using doses of 30, 100, and 300 mg kg-1 against maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Six compounds exhibited protection in both models and 2-(1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene)-N-p-tolylsemicarbazone emerged as the most active compound of the series without any neurotoxicity and significant CNS depressant effect. Liver enzyme estimations (SGOT, SGPT, Alkaline phosphatase) of the compound also showed no significant change in the enzymes levels. Moreover, it caused 80% elevation of γ-amino butyric acid (GABA) levels in the whole mice brain, thus indicating that it could be a promising candidate in designing of a potent anticonvulsant drug.

  15. Anticonvulsant and analgesic activities of crude extract and its fractions of the defensive secretion from the Mediterranean sponge, Spongia officinalis

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    Dellai Afef

    2012-04-01

    Full Text Available Abstract This study progresses in the direction of identifying component(s from the Mediterranean sponge, Spongia officinalis with anticonvulsant and analgesic activities. We investigated the efficacy of crude extract and its semi-purified fractions (F1-F3 of the defensive secretion from Spongia officinalis for their in vivo anticonvulsant activity using the pentylenetetrazole (PTZ seizure model and analgesic activity using the writhing test in mice. Among the series the crude extract exhibited interesting analgesic activity in a dose dependent manner. Similarly the fraction F2 showed a partial protection of mice from PTZ-induced seizure and interesting analgesic activity in a dose dependent manner. The purification and the determination of chemical structure(s of compound(s of this active fraction are under investigation.

  16. Evaluation of anticonvulsant effect of celecoxib, a selective cyclooxygenase-2 inhibitor in experimentally induced convulsions in albino rats

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    Mohammed Naseeruddin Nadeem; Maliha Maqdoom

    2016-01-01

    Background: Cyclooxygenase-2 (COX-2) exists as the inducible form of the cyclooxygenase enzyme, the levels of which are elevated in inflammatory conditions. COX-2 is located in regions of brain like hippocampus and cerebral cortex. When induced, COX-2 forms prostaglandin E2 (PGE2), which is responsible for CNS excitation, in turn leading to generation of seizures. COX-2 inhibitors by preventing the formation of PGE2 may serve as effective anticonvulsants. Since none of the anti-epileptics in ...

  17. Predictors of anti-convulsant treatment failure in children presenting with malaria and prolonged seizures in Kampala, Uganda

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    Byarugaba Justus

    2009-06-01

    Full Text Available Abstract Background In endemic areas, falciparum malaria remains the leading cause of seizures in children presenting to emergency departments. In addition, seizures in malaria have been shown to increase morbidity and mortality in these patients. The management of seizures in malaria is sometimes complicated by the refractory nature of these seizures to readily available anti-convulsants. The objective of this study was to determine predictors of anti-convulsant treatment failure and seizure recurrence after initial control among children with malaria. Methods In a previous study, the efficacy and safety of buccal midazolam was compared to that of rectal diazepam in the treatment of prolonged seizures in children aged three months to 12 years in Kampala, Uganda. For this study, predictive models were used to determine risk factors for anti-convulsant treatment failure and seizure recurrence among the 221 of these children with malaria. Results Using predictive models, focal seizures (OR 3.21; 95% CI 1.42–7.25, p = 0.005, cerebral malaria (OR 2.43; 95% CI 1.20–4.91, p = 0.01 and a blood sugar ≥200 mg/dl at presentation (OR 2.84; 95% CI 1.11–7.20, p = 0.02 were independent predictors of treatment failure (seizure persistence beyond 10 minutes or recurrence within one hour of treatment. Predictors of seizure recurrence included: 1 cerebral malaria (HR 3.32; 95% CI 1.94–5.66, p Conclusion Specific predictors, including cerebral malaria, can identify patients with malaria at risk of anti-convulsant treatment failure and seizure recurrence.

  18. Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.

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    Sawicka, Katarzyna M; Wawryniuk, Agnieszka; Zwolak, Agnieszka; Daniluk, Jadwiga; Szpringer, Monika; Florek-Luszczki, Magdalena; Drop, Bartlomiej; Zolkowska, Dorota; Luszczki, Jarogniew J

    2017-04-01

    Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.

  19. Binding interactions of convulsant and anticonvulsant gamma-butyrolactones and gamma-thiobutyrolactones with the picrotoxin receptor

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    Holland, K.D.; McKeon, A.C.; Covey, D.F.; Ferrendelli, J.A. (Washington Univ. School of Medicine, St. Louis, MO (USA))

    1990-08-01

    Alkyl-substituted gamma-butyrolactones (GBLs) and gamma-thiobutyrolactones (TBLs) are neuroactive chemicals. beta-Substituted compounds are convulsant, whereas alpha-alkyl substituted GBLs and TBLs are anticonvulsant. The structural similarities between beta-alkyl GBLs and the convulsant picrotoxinin suggested that alkyl substituted GBLs and TBLs act at the picrotoxin receptor. To test this hypothesis we examined the interactions of convulsant and anticonvulsant GBLs and TBLs with the picrotoxin, benzodiazepine and gamma-aminobutyric acid (GABA) binding sites of the GABA receptor complex. All of these convulsants and anticonvulsants studied competitively displaced 35S-t-butylbicyclophosphorothionate (35S-TBPS), a ligand that binds to the picrotoxin receptor. This inhibition of 35S-TBPS binding was not blocked by the GABA antagonist bicuculline methobromide. The convulsant GBLs and TBLs also partially inhibited (3H)muscimol binding to the GABA site and (3H)flunitrazepam binding to the benzodiazepine site, but they did so at concentrations substantially greater than those that inhibited 35S-TBPS binding. The anticonvulsant GBLs and TBLs had no effect on either (3H)muscimol or (3H)flunitrazepam binding. In contrast to the GBLs and TBLs, pentobarbital inhibited TBPS binding in a manner that was blocked by bicuculline methobromide, and it enhanced both (3H)flunitrazepam and (3H)muscimol binding. Both ethosuximide and tetramethylsuccinimide, neuroactive compounds structurally similar to GBLs, competitively displaced 35S-TBPS from the picrotoxin receptor and both compounds were weak inhibitors of (3H) muscimol binding. In addition, ethosuximide also partially diminished (3H)flunitrazepam binding. These data demonstrate that the site of action of alkyl-substituted GBLs and TBLs is different from that of GABA, barbiturates and benzodiazepines.

  20. Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted β-carotene nanoparticles

    Directory of Open Access Journals (Sweden)

    Yusuf M

    2012-08-01

    Full Text Available Mohammad Yusuf,1 Riaz A Khan,3 Maria Khan,2 Bahar Ahmed11Department of Pharmaceutical Chemistry, 2Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India; 3Department of Chemistry, Manav Rachna International University, National Capital Region, Aravali Hills, Faridabad, IndiaAbstract: β-Carotene has been established as a known free radical scavenger with chain-breaking antioxidant properties. It has been documented for the treatment of epileptic convulsions at a 200 mg/kg body weight dose. The reported pathogenesis for epileptic convulsions is oxidative stress. Hence, experimental epileptic convulsions via oxidative stress was induced in albino mice epileptic models (maximal electroshock seizure and pentylenetetrazole [PTZ]. A dose concentration equivalent to 2 mg/kg was efficaciously administered in the form of brain-targeted polysorbate-80-coated poly(d,l-lactide-co-glycolide nanoparticles. The nanoparticles were prepared by solvent evaporation technique and further characterized for their physical parameters, in-vitro release kinetics, and in-vivo brain release via various standard methods. Normal β-carotene nanoparticles (BCNP and polysorbate-80-coated β-carotene nanoparticles (P-80-BCNP of 169.8 ± 4.8 nm and 176.3 ± 3.2 nm in size, respectively, were formulated and characterized. Their zeta potential and polydispersity index were subsequently evaluated after 5 months of storage to confirm stability. In vivo activity results showed that a 2 mg unformulated β-carotene dose was ineffective as an anticonvulsant. However, salutary response was reported from BCNP at the same dose, as the hind limb duration decreased significantly in maximal electroshock seizure to 9.30 ± 0.86 seconds, which further decreased with polysorbate-80 coating to 2.10 ± 1.16 seconds as compared to normal control (15.8 ± 1.49 seconds and placebo control (16.50 ± 1.43 seconds. In the PTZ model, the duration of

  1. Synthesis and Pharmacological Evaluation of New 3,4-Dihydroisoquinolin Derivatives Containing Heterocycle as Potential Anticonvulsant Agents

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    Hong-Jian Zhang

    2016-11-01

    Full Text Available Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4a–t and 9a–e were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES test and pentylenetetrazole (PTZ-induced seizure test. All compounds were characterized by IR, 1H-NMR, 13C-NMR, and mass spectral data. Among them, 9-(exyloxy-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3(2H-one (9a showed significant anticonvulsant activity in MES tests with an ED50 value of 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9. It showed much higher anticonvulsant activity than that of valproate. It also demonstrated potent activity against PTZ-induced seizures. A docking study of compound 9a in the benzodiazepine (BZD-binding site of γ-aminobutyric acidA (GABAA receptor confirmed possible binding of compound 9a with the BZD receptors.

  2. Anticonvulsant and behavioral effects observed in mice following treatment with an ester derivative of ferulic acid: Isopentyl ferulate.

    Science.gov (United States)

    Machado, Keylla C; Oliveira, George Laylson S; Machado, Kátia C; Islam, Md Torequl; Junior, Antonio Luiz G; De Sousa, Damião P; Freitas, Rivelilson M

    2015-12-01

    The objective of this study was to evaluate the potential anticonvulsant effect of isopentyl ferulate, a new ester derived from ferulic acid in mice (Mus musculus) subjected to two models of induced seizures. According to the results obtained, the IF at doses of 25, 50 and 75 mg/kg (i.p.) showed protective effect against induced seizures by pilocarpine (400 mg/kg, i.p.) and pentylenetetrazole (70 mg/kg, i.p.). In the two animal models of seizures, the pretreatment of the IF (25, 50 and 75 mg/kg) with flumazenil blocked the anticonvulsant effect, suggesting that the mechanism of action of this ester derived of ferulic acid may be related to activity in the benzodiazepine-binding site of the GABAA receptor (γ-aminobutyric acid, type A). In addition to the anticonvulsant effect, behavioral changes as neurotoxicity indication were assessed by using the rota rod and open field tests. The results obtained showed that the IF (25, 50 and 75 mg/kg) does not induce significant changes in locomotor activity and motor coordination when compared with the control group, unlike the results presented by diazepam. Thus, these results demonstrate a new pharmacological knowledge of IF with potential application against epileptic seizures. However, further studies are needed to elucidate other neurobiological mechanisms underlying epilepsy.

  3. The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium.

    Science.gov (United States)

    Comai, Stefano; Tau, Michael; Pavlovic, Zoran; Gobbi, Gabriella

    2012-04-01

    Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

  4. Long-term ascorbic acid administration causes anticonvulsant activity during moderate and long-duration swimming exercise in experimental epilepsy.

    Science.gov (United States)

    Tutkun, Erkut; Arslan, Gokhan; Soslu, Recep; Ayyildiz, Mustafa; Agar, Erdal

    2015-01-01

    The benefits of regular exercise on brain health are undeniable. Long-term exercise increases the production of reactive oxygen species in brain. Therefore, athletes often consume antioxidant supplements to remedy exercise-related damage and fatigue during exercise. The aim of this study is to evaluate the role of ascorbic acid in the effects of different intensities of swimming exercise on the brain susceptibility to experimental epilepsy in rats. Ascorbic acid was administered intraperitoneally (ip) during three different swimming exercise programme for 90 days (15 min, 30 min, 90 min/day). The anticonvulsant activity regarding the frequency of epileptiform activity appeared in the 80 min after 500 units intracortical penicillin injection in 30 min and 90 min/day exercise groups. The administration of ascorbic acid (100 mg/kg, ip) did not alter the anticonvulsant properties seen in the in short-duration (15 min/day) swimming exercise group. The amplitude of epileptiform activity also became significant in the 110 and 120 min after penicillin injection in the moderate (30 min/day) and long duration (60 min/day) groups, respectively. The results of the present study provide electrophysiologic evidence that long-term administration of ascorbic acid causes anticonvulsant activities in the moderate and long-duration swimming exercise. Antioxidant supplementation such as ascorbic acid might be suggested for moderate and long-duration swimming exercise in epilepsy.

  5. Experimental allergic encephalomyelitis: peculiarities of pain-relieving therapy and place of anticonvulsants as analgetics

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    Nefyodov O.O.

    2015-11-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating disease affecting mainly young people of the working age (16-45 years and quickly leading to disability. Available data constitute that up to 80% of MS patients suffer from pain at different disease periods. Pain management and the analgesic drug choice in MS patients may be difficult. Anticonvulsant drugs possess an analgesic activity and are widely used in patients presenting painful neuropathic symptoms. Based on that, we aimed to investigate the nociceptive potential changes as well as the research-oriented behavior using the "open field" test in rat. An experimental animal equivalent of multiple sclerosis has been modeled, based on the methylprednisolone (M administration. Animals were also administered anticonvulsants (carbamazepine, topiramate, sodium volproat, pregabalin and gabapentin. The stu­dy showed advantages of gabapentin and pregabalin use in simulated disease treatment. This statement is based on the "open field" test results, where the motor-oriented rats’ behavior was evaluated. Administration of M+gabapentin and M+pregabalin showed positive dynamics of the motor activity: the number of squares crossed increased by 80.86% (p<0.05 and 81.73% (р<0.05 respectively. Maximum recovery of the research activity (peeking in "mink" was re­gis­tered in animals administered M+pregabalin: the increase rate was 300% (r<0.05 comparing with the 12th day of ex­periment. It was shown, that 5-days administration of M+gabapentin and M+pregabalin caused muscle tone impro­ve­ment by 190% (p<0.05 and 200% (p<0.05 respectively, comparing with animals with untreated multiple sclerosis. A sig­ni­fi­cant increase of analgesic activity of M+pregabalin and M+gabapentin combinations used together with me­thyl­pred­nisolone by 4.1 (p<0.05 and 3.6 (p<0.05 times was registered comparing with the initial methylprednisolone background.

  6. Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted β-carotene nanoparticles.

    Science.gov (United States)

    Yusuf, Mohammad; Khan, Riaz A; Khan, Maria; Ahmed, Bahar

    2012-01-01

    β-Carotene has been established as a known free radical scavenger with chain-breaking antioxidant properties. It has been documented for the treatment of epileptic convulsions at a 200 mg/kg body weight dose. The reported pathogenesis for epileptic convulsions is oxidative stress. Hence, experimental epileptic convulsions via oxidative stress was induced in albino mice epileptic models (maximal electroshock seizure and pentylenetetrazole [PTZ]). A dose concentration equivalent to 2 mg/kg was efficaciously administered in the form of brain-targeted polysorbate-80-coated poly(d,l-lactide-co-glycolide) nanoparticles. The nanoparticles were prepared by solvent evaporation technique and further characterized for their physical parameters, in-vitro release kinetics, and in-vivo brain release via various standard methods. Normal β-carotene nanoparticles (BCNP) and polysorbate-80-coated β-carotene nanoparticles (P-80-BCNP) of 169.8 ± 4.8 nm and 176.3 ± 3.2 nm in size, respectively, were formulated and characterized. Their zeta potential and polydispersity index were subsequently evaluated after 5 months of storage to confirm stability. In vivo activity results showed that a 2 mg unformulated β-carotene dose was ineffective as an anticonvulsant. However, salutary response was reported from BCNP at the same dose, as the hind limb duration decreased significantly in maximal electroshock seizure to 9.30 ± 0.86 seconds, which further decreased with polysorbate-80 coating to 2.10 ± 1.16 seconds as compared to normal control (15.8 ± 1.49 seconds) and placebo control (16.50 ± 1.43 seconds). In the PTZ model, the duration of general tonic-clonic seizures reduced significantly to 2.90 ± 0.98 seconds by the use of BCNP and was further reduced on P-80-BCNP to 1.20 ± 0.20 seconds as compared to PTZ control and PTZ-placebo control (8.09 ± 0.26 seconds). General tonic-clonic seizures latency was increased significantly to 191.0 ± 9.80 seconds in BCNP and was further

  7. Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

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    Del-Bel E.A.

    1997-01-01

    Full Text Available The effect of acute (120 mg/kg and chronic (25 mg/kg, twice a day, for 4 days intraperitonial injection of the nitric oxide (NO synthase (NOS inhibitor NG-nitro-L-arginine (L-NOARG was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ and by sound stimulation of audiogenic seizure-resistant (R and audiogenic seizure-susceptible (S rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg and protected against PTZ-induced tonic seizures (80 mg/kg. The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure

  8. Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents

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    Da-Chuan Liu

    2016-02-01

    Full Text Available New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES, subcutaneous pentylenetetrazole (scPTZ, and rotarod neurotoxicity (TOX tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-ylthio-N-(6-((3-fluorobenzyl oxybenzo[d]thiazol-2-ylacetamide (5i and 2-((1H-1,2,4-triazol-3-ylthio-N-(6-((4-fluorobenzyloxy benzo[d] thiazol-2-ylacetmide (5j were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study.

  9. Fluoxetine enhances the anticonvulsant effects of conventional antiepileptic drugs in maximal electroshock seizures in mice.

    Science.gov (United States)

    Borowicz, Kinga K; Stepień, Karolina; Czuczwar, Stanisław J

    2006-01-01

    The present study was designed to investigate the effects of fluoxetine (FXT), a selective serotonin reuptake inhibitor, on the effect of antiepileptic drugs (AEDs) in the maximal electroshock seizure (MES) model in mice. FXT at the doses of 25, 20 and 15 mg/kg significantly increased the electroconvulsive threshold. The antidepressant applied at the lower doses (10, 5 and 2.5 mg/kg) did not influence the threshold. Moreover, FXT (at the highest subprotective dose of 10 mg/kg) increased the anticonvulsive potential of carbamazepine (CBZ), diphenylhydantoin (DPH), valproate (VPA) and phenobarbital (PB), producing a dose-related decrease in their ED50 values against MES. Nevertheless, pharmacokinetic events may be involved in the interaction between FXT and PB or CBZ, since the antidepressant raised the total brain concentration of the two antiepileptics. FXT in combination with AEDs did not influence the motor performance in the chimney test and long-term memory. In conclusion, the data suggest that FXT modulates seizure processes in the brain and may be advantageous in the treatment of epilepsy in depressed patients, improving the seizure control in epilepsy.

  10. Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants.

    Science.gov (United States)

    Nikalje, Anna P; Ansari, Altamash; Bari, Sanjay; Ugale, Vinod

    2015-06-01

    A series of 2-(substituted-phenyl)-3-(2-oxoindolin-3-ylidene)amino)-thiazolidin-4-one derivatives were designed and synthesized under microwave irradiation, using an eco-friendly, efficient, microwave-assisted synthetic protocol that involves cyclocondensation of 3-substituted benzylidine-hydrazono-indolin-2-one 3a-j with thioglycolic acid in dimethyl formamide (DMF) as solvent and anhydrous zinc chloride as a catalyst, keeping in view the structural requirement of the pharmacophore. The intermediate compounds 3a-j were obtained by condensation of the hydrazone of indoline-2,3-dione with aromatic aldehydes. The synthesized derivatives were evaluated for CNS depressant activity and anticonvulsant activity in mice using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) induced seizure tests. All the derivatives showed good CNS depressant activity and showed protection in the MES test, indicative of their ability to inhibit the seizure spread. A histopathological study was performed to evaluate liver toxicity caused by the synthesized compounds. The compounds were nontoxic. A computational study was performed, in which log P values were calculated experimentally. Virtual screening was performed by molecular docking of the designed compounds into the ATP binding sites of the NMDA and AMPA receptors, to predict if these compounds have analogous binding modes.

  11. Anticonvulsant actions of anticholinergic drugs in soman poisoning. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Capacio, B.R.; Shih, T.M.

    1991-12-31

    The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds, aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 micro mol per kilogram for scopolamine HBr, biperiden, trihexyphenidy, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order by potency for inhibition of hypersecretions among these compounds was observed.

  12. Clorazepate in dogs: tolerance to the anticonvulsant effect and signs of physical dependence.

    Science.gov (United States)

    Scherkl, R; Kurudi, D; Frey, H H

    1989-01-01

    Dogs were treated with clorazepate, which is known to be completely metabolized to desmethyldiazepam. 2 mg/kg t.i.d. were given orally for 5-6 weeks, a dose regimen providing plasma concentrations of desmethyldiazepam in the range known to be therapeutic in man. The rate of development of tolerance to the anticonvulsant effect was followed by weekly determinations of the convulsive threshold for pentetrazole before, during and after cessation of treatment. The development of tolerance was not as clear and pronounced as that found after treatment with diazepam and clonazepam in earlier studies with dogs. The seizure threshold was elevated by a factor of 1.2-3.5 during the first 2 weeks of treatment; during the following weeks, tolerance developed in only 2 out of 6 dogs (decline of the pentetrazole threshold in spite of rising or unchanged plasma concentrations). 36 h after withdrawal of clorazepate, the convulsive threshold had fallen below the control values in all dogs, but 1 week later it had returned to the control level. One day after cessation of treatment, 2 out of 6 dogs showed withdrawal seizures, which, in 1 case, were lethal. This shows that severe withdrawal symptoms, even lethal seizures, may appear after abrupt discontinuation of chronic clorazepate treatment, in spite of the relatively low tolerance liability of clorazepate.

  13. The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome.

    Science.gov (United States)

    Watson, W P; Robinson, E; Little, H J

    1997-10-01

    The effects of the anticonvulsant, gabapentin, were investigated, in mice, on the withdrawal convulsive behaviour and anxiety-related behaviour that are produced by cessation of prolonged intake of ethanol. When given at 50 or 100 mg/kg, this compound decreased the rise in handling-induced hyperexcitability which occurs during the withdrawal period; the effects were most pronounced for the first 4 hr after administration. Gabapentin also decreased the convulsive response to an audiogenic stimulus during the withdrawal period. The elevated plus-maze, with both traditional and ethological indices of activity was used as a test of anxiety-related behaviour after cessation of chronic ethanol treatment. Gabapentin, at 50 and 100 mg/kg, was found to decrease some, although not all, of the signs of withdrawal-induced anxiety. At doses up to and including 200 mg/kg, gabapentin had no effect on motor co-ordination or spontaneous locomotor activity in control animals. The results demonstrated that gabapentin has a selective action in decreasing both convulsive and anxiety-related aspects of withdrawal behaviour after chronic ethanol treatment. It is possible that further studies with this compound may shed further light on the mechanisms involved in the withdrawal syndrome.

  14. Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis, molecular docking and anticonvulsant studies.

    Science.gov (United States)

    Karataş, Mert Olgun; Uslu, Harun; Sarı, Suat; Alagöz, Mehmet Abdullah; Karakurt, Arzu; Alıcı, Bülent; Bilen, Cigdem; Yavuz, Emre; Gencer, Nahit; Arslan, Oktay

    2016-10-01

    Among many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties. In this study, we prepared fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives and evaluated their hCA inhibitory activities and along with fourteen previously synthesized derivatives we scanned their anticonvulsant effects. As all compounds inhibited purified hCA isoforms I and II, some of them also proved protective against Maximal electroshock seizure (MES) and ScMet induced seizures in mice. Molecular docking studies with selected coumarin derivatives have revealed that these compounds bind to the active pocket of the enzyme in a similar fashion to that previously described for coumarin derivatives.

  15. A novel anticonvulsant modulates voltage-gated sodium channel inactivation and prevents kindling-induced seizures.

    Science.gov (United States)

    Ashraf, Muhammad N; Gavrilovici, Cezar; Shah, Syed U Ali; Shaheen, Farzana; Choudhary, Muhammad I; Rahman, Atta-ur; Fahnestock, Margaret; Simjee, Shabana U; Poulter, Michael O

    2013-09-01

    Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices isolated from controls and rats with experimental epilepsy(kindling model). Quantitative transcription polymerase chain reaction (qRT-PCR) (QPCR) assessed brain-derived neurotrophic factor (BDNF) mRNA expression in kindled rats, and kindled rats treated with ISOX. ISOX suppressed sodium current (I(Na)) showing an IC50 value of 185 nM in cultured neurons. ISOX significantly slowed the recovery from inactivation (ISOX τ = 18.7 ms; Control τ = 9.4 ms; p kindled cortical neurons, the IC50 for sodium current block was identical to that found in cultured neurons. ISOX prevented kindled stage 5 seizures and decreased the enhanced BDNF mRNA expression that is normally associated with kindling (p kindling is likely a secondary outcome that nevertheless would suppress epileptogenesis. These data show a new class of anti-seizure compound that inhibits sodium channel function and prevents the development of epileptic seizures.

  16. Intoxicaciones medicamentosas (II: Analgésicos y anticonvulsivantes Acute pharmacologic poisoning (II: Analgesics and anticonvulsants

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    P. Munné

    2003-01-01

    Full Text Available En este segundo capítulo sobre Intoxicaciones Medicamentosas Agudas abordamos dos grupos de sustancias de enorme trascendencia desde el punto de vista de su uso y morbimortalidad. Dentro del grupo de los anagésicos-antiinflamatorios desarrollamos el paracetamol y los salicilatos, de enorme disponibilidad para la población. En cuanto a los anticonvulsivantes, aunque están poco implicados en el conjunto de las intoxicaciones medicamentosas agudas, sus efectos pueden ser graves. Nos ceñimos a cuatro fármacos: ácido valproico, fenobarbital, carbamacepina, y fenitoína. Finalmente dedicamos un apartado a la isoniacida, fármaco que, con el rebrote de la tuberculosis, presenta interés toxicológico.In this second chapter on Acute Drugs Poisoning we deal with two groups of substances of great transcendence from the point of view of their use and morbidity/mortality. Within the group of analgesic-anti-inflammatory drugs we consider paracetamol and the salicylates, which are easily available to the population. With respect to the anticonvulsants, although they are barely involved in the ensemble of acute drug poisonings, their effects can be serious. We concentrate on four drugs: valproic acid, phenobarbitol, carbamacepine, and phenytoin. Finally, a section is dedicated to isoniazid, a drug that, with the renewed incidence of tuberculosis, is of toxicological interest.

  17. Antipyretic and anticonvulsant activity of n-hexane fraction of Viola betonicifolia

    Institute of Scientific and Technical Information of China (English)

    Naveed Muhammad; Muhammad Saeed; Haroon Khan; Naila Raziq; Syed Muhammad Ashhad Halimi

    2013-01-01

    Objective: To investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia (V. betonicifolia). Methods: The antipyretic effect was scrutinized using brewer’s yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice. Results: N-hexane fraction of V. betonicifolia demonstrated highly significant antipyretic activity during various assessment times (1-5 h) when challenged in yeast induced pyrexia test. The effect was in a dose dependent manner with maximum attenuation (82.50%) observed at 300 mg/kg i.p. When tested in pentylenetetrazol induced convulsion test, the 1st stage (Ear and facial twitching) and 2nd stage (Convulsive wave through the body) was 100% protected during 24 h at all the test doses (300, 400 and 500 mg/kg i.p.), while the latency time of remaining stages was significantly increased. The maximum effect was observed by n-hexane fraction of V. betonicifolia at 400 and 500 mg/kg i.p., as the latency time for generalized clonic-tonic seizure (5th stage) was increased up to 25.34 min. However, n-hexane fraction of V. betonicifolia had no protection in strychnine induced convulsion test. Conclusions:In conclusion, phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders.

  18. Antipyretic and anticonvulsant activity of n-hexane fraction of viola betonicifolia

    Institute of Scientific and Technical Information of China (English)

    Naveed; Muhammad; Muhammad; Saeed; Haroon; Khan; Naila; Raziq; Syed; Muhammad; Ashhad; Halimi

    2013-01-01

    Objective:To investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia(V.betonicifolia).Methods:The antipyretic effect was scrutinized using brewer’s yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice.Results:N-hexane fraction of V.betonicifolia demonstrated highly significant antipyretic activity during various assessment times(1-5 h)when challenged in yeast induced pyrexia test.The effect was in a dose dependent manner with maximum attenuation(82.50%)observed at 300 mg/kg i.p.When tested in pentylenetetrazol induced convulsion test,the 1st stage(Ear and facial twitching)and 2nd stage(Convulsive wave through the body)was 100%protected during 24 h at all the test doses(300,400 and 500 mg/kg i.p.),while the latency time of remaining stages was significantly increased.The maximum effect was observed by n-hexane fraction of V.betonicifolia at 400 and 500 mg/kg i.p.,as the latency time for generalized clonic-tonic seizure(5th stage)was increased up to 25.34 min.However,n-hexane fraction of V.betonicifolia had no protection in strychnine induced convulsion test.Conclusions:In conclusion,phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders.

  19. A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function.

    Science.gov (United States)

    Tietz, E I; Rosenberg, H C; Chiu, T H

    1989-01-01

    Studies suggest that the 1,5-benzodiazepine clobazam possesses a favorable anticonvulsant profile due to its minimal neurotoxicity. The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone. All drugs produced a significant, dose-dependent decrease in the duration of both behavioral and electrographic kindled seizure measures. Forelimb clonus suppression was the most sensitive measure of anticonvulsant drug effect. The order of potency for all effects was clonazepam greater than diazepam greater than clobazam. ED50s for the benzodiazepines' effects on motor impairment were compared to their ability to protect rats from forelimb clonus. Different spectrums of action for the various benzodiazepines were found depending on the comparison measure. Clonazepam had the most favorable ratio of potency for anticonvulsant vs. motor impairment activity when ataxia rating was the comparison measure. Diazepam had the most advantageous profile when the more sensitive screen test was used for comparison. Clobazam was not found to have a superior spectrum of action when compared across these measures. The results emphasize the importance of dose-response analyses and the consideration of behavioral measures used to assess beneficial and adverse effects of anticonvulsants.

  20. Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol.

    Science.gov (United States)

    Sadek, Bassem; Shehab, Safa; Więcek, Małgorzata; Subramanian, Dhanasekaran; Shafiullah, Mohamed; Kieć-Kononowicz, Katarzyna; Adem, Abdu

    2013-09-01

    Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H3R ligands 1-13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H3R ligand among 1-13, was significantly higher (P histamine (RAMH) (10mg/kg), or with the CNS penetrant H1R antagonist Pyrilamine (PYR) (10mg/kg). In addition, subeffective dose of H3R ligand 4 (5mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H3R ligand 4 (10mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H3R ligands 1-13 may be of future therapeutic value in epilepsy.

  1. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders.

    Science.gov (United States)

    Hammond, Christopher J; Niciu, Mark J; Drew, Shannon; Arias, Albert J

    2015-04-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

  2. The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice.

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    Bingjin Li

    Full Text Available Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4 of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.

  3. Activation of adenosine receptor potentiates the anticonvulsant effect of phenytoin against amygdala kindled seizures.

    Science.gov (United States)

    Sun, Zhen; Zhong, Xiao-Ling; Zong, Yu; Wu, Zhong-Chen; Zhang, Qun; Yu, Jin-Tai; Tan, Lan

    2015-01-01

    Drug resistance in epilepsy is considered as a complicated and multifactorial problem. Poor penetration of antiepileptic drugs (AEDs) across blood-brain barrier (BBB) into the brain, which results in insufficient level of the drugs at the targeted brain region, has been discussed as one mechanism contributing to pharmacoresistance of epilepsies. Therefore, modulating permeability of BBB is the effective treatment strategy since it facilitates the entry of AEDs into the central nervous system (CNS). Recently, signaling through receptors for the adenosine has been identified as a potent modulator of BBB permeability. This paper aimed to investigate the effects of auxiliary application of adenosine receptor (AR) agonist on amygdala-kindled seizures in adult male Wistar rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, rats were randomly divided into three groups: control, phenytoin, and phenytoin (PHT)+5'-N-ethylcarboxamidoadenosine (NECA) groups. NECA (0.08 mg/kg, i.v.) was applied to the PHT+NECA group after the administration of PHT (75 mg/kg, i.p. on the first day; 50mg/kg, i.p. on the following 9 days). Intravenous infusion of NECA resulted in a significant increase in brain PHT levels as compared with the PHT treatment alone. On the other hand, the auxiliary application of NECA dramatically decreased the frequency of generalized seizures and seizure stage, shortened duration of afterdischarge and generalized seizures, as well as the elevated the afterdischarge threshold and generalized seizures threshold. Our study demonstrated that auxiliary application of AR agonist enhanced brain antiepileptic drug levels and strengthened the anticonvulsant properties of PHT against amygdala kindled seizures.

  4. Effects of the anticonvulsant lacosamide compared to valproate and lamotrigine on cocaine-enhanced reward in rats.

    Science.gov (United States)

    Béguin, Cécile; Potter, David N; Carlezon, William A; Stöhr, Thomas; Cohen, Bruce M

    2012-10-15

    Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in producing the mood-stabilizing effects of anticonvulsant drugs. We tested whether lacosamide would have effects similar to or different from valproate and lamotrigine in a model of reward and elevated mood. The intracranial self-stimulation (ICSS) test is sensitive to the function of brain reward systems. Changes in ICSS may model aspects of disorders characterized by abnormalities of reward and motivation. Cocaine elevates mood, and reduction of cocaine-induced facilitation of ICSS has been used to predict antimanic-like or mood stabilizing effects of drugs. We tested lacosamide, lamotrigine, and valproate in the rat ICSS test alone or in the presence of cocaine. A high dose of lacosamide (30 mg/kg) significantly elevated ICSS thresholds, indicating that it reduced the rewarding impact of medial forebrain bundle stimulation. Lower doses (3-10 mg/kg) did not alter ICSS, but blocked the cocaine-induced lowering of ICSS thresholds. The highest doses of valproate (300 mg/kg) and lamotrigine (30 mg/kg) also elevated ICSS thresholds, and only these high doses significantly lowered cocaine-induced effects. Of the drugs tested, only lacosamide significantly attenuated the reward-facilitating effects of cocaine at doses that had no effects on ICSS response in the absence of cocaine. Abnormalities of mood and reward are common in psychiatric disorders, and these results suggest that lacosamide deserves further study in models of these disorders.

  5. Anticonvulsant and antioxidant effects of Tilia americana var. mexicana and flavonoids constituents in the pentylenetetrazole-induced seizures.

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; González-Trujano, María Eva; Aguirre-Hernández, Eva; Ruíz-García, Matilde; Sampieri, Aristides; Coballase-Urrutia, Elvia; Carmona-Aparicio, Liliana

    2014-01-01

    Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p.) and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg), rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg), and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg). In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids.

  6. Anticonvulsant and Antioxidant Effects of Tilia americana var. mexicana and Flavonoids Constituents in the Pentylenetetrazole-Induced Seizures

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2014-01-01

    Full Text Available Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p. and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg, rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg, and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg. In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids.

  7. Anticonvulsant and Antioxidant Effects of Tilia americana var. mexicana and Flavonoids Constituents in the Pentylenetetrazole-Induced Seizures

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; González-Trujano, María Eva; Aguirre-Hernández, Eva; Ruíz-García, Matilde; Sampieri, Aristides; Coballase-Urrutia, Elvia; Carmona-Aparicio, Liliana

    2014-01-01

    Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p.) and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg), rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg), and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg). In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids. PMID:25197430

  8. Synthesis and Some Reactions of 1-aryl-4-acetyl-5-methyl-1,2,3-triazole Derivatives with Anticonvulsant Activity.

    Science.gov (United States)

    Nassar, Ekhlass M; Abdelrazek, Fathy M; Ayyad, Rezk R; El-Farargy, Ahmed F

    2016-01-01

    The triazoles 3a-d underwent condensation reactions with 4-(piperidin-1-yl)-benzaldehyde to afford the chalcones 5a-d. Chalcone derivatives 5a-d were reacted with 2,3-diaminomaleonitrile, thiourea and hydrazine hydrate to afford the novel diazepine-dicarbonitrile derivatives 7a-d, the pyrimidine-2-thiol derivatives 9a-d and hydrazino-pyrimidines 10a-d respectively. Structures of the prepared compounds were elucidated by physical and spectral data like FT-IR, (1)H NMR, (13)C NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their anticonvulsant activity and SAR.

  9. Synthesis and anticonvulsant activity of some potent 5,6-bis aryl 1,2,4-triazines

    Institute of Scientific and Technical Information of China (English)

    MALLIKARJUNA B.P.; SURESH KUMAR G.V.; SASTRY B.S.; NAGARAJ; MANOHARA K.P.

    2007-01-01

    In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a~5f were synthesized by condensation of various benzils 4a~4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies.Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.

  10. Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

    Science.gov (United States)

    El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl, K.; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M.

    2017-02-01

    In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

  11. Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus.

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; Sombati, Sompong; Falenski, Katherine W; Martin, Billy R; DeLorenzo, Robert J

    2006-06-01

    Cannabinoids have been shown to have anticonvulsant properties, but no studies have evaluated the effects of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy (AE) and status epilepticus (SE). This study investigated the anticonvulsant properties of the cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolol[1,2,3 de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone (WIN 55,212-2) in primary hippocampal neuronal culture models of both AE and SE. WIN 55,212-2 produced dose-dependent anticonvulsant effects against both spontaneous recurrent epileptiform discharges (SRED) (EC50 = 0.85 microM) and SE (EC50 = 1.51 microM), with total suppression of seizure activity at 3 microM and of SE activity at 5 microM. The anticonvulsant properties of WIN 55,212-2 in these preparations were both stereospecific and blocked by the cannabinoid type-1 (CB1) receptor antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A; 1 microM), showing a CB1 receptor-dependent pathway. The inhibitory effect of WIN 55,212-2 against low Mg2+-induced SE is the first observation in this model of total suppression of SE by a selective pharmacological agent. The clinically used anticonvulsants phenytoin and phenobarbital were not able to abolish low Mg2+-induced SE at concentrations up to 150 microM. The results from this study show CB1 receptor-mediated anticonvulsant effects of the cannabimimetic WIN 55,212-2 against both SRED and low Mg2+-induced SE in primary hippocampal neuronal cultures and show that these in vitro models of AE and SE may represent powerful tools to investigate the molecular mechanisms mediating the effects of cannabinoids on neuronal excitability.

  12. Evaluation of Anti-Convulsant Activity of Methanolic Extract of Seeds of Cassia Fistula against Pentylenetetrazole induced convulsions in mice

    Directory of Open Access Journals (Sweden)

    Nilesh P. Sawadadkar

    2014-06-01

    Full Text Available Cassia Fistula is a popular Indian herb which is used as tonic, laxative, anti-pyretic, astringent, febrifuge, strong purgative etc. The aim of present study was to evaluate anticonvulsant activity of methanolic extract of seeds of Cassia Fistula against pentylenetetrazol (PTZ induced convulsions in mice. All the animals were divided into four groups of six mice each and were injected PTZ (60mg/kg intraperitonially Group I was served as toxic control, Group II was pretreated with  Gabapentin (200mg/kg P.O.. Group III was pretreated with  methanolic extract of seeds of Cassia Fistula (100 mg/kg P.O. for 7 days. Group IV was pretreated with  methanolic extract of seeds of Cassia Fistula (200mg/kg P.O. for 7 days.The result shows that methanolic extract of seeds of Cassia Fistula significantly reduced duration of clonic convulsions and also delayed the onset of convulsions induced by pentylenetetrazol. The result was expressed as mean ± SEM and were statistically analyzed by one way ANOVA. It is concluded that methanolic extract of seeds of Cassia Fistula can show anticonvulsant activity against pentylenetetrazol induced convulsions in mice.

  13. Synthesis, characterization and screening for antidepressant and anticonvulsant activity of 4,5-dihydropyrazole bearing indole derivatives

    Directory of Open Access Journals (Sweden)

    Pravin O. Patil

    2016-07-01

    Full Text Available In the present study, a series of new substituted 5-(1H-Indol-3-yl-3-(phenyl-4,5-dihydropyrazoline derivatives (2a–m have been synthesized with good yield by microwave assisted synthesis. The compounds synthesized were screened for antidepressant and anticonvulsant potentialities in mice by a forced swim test and subcutaneous pentylenetetrazole (scPTZ test, respectively. Neuro-toxicities were determined by rotarod test in albino mice. The structures of all new compounds were confirmed by IR, 1H NMR, mass spectral data, and microanalyses. The results revealed that compounds 2b, 2e and 2k were found to be potent antidepressant molecules of the series, at 20 mg/kg dose level when compared with the reference drugs imipramine and fluoxetine. Whereas, compounds 2c and 2d were found to be potent anticonvulsant molecules of this series, when compared with the reference drug diazepam. None of the synthesized compounds showed neurotoxicity.

  14. Comparing the anticonvulsant effects of low frequency stimulation of different brain sites on the amygdala kindling acquisition in rats.

    Science.gov (United States)

    Esmaeilpour, Khadijeh; Masoumi-Ardakani, Yaser; Sheibani, Vahid; Shojaei, Amir; Harandi, Shaahin; Mirnajafi-Zadeh, Javad

    2013-01-01

    Low frequency stimulation (LFS) is a potential alternative therapy for epilepsy. However, it seems that the anticonvulsant effects of LFS depend on its target sites in the brain. Thus, the present study was designed to compare the anticonvulsant effects of LFS administered to amygdala, piriform cortex and substantia nigra on amygdala kindling acquisition. In control group, rats were kindled in a chronic manner (one stimulation per 24 h). In other experimental groups, animals received low-frequency stimulation (8 packages at 100 s intervals, each package contained 200 monophasic square-wave pulses, 0.1 ms pulse duration at 1 Hz andAD threshold intensity) in amygdala, piriform cortex or substantia nigra 60 seconds after the kindling stimulation, the AD duration and daily seizure stages were recorded. The obtained results showed that administration of LFS in all three regions reduced electrical and behavioral parameters of the kindling procedure. However LFS has a stronger inhibitory effect on kindling development when applied in substantia nigra compared to the amygdala and piriform cortex which reinforce the view that the substantia nigra mediates a crucial role in amygdala-kindled seizures. LFS had also greater inhibitory effects when applied to the amygdala compared to piriform cortex. Thus, it may be suggested that antiepileptogenic effect of LFS depends on its target site and different brain areas exert different inhibitory effects on kindling acquisition according to the seizure focus.

  15. Anticonvulsant Effect of Ferula Assa-Foetida Oleo Gum Resin on Chemical and Amygdala-Kindled Rats

    Science.gov (United States)

    Bagheri, Seyyed Majid; Rezvani, Mohamad Ebrahim; Vahidi, Ali Reza; Esmaili, Mansur

    2014-01-01

    Background: In Iranian traditional medicine, Ferula assa-foetida oleo gum resin (asafoetida) have been used as anti-convulsant agents. Aims: This study was designed to evaluate the anti-convulsant effect of asafoetida on chemical and amygdala -kindled rats. Materials and Methods: In chemical model, rats received orally asafoetida at dose of 50 and 100 mg/kg 90 minutes prior to Pentylenetetrazol injection in dose of 35 mg/kg intraperitoneally (i.p.) and control group received normal saline. Convulsive behavior was recorded for 30 minutes. For amygdala kindle model, bipolar stimulating and monopolar recording electrodes were implanted stereotaxically. After kindling, the effect of asafoetida (50 and 100mg/kg) on after discharge duration, duration of stage 5 seizure and latency to the onset of bilateral forelimb clonuses was measured. Results: Pretreatment animals with asafoetida significantly reduced the mean seizure stage during the 20 kindling injection of Pentylenetetrazol. Seizure parameters in amigdala kindle model improved in treatment animals at both dose 50 and 100 mg/kg. The number of stimulations in stage 3, 4, and 5 in asafoetida-treated rats at both doses significantly increased. Conclusions: These results showed that asafoetida could prevent seizure in both chemical and electrical kindling model and this effect may partially be related to the terpenoids compounds. PMID:25210675

  16. Anticonvulsant effect of ferula assa-foetida oleo gum resin on chemical and amygdala-kindled rats

    Directory of Open Access Journals (Sweden)

    Seyyed Majid Bagheri

    2014-01-01

    Full Text Available Background: In Iranian traditional medicine, Ferula assa-foetida oleo gum resin (asafoetida have been used as anti-convulsant agents. Aims: This study was designed to evaluate the anti-convulsant effect of asafoetida on chemical and amygdala -kindled rats. Materials and Methods: In chemical model, rats received orally asafoetida at dose of 50 and 100 mg/kg 90 minutes prior to Pentylenetetrazol injection in dose of 35 mg/kg intraperitoneally (i.p. and control group received normal saline. Convulsive behavior was recorded for 30 minutes. For amygdala kindle model, bipolar stimulating and monopolar recording electrodes were implanted stereotaxically. After kindling, the effect of asafoetida (50 and 100mg/kg on after discharge duration, duration of stage 5 seizure and latency to the onset of bilateral forelimb clonuses was measured. Results: Pretreatment animals with asafoetida significantly reduced the mean seizure stage during the 20 kindling injection of Pentylenetetrazol. Seizure parameters in amigdala kindle model improved in treatment animals at both dose 50 and 100 mg/kg. The number of stimulations in stage 3, 4, and 5 in asafoetida-treated rats at both doses significantly increased. Conclusions: These results showed that asafoetida could prevent seizure in both chemical and electrical kindling model and this effect may partially be related to the terpenoids compounds.

  17. Detection of teratogens in human serum using rat embryo culture: cancer and epilepsy treatments. [Detecting teratogenicity of anticonvulsant and antineoplastic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Chatot, C. L.

    1979-01-01

    Growth (protein and DNA contents) of headfold stage rat embryos cultured for 48 hrs on human serum was enhanced by glucose supplementation. Embryo growth varied with the source of the serum. Sera from 3 of the 19 control subjects produced abnormal embryos. Sera from 5 subjects undergoing cancer chemotherapy and 6 subjects receiving anticonvulsants were either lethal or teratogenic to cultured rat embryos.

  18. Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated from leaves of Mangifera indica.

    Science.gov (United States)

    Viswanatha, G L; Mohan, C G; Shylaja, H; Yuvaraj, H C; Sunil, V

    2013-07-01

    The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

  19. Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

    Science.gov (United States)

    Gadow, Kenneth D.

    As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

  20. A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben

    Science.gov (United States)

    Talevi, Alan; Bellera, Carolina L.; Castro, Eduardo A.; Bruno-Blanch, Luis E.

    2007-09-01

    A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.

  1. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Theard, M A; Pelligrino, D A;

    1994-01-01

    ) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

  2. Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy.

    Science.gov (United States)

    Shao, Hui; Yang, Yang; Mi, Ze; Zhu, Guang-Xi; Qi, Ai-Ping; Ji, Wei-Gang; Zhu, Zhi-Ru

    2016-11-19

    Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition.

  3. A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.

    Science.gov (United States)

    Talevi, Alan; Bellera, Carolina L; Castro, Eduardo A; Bruno-Blanch, Luis E

    2007-09-01

    A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.

  4. Anticonvulsant effect of time-restricted feeding in a pilocarpine-induced seizure model: Metabolic and epigenetic implications.

    Directory of Open Access Journals (Sweden)

    Jorge eLandgrave-Gómez

    2016-01-01

    Full Text Available A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine-induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL and a second group underwent a time-restricted feeding (TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE, and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 hours after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (β-HB concentration, an endogenous inhibitor of histone deacetylases (HDACs. Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3 in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the

  5. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety.

  6. Uso potencial dos anticonvulsivantes no tratamento ambulatorial da dependência de álcool Potential use of the anticonvulsants in the outpatient treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Luís André Castro

    2006-01-01

    Full Text Available Atualmente três medicações (dissulfiram, naltrexona e acamprosato são aprovadas pela Food and Drug Administration (FDA para tratar a dependência de álcool. As drogas anticonvulsivantes clássicas são raramente empregadas como alternativa por causa dos seus efeitos colaterais, mas a sua última geração pode ser útil. Os anticonvulsivantes podem ser uma alternativa aos benzodiazepínicos (BZD e a outros tratamentos farmacológicos na prevenção de complicações na desintoxicação por apresentarem ausência de propriedades aditivas e um melhor perfil de efeitos adversos do que os anticonvulsivantes clássicos. Anticonvulsivantes como carbamazepina, ácido valpróico, gabapentina e topiramato demonstraram-se excelentes tratamentos para síndrome de abstinência do álcool e prevenção de recaídas. Embora nenhum desses agentes tenha sido aprovado pela FDA, existe uma crescente evidência na literatura que apóia o seu uso.Currently three medications (disulfiram, naltrexone and acamprosate are approved by the FDA to treat alcohol dependence by the FDA. The classical anticonvulsive drugs are rarely employed as an alternative because of their side effects, but the latest generation of anticonvulsants could be useful. The anticonvulsants can be a alternative to BZD and other pharmacological treatments in the prevention of complications during the detoxification therapy, because of the absence of addictive properties and a better adverse effects profile than classical anticonvulsant drugs. Anticonvulsants such as carbamazepine, valproic acid, gabapentin and topiramate have shown to be excellent treatment for alcohol withdrawal and for the prevention of alcohol relapse. Although none of these agents have been approved by the FDA yet, there is growing evidence in the literature to support their use.

  7. Imidazenil: a low efficacy agonist at alpha1- but high efficacy at alpha5-GABAA receptors fail to show anticonvulsant cross tolerance to diazepam or zolpidem.

    Science.gov (United States)

    Auta, James; Impagnatiello, Francesco; Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio

    2008-08-01

    Whereas advances in the molecular biology of GABA(A) receptor complex using knock-out and knock-in mice have been valuable in unveiling the structure, composition, receptor assembly, and several functions of different GABA(A) receptor subtypes, the mechanism(s) underlying benzodiazepine (BZ) tolerance and withdrawal remain poorly understood. Studies using specific GABA(A) receptor subunit knock-in mice suggest that tolerance to sedative action of diazepam requires long-term activation of alpha1 and alpha5 GABA(A) receptor subunits. We investigated the role of long-term activation of these GABA(A) receptor subunits during anticonvulsant tolerance using high affinity and high intrinsic efficacy ligands for GABA(A) receptors expressing the alpha5 subunit (imidazenil) or alpha1 subunit (zolpidem), and a non-selective BZ recognition site ligand (diazepam). We report here that long-term activation of GABA(A) receptors by zolpidem and diazepam but not by imidazenil elicits anticonvulsant tolerance. Although anticonvulsant cross-tolerance occurs between diazepam and zolpidem, there is no cross-tolerance between imidazenil and diazepam or zolpidem. Furthermore, diazepam or zolpidem long-term treatment decreased the expression of mRNA encoding the alpha1 GABA(A) receptor subunit in prefrontal cortex by 43% and 20% respectively. In addition, diazepam but not zolpidem long-term treatment produced a 30% increase in the expression of the alpha5 GABA(A) receptor subunit mRNA in prefrontal cortex. In contrast, imidazenil which is devoid of anticonvulsant tolerance does not elicit significant changes in the expression of alpha1 or alpha5 GABA(A) receptor subunit. These findings suggest that long-term activation of GABA(A) receptors containing the alpha1 or other subunits but not the alpha5 receptor subunit is essential for the induction of anticonvulsant tolerance.

  8. Modulatory effects of nitric oxide-active drugs on the anticonvulsant activity of lamotrigine in an experimental model of partial complex epilepsy in the rat

    Directory of Open Access Journals (Sweden)

    Ferraro Giuseppe

    2007-07-01

    Full Text Available Abstract Background The effects induced by administering the anticonvulsant lamotrigine, the preferential inhibitor of neuronal nitric oxide synthase 7-nitroindazole and the precursor of NO synthesis L-arginine, alone or in combination, on an experimental model of partial complex seizures (maximal dentate gyrus activation were studied in urethane anaesthetized rats. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle and maximal dentate gyrus activation latency, duration and post-stimulus afterdischarge duration were evaluated. Results Either Lamotrigine (10 mg kg-1 or 7-nitroindazole (75 mg kg-1 i.p. administration had an anticonvulsant effect, significantly reducing the number of animals responding to angular bundle stimulation. On the contrary, i.p. injection of L-arginine (1 g kg-1 induced an aggravation of the epileptiform phenomena, demonstrated by the significant augmentation of the duration of both maximal dentate activation and afterdischarge. Furthermore, the injection of lamotrigine and 7-nitroindazole in combination significantly increased the anticonvulsant effects induced by the same drugs separately, either reducing the number of responding animals or decreasing both maximal dentate gyrus activation and afterdischarge durations. On the contrary, the combined treatment with L-arginine and lamotrigine did not modify the maximal dentate gyrus activation parameters suggesting an adversative effect of L-arginine-increased nitric oxide levels on the lamotrigine-induced anticonvulsant action. Conclusion The present results indicate that the nitrergic neurotransmission exerts a significant modulatory role in the control of the development of paroxystic phenomena in the maximal dentate gyrus activation model of epilepsy. Finally, our data suggest a functional relationship between the nitric oxide system and the anticonvulsant effect of lamotrigine which could be enhanced by

  9. Anticonvulsant Effect of the Aqueous Extract and Essential Oil of Carum Carvi L. Seeds in a Pentylenetetrazol Model of Seizure in Mice

    Science.gov (United States)

    Showraki, Alireza; Emamghoreishi, Masoumeh; Oftadegan, Somayeh

    2016-01-01

    Background: Carum carvi L. (caraway), known as black zeera in Iran, has been indicated for the treatment of epilepsy in Iranian folk medicine. This study evaluated whether the aqueous extract and essential oil of caraway seeds have anticonvulsant effects in mice. Methods: The anticonvulsant effects of the aqueous extract (200, 400, 800, 1600, and 3200 mg/kg, i.p.) and essential oil (25, 50, 100, 200, and 400 mg/kg, i.p.) of caraway were assessed using pentylenetetrazol (PTZ; 95 mg/kg i.p.) induced convulsions. Diazepam (3 mg/kg) was used as positive control. The latency time before the onset of myoclonic, clonic, and tonic convulsions and the percentage of mortality were recorded. In addition, the effect of caraway on neuromuscular coordination was evaluated using the rotarod performance test. Results: The extract and essential oil dose-dependently increased the latency time to the onset of myoclonic (ED50, 1257 and 62.2 mg/kg, respectively) and clonic (ED50, 929 and 42.3 mg/kg, respectively) seizures. The extract and essential oil of caraway prevented the animals from tonic seizure with ED50s of 2142.4 and 97.6 mg/kg, respectively. The extract and essential oil of caraway protected 28.6 and 71.4% of the animals from PTZ-induced death, respectively, and had no significant effect on neuromuscular coordination. Conclusion: This study showed that the aqueous extract and essential oil of caraway had anticonvulsant properties. However, the essential oil was more potent and effective than was the aqueous extract as an anticonvulsant. Additionally, the anticonvulsant effect of caraway was not due to a muscle relaxant activity. These findings support the acclaimed antiepileptic effect of caraway in folk medicine and propose its potential use in petit mal seizure in humans. PMID:27217604

  10. Anticonvulsant Effect of the Aqueous Extract and Essential Oil of Carum Carvi L. Seeds in a Pentylenetetrazol Model of Seizure in Mice

    Directory of Open Access Journals (Sweden)

    Alireza Showraki

    2016-05-01

    Full Text Available Background: Carum carvi L. (caraway, known as black zeera in Iran, has been indicated for the treatment of epilepsy in Iranian folk medicine. This study evaluated whether the aqueous extract and essential oil of caraway seeds have anticonvulsant effects in mice. Methods: The anticonvulsant effects of the aqueous extract (200, 400, 800, 1600, and 3200 mg/kg, i.p. and essential oil (25, 50, 100, 200, and 400 mg/kg, i.p. of caraway were assessed using pentylenetetrazol (PTZ; 95 mg/kg i.p. induced convulsions. Diazepam (3 mg/kg was used as positive control. The latency time before the onset of myoclonic, clonic, and tonic convulsions and the percentage of mortality were recorded. In addition, the effect of caraway on neuromuscular coordination was evaluated using the rotarod performance test. Results: The extract and essential oil dose-dependently increased the latency time to the onset of myoclonic (ED50, 1257 and 62.2 mg/kg, respectively and clonic (ED50, 929 and 42.3 mg/kg, respectively seizures. The extract and essential oil of caraway prevented the animals from tonic seizure with ED50s of 2142.4 and 97.6 mg/kg, respectively. The extract and essential oil of caraway protected 28.6 and 71.4% of the animals from PTZ-induced death, respectively, and had no significant effect on neuromuscular coordination. Conclusion: This study showed that the aqueous extract and essential oil of caraway had anticonvulsant properties. However, the essential oil was more potent and effective than was the aqueous extract as an anticonvulsant. Additionally, the anticonvulsant effect of caraway was not due to a muscle relaxant activity. These findings support the acclaimed antiepileptic effect of caraway in folk medicine and propose its potential use in petit mal seizure in humans.

  11. Synthesis and pharmacological investigation of 2-(4-dimethylaminophenyl)-3,5-disubstituted thiazolidin-4-ones as anticonvulsants.

    Science.gov (United States)

    Senthilraja, Manavalan; Alagarsamy, Veerachamy

    2012-10-01

    A new series of 2-(4-dimethylaminophenyl)-3-substituted thiazolidin-4-one-5-yl-acetyl acetamides/benzamides were synthesized by the nucleophilic substitution of 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride with acetamide and benzamide. The starting material 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride was synthesized from 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetic acid, which in turn was prepared by one-pot reaction of amino component, p-dimethylamino benzaldehyde and mercapto succinic acid. The title compounds were investigated for their anticonvulsant activities; among the test compounds, compound 2-(4-dimethylaminophenyl)-3-phenylamino-thiazolidine-4-one-5-yl-acetylbenzamide (14) emerged as the most active compound of the series and as moderately more potent than the reference standard diazepam.

  12. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

    Science.gov (United States)

    Wang, Justin; Wu, Chiping; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2015-01-01

    Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging

  13. Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects

    Science.gov (United States)

    Beenen, L; Lindeboom, J; Trenite, D; Heimans, J; Snoek, F; Touw, D; Ader, H; van Alphen, H A M

    1999-01-01

    OBJECTIVE—To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.
METHODS—A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.
RESULTS—Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.
CONCLUSION—For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.

 PMID:10486394

  14. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

    Directory of Open Access Journals (Sweden)

    Justin Wang

    Full Text Available Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min. Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute

  15. The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator.

    Science.gov (United States)

    Fisher, Janet L

    2009-01-01

    Stiripentol (STP) has been used as co-therapy for treatment of epilepsy for many years. Its mechanism of action has long been considered to be indirect, as it inhibits the enzymes responsible for metabolism of other anti-convulsant agents. However, a recent report suggested that STP might also act at the neuronal level, increasing inhibitory GABAergic neurotransmission. We examined the effect of STP on the functional properties of recombinant GABA(A) receptors (GABARs) and found that it was a positive allosteric modulator of these ion channels. Its activity showed some dependence on subunit composition, with greater potentiation of alpha3-containing receptors and reduced potentiation when the beta1 or epsilon subunits were present. STP caused a leftward shift in the GABA concentration-response relationship, but did not increase the peak response of the receptors to a maximal GABA concentration. Although STP shares some functional characteristics with the neurosteroids, its activity was not inhibited by a neurosteroid site antagonist and was unaffected by a mutation in the alpha3 subunit that reduced positive modulation by neurosteroids. The differential effect of STP on beta1- and beta2/beta3-containing receptors was not altered by mutations within the second transmembrane domain that affect modulation by loreclezole. These findings suggest that STP acts as a direct allosteric modulator of the GABAR at a site distinct from many commonly used anti-convulsant, sedative and anxiolytic drugs. Its higher activity at alpha3-containing receptors as well as its activity at delta-containing receptors may provide a unique opportunity to target selected populations of GABARs.

  16. Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.

    Science.gov (United States)

    Parker, Michael H; Smith-Swintosky, Virginia L; McComsey, David F; Huang, Yifang; Brenneman, Douglas; Klein, Brian; Malatynska, Ewa; White, H Steve; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B; Maryanoff, Bruce E

    2009-12-10

    In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.

  17. Design, synthesis and anticonvulsant activity evaluation of 7-substituted-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xian-Yu; Quan, Zhe-Shan [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain; Yanbian Univ., Yanji, Jilin (China). Coll. of Pharmacy; Guan, Li-Ping; Zhang, Lei; Wei, Cheng-Xi; Piao, Hu-Ri [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain

    2009-07-01

    In this study, a novel series of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 7-hexyloxy-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one 4e was the most potent with median effective dose (ED{sub 50}) value of 6.6 mg kg-1, median toxicity dose (TD{sub 50}) of 39.4 mg kg{sup -1}, providing a protective index (PI=TD{sub 50} /ED{sub 50}) value of 6.0. (author)

  18. SYNTHESIS AND ANTICONVULSANT ACTIVITY OF NOVEL 2-AMINO-5-[4-CHLORO-2-(2-CHLOROPHENOXY PHENYL]-1,3,4-THIADIAZOLE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Foroumadi A.

    2007-05-01

    Full Text Available Several novel 2-amino-5-[4-chloro-2-(2-chlorophenoxyphenyl]-1,3,4-thiadiazole derivatives 4a-d were synthesized and their anticonvulsant activity was determined by evaluation of the ability of theses compounds to protect mice against convulsion induced by a lethal doses of pentylentetrazole (PTZ and maximal electroshock (MES. The result of anticonvulsant data shows that among the synthesized compounds, 5-[4-chloro-2-(2-chlorophenoxyphenyl]-N-ethyl-1,3,4-thiadiazol-2-amine 4c was the most active compound in both MES and PTZ tests with an ED50 of 20.11 and 35.33 mg/kg, respectively.

  19. R-(+)-ABP a novel derivative of 3-n-butyl-phthalide possesses anti-convulsant and neuroprotective properties in rodents

    Institute of Scientific and Technical Information of China (English)

    ELESTAGE; A.ROGER; L.DANOBER; ERENARD; X-Q.PENG; Z.GUO; J.T.ZHANG

    2004-01-01

    ABP is a novel phthalide derivative of 3-n-butyl-phthalide (NBP) synthesized at the Beijing Institute of Materia Medica.NBP was isolated from several plants including Apium graveolens Linn. The juice squeezed from fresh celery leaves has long been used in Southeastern China for the treatment of epilepsy, and NBP has been reported to possess anti-convulsant properties (Drugs Future 2000; 25: 16-23). The present study

  20. The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes

    Directory of Open Access Journals (Sweden)

    Rita Citraro

    2016-09-01

    Full Text Available The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAA receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy.

  1. Studies on the anticonvulsant activity of 4-alkyl-1,2,4-triazole-3-thiones and their effect on GABAergic system.

    Science.gov (United States)

    Plech, Tomasz; Kaproń, Barbara; Luszczki, Jarogniew J; Paneth, Agata; Siwek, Agata; Kołaczkowski, Marcin; Żołnierek, Maria; Nowak, Gabriel

    2014-10-30

    A series of 4-alkyl-5-(3-chlorobenzyl/2,3-dichlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1a-14a) were designed, synthesized and screened for their anticonvulsant properties. Moreover, the acute adverse-effect profile of the active compounds (1a-7a, 12a) with respect to impairment of motor performance was evaluated in the chimney test. Among 4-alkyl-5-(3-chlorobenzyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones, ethyl, butyl, pentyl, hexyl, and heptyl derivatives administered intraperitoneally in a dose of 300 mg/kg protected 100% of the tested animals at four pretreatment times (i.e., 15, 30, 60, 120 min). Taking into account the median effective and toxic doses as well as the time-course profile of anticonvulsant activity, 5-(3-chlorobenzyl)-4-hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (4a) was proposed as the best tolerated and the most promising potential drug candidate. Finally, a radioligand binding assay was used to check whether the anticonvulsant activity of 4-alkyl-1,2,4-triazole-3-thiones was a result of their interactions (direct or allosteric) with GABAA receptor complex and/or their affinity to benzodiazepine (BDZ) binding sites.

  2. Anticonvulsant action of Dingxianning Keliji%定痫宁颗粒剂抗癫痫作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    周大兴; 金国梁; 方伟

    2001-01-01

    目的:研究定痫宁颗粒剂的抗癫痫作用。方法:采用海人酸(KA)所致癫痫、最大电休克发作(maximal electroshock seizure, MES)、戊四氮最小阈发作(metrazol minimal threshold seizure, MET)以及士的宁惊厥为指标,观察定痫宁的抗癫痫作用。结果:定痫宁能显著抑制海人酸所致大鼠癫痫发作,对抗大鼠、小鼠的最大电休克发作和小鼠的戊四氮最小阈发作、士的宁的惊厥反应。结论:定痫宁具有明显的抗癫痫作用。%Objective: To observe the anticonvulsant action of Dingxianning Keliji (DXNKLJ). Methonds: The anticonvulsant action of DXNKLJ was investigated in Maximal Electroshock seizure (MES), Kainic acid (Ka)-induced convusion, strychine-induced convulsion, and Metrazol threshold seizure (MET), respectively. Results: DXNKLJ (24、16、8g/kg) had an obvious effect against MES in both mice or rats and MET in mice, had an antagonism tokainic acid、strychinine-induced convuision also. Conclusion: DXNKLJ had an obvious anticonvulsant effect.

  3. Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

    Science.gov (United States)

    Malik, Sachin; Ahuja, Priya; Sahu, Kapendra; Khan, Suroor Ahmad

    2014-09-12

    A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs.

  4. Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Capacio, B.R.; Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Gales, V.

    1992-12-31

    The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.

  5. [Stimulation of gastric mucosa afferents by phenylephrine potentiates anticonvulsive and eliminates sedative action of sodium valproate in the pentylenetetrazol kindling model in rats].

    Science.gov (United States)

    Serdiuk, S E; Gmiro, V E; Veselkina, O S

    2014-01-01

    Sodium valproate after chronic intragastric administration in the high dose of 100-200 mg/kg eliminates generalized clonic-tonic pentylenetetrazol seizures in 100 % of rats, but only in 33-57 % of rats it prevents local clonic kindling seizures. Strong sedation is induced by the specified doses of sodium valproate. The combined oral chronic administration of phenylephrine in threshold, noneffective alone dose of 0.2 mg/kg and sodium valproate in high doses of 100 mg/kg and 200 mg/kg potentiates anticonvulsive action of sodium valproate, because prevents both clonic-tonic kindling. seizures in 100 % of rats and clonic kindling seizures in 86-100 % of rats, and also it increases in 1.7-1.9 times anticonvulsive activity of valproate. The specified combinations of sodium valproate with phenylephrine do not produce the sedative side effect. The basis of the mechanism of potentiation of anticonvulsive action and elimination of sedative action of sodium valproate in high doses is the stimulation of gastric mucosa afferents by phenylephrine.

  6. Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Lamb, John G; White, H Steve; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2007-01-01

    N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide (OM-TMCD) is a methoxyamide derivative of a cyclopropyl analogue of valproic acid (VPA). The structural considerations used in the design of OM-TMCD were aimed to enhance OM-TMCD anticonvulsant potency (compared to VPA) and to prevent VPA's two life-threatening side effects, i.e., induction of neural tube defects (NTDs) and hepatotoxicity. Following i.p. administration to rats OM-TMCD demonstrated a broad spectrum of anticonvulsant activity and showed better potency than VPA in the maximal electroshock seizure and subcutaneous pentylenetetrazole tests as well as in the hippocampal kindling model. OM-TMCD was inactive in the mouse 6-Hz test at 100 mg/kg dose. Teratogenicity studies performed in a SWV/Fnn-mouse model for VPA-induced-exencephaly showed that on the equimolar basis OM-TMCD possesses the same fetal toxicity and ability to induce NTDs as VPA, but since OM-TMCD is a much more potent anticonvulsant its activity/exencephaly formation ratio appears to be much more beneficial than that of VPA. OM-TMCD was found to be non-mutagenic and non-pro-mutagenic in the Ames test. It showed a beneficial pharmacokinetic profile in rats, having a high oral bioavailability of 75% and satisfactory values of clearance and volume of distribution. These results support further studies to fully characterize the therapeutic potential of OM-TMCD.

  7. Anticonvulsant and procognitive properties of the non-imidazole histamine H3 receptor antagonist DL77 in male adult rats.

    Science.gov (United States)

    Sadek, Bassem; Saad, Ali; Subramanian, Dhanasekaran; Shafiullah, Mohamed; Łażewska, Dorota; Kieć-Kononowiczc, Katarzyna

    2016-07-01

    It has become clear that histamine H3 receptors (H3Rs) are implicated in modulating epilepsy and memory in laboratory animals. The new non-imidazole H3R antagonist DL77 has excellent selectivity profile and shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 values of 2.1 ± 0.2 mg/kg and 8.4 ± 1.3 [nM], respectively. In the present study, the anticonvulsant effects of DL77 on maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models were investigated. Moreover, the procognitive properties of DL77 were tested on acquisition, consolidation and retrieval processes in a one-trial inhibitory avoidance task in male Wistar rats. The results indicate that DL77 (5, 10, and 15 mg/kg, i.p.) significantly and dose-dependently reduced MES-induced seizure duration, whereas no protection was observed in PTZ- or STR-induced seizures. Importantly, the protective action observed for DL77 in MES-induced seizure was comparable to that of the reference antiepileptic drug (AED) phenytoin (PHT), and was also reversed when rats were pretreated with the CNS penetrant pyrilamine (PYR) (10 mg/kg, i.p.), or with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg, i.p.). Furthermore, the procognitive studies indicate that acute pre-training systemic administration of DL77 (2.5 mg/kg, i.p.) facilitated acquisition, whereas pre-testing acute administration of DL77 (5 and 10 mg/kg, i.p.) improved retrieval. Interestingly, the procognitive effect of DL77 on retrieval was completely abrogated when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL) but not the centrally acting H1R antagonist PYR, indicating that histaminergic pathways through activation of H2Rs appear to be participating in neuronal circuits involved in retrieval processes. Taken together, our results show that DL77 demonstrates anticonvulsant properties in the MES-induced seizure model and improves cognitive

  8. Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage.

    Science.gov (United States)

    Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio; Auta, James

    2009-02-27

    Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at alpha1- but is a high efficacy positive allosteric modulator at alpha5-containing GABA(A) receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or

  9. Study of the structural and electronic properties of valproic acid and new derivatives used as anticonvulsant agents.

    Science.gov (United States)

    Comelli, Nieves C; Lobayan, Rosana M; Castro, Eduardo A; Jubert, Alicia H

    2011-03-10

    The conformational and electronic characteristics of the polar O(9)═C(8)-X(10) moiety in the anticonvulsant valproic acid (Vpa) drug and some of their amides and ester derivatives are analyzed at the B3LYP level using the 6-31+G(d,p) and 6-311++G(d,p) 6d,10f basis sets. Exploring the delocalization of the electron density of the O(9)═C(8)-X(10) moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O(9)═C(8)-X(10) is accompanied by a three-dimensional arrangement of donor and acceptor proton units closing nearly planar pseudorings of four, five, and six members arising from stabilizing interactions around the O(9)═C(8)-X(10) backbone. From the structure-property relationship analysis, we explain the origin of the change in the structural parameters and atomic charges in the polar moiety.

  10. Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors

    Directory of Open Access Journals (Sweden)

    Shariati-Rad Schwann

    2007-08-01

    Full Text Available Abstract Background Passion flower (Passiflora incarnata is used in traditional medicine of Europe and South America to treat anxiety, insomnia and seizure. Recently, it has shown antianxiety and sedative effects in human. Methods In this study, anticonvulsant effects of hydro- alcoholic extract of Passiflora, Pasipay, were examined by using pentylentetrazole model (PTZ on mice. Pasipay, diazepam, and normal saline were injected intraperitoneally at the doses 0.4–0.05 mg/kg, 0.5–1 mg/kg and 10 ml/kg respectively 30 minutes before PTZ (90 mg/kg, i.p. The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For investigating the mechanism of Pasipay, flumazenil (2 mg/kg, i.p and naloxone (5 mg/kg, i.p were also injected 5 minutes before Pasipay. Results An ED50 value of Pasipay in the PTZ model was 0.23 mg/kg (%95 CL: 0.156, 0.342. Pasipay at the dose of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizures compared to saline group (p Conclusion It seems that Pasipay could be useful for treatment absence seizure and these effects may be related to effect of it on GABAergic and opioid systems. More studies are needed in order to investigate its exact mechanism.

  11. New benzo[d]thiazol-2-yl-aminoacetamides as potential anticonvulsants: synthesis, activity and prediction of molecular properties.

    Science.gov (United States)

    Ali, Ruhi; Siddiqui, Nadeem

    2015-04-01

    A series of N-(substituted-2-oxo-4-phenylazetidin-1-yl)-2-((6-substitutedbenzo[d]thiazol-2-yl)amino)acetamide derivatives were synthesized using pharmacophoric features with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain, the nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). The synthesized molecules were initially screened for anticonvulsant activity using the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazole test in albino mice. An acute neurotoxicity study on the synthesized molecules was also carried out using the rotarod test. The results of these tests revealed that two compounds, 5b and 5q, showed promising activity with ED50 values of 15.4 and 18.6 mg/kg and protective indices of 20.7 and 34.9 in the MES test, respectively, which are found to be approximately fourfold higher than those of the standard drugs phenytoin (6.9) and carbamazepine (8.1). These molecules may act as lead of the designed scheme. The pharmacokinetic profiles of all the synthesized compounds were estimated using Molinspiration software. None of the compounds violated Lipinski's "rule of five". The possible structure-activity relationship was discussed. In conclusion, this manuscript shows that the developed model has a highly prognostic power for the further investigation of better benzothiazole derivatives for future discovery and development.

  12. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

    Science.gov (United States)

    Schiebler, Mark; Brown, Karen; Hegyi, Krisztina; Newton, Sandra M; Renna, Maurizio; Hepburn, Lucy; Klapholz, Catherine; Coulter, Sarah; Obregón-Henao, Andres; Henao Tamayo, Marcela; Basaraba, Randall; Kampmann, Beate; Henry, Katherine M; Burgon, Joseph; Renshaw, Stephen A; Fleming, Angeleen; Kay, Robert R; Anderson, Karen E; Hawkins, Phillip T; Ordway, Diane J; Rubinsztein, David C; Floto, Rodrigo Andres

    2015-02-01

    Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection.

  13. Anticonvulsants Based on the α-Substituted Amide Group Pharmacophore Bind to and Inhibit Function of Neuronal Nicotinic Acetylcholine Receptors.

    Science.gov (United States)

    Krivoshein, Arcadius V

    2016-03-16

    Although the antiepileptic properties of α-substituted lactams, acetamides, and cyclic imides have been known for over 60 years, the mechanism by which they act remains unclear. I report here that these compounds bind to the nicotinic acetylcholine receptor (nAChR) and inhibit its function. Using transient kinetic measurements with functionally active, nondesensitized receptors, I have discovered that (i) α-substituted lactams and cyclic imides are noncompetitive inhibitors of heteromeric subtypes (such as α4β2 and α3β4) of neuronal nAChRs and (ii) the binding affinity of these compounds toward the nAChR correlates with their potency in preventing maximal electroshock (MES)-induced convulsions in mice. Based on the hypothesis that α-substituted amide group is the essential pharmacophore of these drugs, I found and tested a simple compound, 2-phenylbutyramide. This compound indeed inhibits nAChR and shows good anticonvulsant activity in mice. Molecular docking simulations suggest that α-substituted lactams, acetamides, and cyclic imides bind to the same sites on the extracellular domain of the receptor. These new findings indicate that inhibition of brain nAChRs may play an important role in the action of these antiepileptic drugs, a role that has not been previously recognized.

  14. Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts.

    Science.gov (United States)

    Stone, W E; Javid, M J

    1988-09-01

    The anticonvulsive action of lidocaine was tested in mice against a series of convulsants, and its profile of action compared with that of phenytoin. Both agents antagonized seizures induced by ouabain or glutamate (injected i.c.b.), effects attributable to reduction of the sodium conductance of neuronal membranes. Lidocaine and phenytoin were relatively ineffective against convulsants that act on synaptic chloride channels via the GABA-ionophore receptor complex. At higher dose levels, both lidocaine and phenytoin are excitatory within limited ranges. Lidocaine-induced seizures were potentiated by phenytoin, and antagonized by chlordiazepoxide, phenobarbital, valproate, trimethadione and muscimol, but not by ethosuximide. This profile of action is similar to that of bicuculline, suggesting that lidocaine may bind to the GABA recognition site and to another site in the GABA-ionophore receptor complex. Phenytoin-induced excitation was antagonized by chlordiazepoxide, less effectively by phenobarbital or trimethadione, only minimally by valproate, and not by trimethadione or muscimol. Phenytoin is known to bind to picrotoxin and benzodiazepine receptor sites; these findings suggest that it may be excitatory at one or both of these sites.

  15. Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the pilocarpine model of Status epilepticus.

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    Chiara Lucchi

    Full Text Available In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a. This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2 in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05 and JMV-1843 (P<0.01 were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05 the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups. These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.

  16. Protective but Not Anticonvulsant Effects of Ghrelin and JMV-1843 in the Pilocarpine Model of Status epilepticus

    Science.gov (United States)

    Lucchi, Chiara; Curia, Giulia; Vinet, Jonathan; Gualtieri, Fabio; Bresciani, Elena; Locatelli, Vittorio; Torsello, Antonio; Biagini, Giuseppe

    2013-01-01

    In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45±0.07 mm2 in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus. PMID:24015271

  17. Synthesis and anticonvulsant activity of 7-benzylamino-4, 5-dihydro- [ 1, 2, 4] triazolo[ 4, 3-a] quinolines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A series of 7-substituted-benzylamino-4, 5-dihydro-[ 1,2, 4]triazolo[4, 3-a] quinoline derivatives was synthesized and evaluated for their anticonvulsant activity. The subcutaneous pentylenetetrazole test (sc-PTZ) demonstrated that the most effective compound in controlling the sc-PTZ induced seizure was 7-(3-bromine-benzylamino)-4, 5-dihydro-[ 1,2, 4]triazolo[4, 3-a]quinoline (4j) with an ED50 of 5.0 mg/kg and the PI of 20.7, which was also safer than the reference drugs. And the maximal electroshock test (MES)demonstrated that among these derivatives, 7-(3-fluorobenzylamino) -4, 5-dihydro-[ 1,2, 4]trizolo[4, 3-a]quinoline (4i), with an ED50 of 15.3 mg/kg and the PI of 7.2, was the safest in MES test. Furthermore, their neurotoxicities were measured by the rotarod neurotoxicity test, and the results showed that all derivatives possessed lower neurotoxicity.

  18. Assessing Anticonvulsant Effect of Aqueous Extract of Datura Stramonium Seed on PTZ-Induced Seizures in the Male Mice

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    S Namvar Aghdash

    2015-11-01

    Full Text Available Background: Epilepsy is one of the most common neurological disorders that affect social, economic and biological aspects of the human life. Many epileptic patients have uncontrolled seizures and medication-related side effects despite adequate pharmacological treatment. The use of plant extracts is proposed as a therapeutic modality in order to treat different diseases. Datura plant has long been used in the traditional medicine in regard with some nervous disorders like epilepsy. Thus, this study aimed to provide a scientific basis investigating the effect of Datura aqueous extract on PTZ-induced seizures in the male mice. Methods: In this experimental study, 40 male mice were randomly allocated into 5 equal groups including: one control group, one sham group and three experimental groups. The experimental groups received 50, 100 and 150 mg/kg of aqueous extract of Datura Stramonium seed via gavage for 30 days, and the sham group received stilled water via gavage. Pentylenetetrazol (PTZ 35 mg/kg, i.p were injected into control, sham and experimental groups 30 minutes after gavage in order to induce the seizure. Then latency time of seizure onset, seizure duration and seizure phases were measured and recorded in the experimental, sham and control groups. The data analysis was carried out via one way ANOVA and Tukey post-hoc tests.  Moreover, difference less than 0.05 (P<0.05 was considered significant. Results: The study findings revealed that the aqueous extract of Datura Stramonium seed produced a significant effect on PTZ-induced seizure. In addition, Datura increases latency time of seizure onset (P˂0.01, inhibits progress of seizure stages (P˂0.05 and decreases seizure duration (P˂0.001. Conclusion: The results obtained from the present study indicated that extract of this plant has anticonvulsant effects on PTZ-induced seizure. As a result, it seems to be beneficial to the epilepsy treatment.

  19. The Anticonvulsant Effect of Transcutaneous Auricular Vagus Nerve Stimulation is Associated with Balancing the Autonomic Dysfunction in Rats

    Institute of Scientific and Technical Information of China (English)

    Wei He; Xiao-Yu Wang; Hong Shi; Yang-Shuai Su; Xiang-Hong Jing; Bing Zhu

    2016-01-01

    Objective: The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats. Methods: Healthy adult male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of 10%urethane. Seizures were evoked by intraperitoneal injection of pentylenetetrazol (PTZ, 60 mg/kg). Femoral vein catheterization was performed for injection of sympathetic agonist and antagonists. Bipolar globe silver electrodes were utilized for epidural EEG recording. Three needles were inserted separately in subcutaneous muscles of left anterior limb, right anterior limb, and left hind limb to record ECG signals. ta-VNS was performed at auricular concha. Results: In comparison with preictal state, the mean heart rate (HR) increased slightly during epileptic seizures (P<0.05). In comparison with ictal state, the mean HR decreased a little at postictal state (P<0.05). When continuous epileptic seizures in EEG traces occurred (in ictal state), vein injection of propranolol hydrochloride (sympathetic antagonist) suppressed the epileptic seizures. When epileptic seizures occurred rarely (in postictal state), vein injection of adrenaline hydrochloride (sympathetic agonist) exacerbated the epileptic seizures. In comparison with pre-stimulation, the integral of EEG traces after ta-VNS decreased (P<0.05), the mean HR decreased (P<0.05), and the high power (HF) of HRV increased (P<0.05) after ta-VNS. Conclusion: The results showed that autonomic dysfunction occurred in epileptic rats characterized by enhanced sympathetic nerve activity. Epileptic seizures in EEG traces decreased, HR decreased and HF increased after ta-VNS, which indicated that ta-VNS may suppress epileptic seizures via balancing the autonomic dysfunction.

  20. Evaluation of the anticonvulsant activity of the essential oil of Myrothamnus moschatus in convulsion induced by pentylenetetrazole and picrotoxin

    Institute of Scientific and Technical Information of China (English)

    Emmanuel Randrianarivo; Filippo Maggi; Marcello Nicoletti; Philippe Rasoanaivo

    2016-01-01

    Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus (M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models. Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses (0.1–0.8 mL/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route. Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded. Results: The essential oil at 0.8 mL/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pen-tylenetetrazole alone, the mortality was 100%within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100%died in those that had been pre-treated with the oil. Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.

  1. Evaluation of the anticonvulsant activity of the essential oil of Myrothamnus moschatus in convulsion induced by pentylenetetrazole and picrotoxin

    Institute of Scientific and Technical Information of China (English)

    Emmanuel Randrianarivo; Filippo Maggi; Marcello Nicoletti; Philippe Rasoanaivo

    2016-01-01

    Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses(0.1–0.8 m L/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route.Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded.Results: The essential oil at 0.8 m L/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pentylenetetrazole alone, the mortality was 100% within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100% died in those that had been pre-treated with the oil.Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.

  2. Saikosaponin a mediates the anticonvulsant properties in the HNC models of AE and SE by inhibiting NMDA receptor current and persistent sodium current.

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    Yun-Hong Yu

    Full Text Available Epilepsy is one of the most common neurological disorders, yet its treatment remains unsatisfactory. Saikosaponin a (SSa, a triterpene saponin derived from Bupleurum chinensis DC., has been demonstrated to have significant antiepileptic activity in a variety of epilepsy models in vivo. However, the electrophysiological activities and mechanisms of the antiepileptic properties of SSa remain unclear. In this study, whole-cell current-clamp recordings were used to evaluate the anticonvulsant activities of SSa in the hippocampal neuronal culture (HNC models of acquired epilepsy (AE and status epilepticus (SE. Whole-cell voltage-clamp recordings were used to evaluate the modulation effects of SSa on NMDA-evoked current and sodium currents in cultured hippocampal neurons. We found that SSa effectively terminated spontaneous recurrent epileptiform discharges (SREDs in the HNC model of AE and continuous epileptiform high-frequency bursts (SE in the HNC model of SE, in a concentration-dependent manner with an IC(50 of 0.42 µM and 0.62 µM, respectively. Furthermore, SSa significantly reduced the peak amplitude of NMDA-evoked current and the peak current amplitude of I(NaP. These results suggest for the first time that the inhibitions of NMDA receptor current and I(NaP may be the underlying mechanisms of SSa's anticonvulsant properties, including the suppression of SREDs and SE in the HNC models of AE and SE. In addition, effectively abolishing the refractory SE implies that SSa may be a potential anticonvulsant candidate for the clinical treatment of epilepsy.

  3. Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

    Science.gov (United States)

    Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

    2014-07-24

    We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

  4. Long-term studies on anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice. I. Comparison of diazepam, clonazepam, clobazam and abecarnil.

    Science.gov (United States)

    Löscher, W; Rundfeldt, C; Hönack, D; Ebert, U

    1996-11-01

    We have reported recently that the seizure model and experimental protocol may markedly influence anticonvulsant tolerance and withdrawal characteristics of benzodiazepine (BDZ) receptor ligands so that predictions on tolerance and dependence liability of novel drugs should be based on a battery of chronic experiments. In the present study, we compared BDZ receptor ligands with different intrinsic efficacy and/or gamma-aminobutyric acidA/BDZ receptor subtype selectivity in two seizure models, by using different experimental approaches to assess the tolerance and dependence liability. In one approach, mice were chronically treated with either diazepam, clonazepam, clobazam or the novel anxiolytic and anticonvulsant beta-carboline derivative abecarnil for 4 weeks, at doses which were about equipotent to increase the threshold for myoclonic seizures induced by pentylenetetrazole. Anticonvulsant activity was determined several times during the period of chronic treatment as well as up to 2 weeks after termination of treatment in the same group of animals per drug. The threshold for electroshock-induced tonic seizures was used as a second seizure model in separate groups of mice. In another approach, drug treatment protocols were the same but the seizures were induced only twice during the 4-week period of treatment to reduce the number of trials which could lead to "learned" tolerance. In additional groups of mice, the seizure thresholds were only determined before and after the period of treatment to assess whether repeated seizure induction during the chronic treatment affects the development of dependence. All four drugs lost anticonvulsant activity during the chronic treatment in the different models and experimental approaches, without indication for a significant involvement of learned tolerance. However, marked protocol-related differences were seen with respect to withdrawal symptoms, i.e., measures of physical dependence-inducing properties of the different

  5. Design, synthesis and evaluation of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylates as potential anticonvulsants and their molecular properties prediction.

    Science.gov (United States)

    Prasanthi, G; Prasad, K V S R G; Bharathi, K

    2013-08-01

    The present study is on the development of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylate derivatives as isosteric analogues of isradipine and nifedipine, by the replacement of benzofurazanyl and 2-nitrophenyl groups respectively with benzo[d][1,3]dioxo-6-yl group, as potential anticonvulsants. Fivfteen new derivatives (8a-8o) were synthesized and tested for anticonvulsant activity using maximal electroshock and subcutaneous pentylenetetrazole induced seizure methods. Compound 8f possessing free NH group in 1,4-dihydropyridine ring, diethyl ester functionality at the positions 3 and 5 showed significant anticonvulsant and antioxidant activities. This was also supported by molecular properties prediction data. Selected compounds were evaluated for antinociceptive activity in capsaicin induced nociception assay at 10 mg/kg body weight, but displayed no significant activity at the tested dose.

  6. Doenças de Dupuytren e de Ledderhose associadas ao uso crônico de anticonvulsivantes: relato de caso Dupuytren's and Ledderhose's diseases associated with chronic use of anticonvulsants: case report

    Directory of Open Access Journals (Sweden)

    PATRÍCIA CORAL

    1999-09-01

    Full Text Available Relatamos o caso de um paciente que após uso crônico de anticonvulsivantes, sem epilepsia definida, desenvolveu contraturas das aponeuroses palmar (doença de Dupuytren e plantar (doença de Ledderhose. Discutimos as principais dessas complicações, os fatores predisponentes e sua estreita relação com o uso de anticonvulsivantes, particularmente de fenobarbital.We present the case of a patient that after chronic use of anticonvulsant drugs without proven epilepsy , developed Dupuytren's and Ledderhose's diseases. We discuss the most frequent predisponent factors, and their relationship with chronic use of anticonvulsants, particularly phenobarbitone.

  7. Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats

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    Sadek B

    2016-11-01

    performed for five selected test compounds. Also, lipophilicity using planar reversed-phase thin-layer chromatography method was included for better understanding of the molecular properties of the tested compounds. Additionally, the absorption, distribution, metabolism, and elimination and toxicity parameters were evaluated for the most promising compounds 2, 4, 6, 7, and 14 utilizing in vitro methods. These interesting results highlight the potential of H3R ligands as new antiepileptic drugs or as adjuvants to available epilepsy medications. Keywords: histamine H3 receptors, antagonists, anticonvulsant, R-(α-methyl-histamine, pyrilamine, zolantidine

  8. Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

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    Ricardo Alberto Moreno

    2004-10-01

    Full Text Available O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are

  9. Anti-convulsant action and amelioration of oxidative stress by Glycyrrhiza glabra root extract in pentylenetetrazole- induced seizure in albino rats

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    Bimalendu Chowdhury

    2013-01-01

    Materials and Methods: The aqueous and ethanol extract of Glycyrrhiza glabra was tested at three doses viz. 100, 200, and 400 mg/kg i.p. for its anti-convulsant activity using pentylenetetrazole (PTZ-induced seizure in rat. The effect of EEGG (400 mg/kg, i.p. on oxidative stress markers like malondialdehyde (MDA, superoxide dismutase (SOD, and catalase (CAT of rat brain tissue homogenate was tested. Results: The onset of seizure was delayed (P < 0.01 by all the three doses of EEGG, but the duration of convulsion was reduced (P < 0.01 only in higher dose level (200 and 400 mg/ kg, whereas AEGG up to 400 mg/kg did not alter any of the parameters significantly. Biochemical analysis of rat brain tissue revealed that MDA was increased (P < 0.01, whereas SOD and CAT were decreased (P < 0.01 in PTZ-induced seizure rat, whereas pre-treatment with EEGG (400 mg/kg decreased (P < 0.01 the MDA and increased (P < 0.01 both SOD and CAT, indicating attenuation of lipid peroxidation due to increase in antioxidant enzymes. Conclusion: The results demonstrated that EEGG poses anti-convulsant potential and ameliorates ROS induced neuronal damage in PTZ-induced seizure.

  10. Effect of acutely and chronically administered venlafaxine on the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model.

    Science.gov (United States)

    Borowicz, Kinga K; Gołyska, Dorota; Luszczki, Jarogniew J; Czuczwar, Stanislaw J

    2011-11-16

    The influence of acute and chronic treatments with intraperitoneal venlafaxine, a selective serotonin/norepinephrine reuptake inhibitor, on the anticonvulsant activity of selected antiepileptic drugs was studied in the maximal electroshock test in mice. Venlafaxine (12.5 and 25mg/kg), given either acutely or chronically, significantly increased the electroconvulsive threshold. Moreover, both acute and chronic venlafaxine, applied at the highest subprotective dose of 6.25mg/kg, enhanced the anticonvulsant effect of valproate, without affecting the protective action of carbamazepine, phenobarbital and phenytoin. The antidepressant did not affect brain concentration of valproate, indicating that the interaction between the two drugs seems pharmacodynamic in nature. Despite the lack of effect on the antielectroshock action of the remaining antiepileptics, acute venlafaxine increased the brain concentration of phenobarbital, while chronic venlafaxine reduced the brain level of phenytoin. In terms of adverse effects, acute/chronic venlafaxine and antiepileptic drugs alone, as well as their combinations, did not produce significant motor or long-term memory deficits in mice. Summing up, it seems that venlafaxine may be considered as a safe drug for the clinical use in patients with epilepsy and depressive disorders.

  11. 1-[(2-arylthiazol-4-yl)methyl]azoles as a new class of anticonvulsants: design, synthesis, in vivo screening, and in silico drug-like properties.

    Science.gov (United States)

    Ahangar, Nematollah; Ayati, Adile; Alipour, Eskandar; Pashapour, Arsalan; Foroumadi, Alireza; Emami, Saeed

    2011-11-01

    A series of novel thiazole incorporated (arylalkyl)azoles were synthesized and screened for their anticonvulsant properties using maximal electroshock and pentylenetetrazole models in mice. Among target compounds, 1-[(2-(4-chlorophenyl)thiazol-4-yl)methyl]-1H-imidazole (compound 4b), 1-[(2-phenylthiazol-4-yl)methyl]-1H-1,2,4-tria-zole (8a), and its 4-chlorophenyl analog (compound 8b) were able to display noticeable anticonvulsant activity in both pentylenetetrazole and maximal electroshock tests with percentage protection range of 33-100%. A computational study was carried out for prediction of pharmacokinetics properties and drug-likeness. The structure-activity relationship and in silico drug relevant properties (molecular weight, topological polar surface area, clog P, hydrogen bond donors, hydrogen bond acceptors, and log BB) confirmed that the compounds were within the range set by Lipinski's rule-of-five, and possessing favorable physicochemical properties for acting as CNS-drugs, making them potentially promising agents for epilepsy therapy.

  12. In silico validation and structure activity relationship study of a series of pyridine-3-carbohydrazide derivatives as potential anticonvulsants in generalized and partial seizures.

    Science.gov (United States)

    Sinha, Reema; Sara, Udai Vir Singh; Khosa, Ratan Lal; Stables, James; Jain, Jainendra

    2013-06-01

    A series of twelve compounds (Compounds RNH1-RNH12) of acid hydrazones of pyridine-3-carbohydrazide or nicotinic acid hydrazide was synthesized and evaluated for anticonvulsant activity by MES, scPTZ, minimal clonic seizure and corneal kindling seizure test. Neurotoxicity was also determined for these compounds by rotarod test. Results showed that halogen substitution at meta and para position of phenyl ring exhibited better protection than ortho substitution. Compounds RNH4 and RNH12, were found to be the active analogs displaying 6Hz ED50 of 75.4 and 14.77 mg/kg while the corresponding MES ED50 values were 113.4 and 29.3 mg/kg respectively. In addition, compound RNH12 also showed scPTZ ED50 of 54.2 mg/kg. In the series, compound RNH12 with trifluoromethoxy substituted phenyl ring was the most potent analog exhibiting protection in all four animal models of epilepsy. Molecular docking study has also shown significant binding interactions of these two compounds with 1OHV, 2A1H and 1PBQ receptors. Thus, N-[(meta or para halogen substituted) benzylidene] pyridine-3-carbohydrazides could be used as lead compounds in anticonvulsant drug design and discovery.

  13. A new class of anticonvulsants possessing 6 Hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides.

    Science.gov (United States)

    Kumar, Praveen; Tripathi, Laxmi

    2012-05-01

    A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides were designed & synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotorod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1H-benzotriazol-1-yl)acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. All the compounds exhibited no neurotoxicity. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.

  14. Effect of N-(m-bromoanilinomethyl-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    Directory of Open Access Journals (Sweden)

    Luszczki Jarogniew J.

    2014-06-01

    Full Text Available The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA] in the mouse maximal electroshock (MES-induced tonic seizure model. Tonic hind limb extension (seizure activity was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration delivered via ear-clip electrodes. BAM-IPPS administered (i.p. at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05. Lower doses of BAM-IPPS (50 and 100 mg/kg had no significant impact on the threshold for electroconvulsions in mice. Moreover, BAM-IPPS (100 mg/kg did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the mouse MES model. BAM-IPPS elevated the threshold for electroconvulsions in mice in a dosedependent manner. However, BAM-IPPS (100 mg/kg did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of BAM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.

  15. Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of some new 4,6-dimethoxy-5-(heterocyclesbenzofuran starting from naturally occurring visnagin

    Directory of Open Access Journals (Sweden)

    E.R. El-Sawy

    2014-12-01

    Full Text Available Novel 3-(4,6-dimethoxybenzofuran-5-yl-1-phenyl-1H-pyrazole-4-carboxaldehyde (3 and 3-chloro-3-(4,6-dimethoxybenzofuran-5-ylpropenal (4 were prepared via Vilsmeier–Haack reaction of 1-(4,6-dimethoxybenzofuran-5-ylethanone (1 and its hydrazone derivative 2. Reaction of compound 4 with some hydrazine derivatives, namely hydrazine hydrate, phenylhydrazine and benzylhydrazine hydrochloride led to the formation of pyrazole derivatives 5–8, respectively. On the other hand, reaction of compound 4 with thiourea, urea or guanidine gave the pyrimidine derivatives 9–11, respectively. Reaction of amino compound 11 with acetic anhydride, benzoyl chloride and benzenesulphonyl chloride yielded N-substituted pyrimidine derivatives 12–14, respectively. Reaction of diazonium salt of compound 11 with sodium azide afforded azidopyrimidine derivative 15, which upon reaction with ethyl acetoacetate gave 1,2,3-triazole derivative 16. Acid catalyzed reaction of 11 with p-nitrobenzaldehyde gave Schiff base 17, which cyclized upon reaction with thioglycolic acid or chloroacetyl chloride to give thiazolidin-4-one 18 and azetidin-2-one 19, respectively. The newly synthesized compounds were tested for their anti-inflammatory, analgesic and anticonvulsant activities. Depending on the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities.

  16. Anxiolytic and Anticonvulsant Effects on Mice of Flavonoids, Linalool, and -Tocopherol Presents in the Extract of Leaves of Cissus sicyoides L. (Vitaceae

    Directory of Open Access Journals (Sweden)

    Edvaldo Rodrigues de Almeida

    2009-01-01

    Full Text Available The aim of the present study is to demonstrate the anxiolytic and anticonvulsant effects of a hydroalcoholic extract obtained from the aerial parts of Cissus sicyoides L. (CS (Vitaceae on male and female mice using several behavioral assays. Groups of males and females treated via intraperitoneal (IP with doses of 300, 600, and 1000 mg/kg of the extract showed significant action in the elevated plus-maze (EPM, time spent in the open arms, and number of entries in the open arms. The board-hole test also showed a significant increase in the time spent in head-dipping and in marble-burying test of the number of marbles buried. The same treatment increased the duration of sleeping time induced by sodium pentobarbital and also showed a significant increase in protection against pentylenotetrazole-induced convulsions. These results indicate an anxiolytic and anticonvulsant-like action from C. sicyoides L. extract on mice, probably due to the action of flavonoid(s, Linalool, and -tocopherol present in the C. sicyoides leaves.

  17. Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice.

    Science.gov (United States)

    Rapacz, Anna; Obniska, Jolanta; Wiklik-Poudel, Beata; Rybka, Sabina; Sałat, Kinga; Filipek, Barbara

    2016-06-15

    The aim of the present experiments was to examine the anticonvulsant and antinociceptive activity of five new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in animal models of seizures and pain. The antiseizure activity was investigated in three acute models of seizures, namely, the maximal electroshock (MES), the subcutaneous pentylenetetrazole (scPTZ), and 6Hz psychomotor seizure tests in mice. The antinociceptive properties were estimated in the formalin model of tonic pain, and in the oxaliplatin-induced neuropathic pain model in mice. Considering drug safety evaluation, acute neurological toxicity was determined in the rotarod test. Three tested compounds (3, 4, and 7) displayed a broad spectrum of anticonvulsant activity and showed better protective indices than those obtained for MES/scPTZ/6Hz active reference drug - valproic acid. Furthermore, three compounds (3, 4, and 6) demonstrated a significant antinociceptive effect in the formalin test, as well as antiallodynic activity in the oxaliplatin-induced neuropathic pain model. Among the tested agents, compounds 3 and 4 displayed not only antiseizure properties, but also collateral prominent analgesic properties. The in vitro binding study indicated that the plausible mechanism of action of chosen compound (4) was the influence on neuronal voltage-sensitive sodium (site 2) and L-type calcium channels.

  18. Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

    Science.gov (United States)

    McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

    2013-11-27

    Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

  19. Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.

    Science.gov (United States)

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Zagaja, Mirosław; Andres-Mach, Marta; Kondrat-Wrobel, Maria W; Luszczki, Jarogniew J

    2015-03-01

    The purpose of this study was to determine the influence of WIN 55,212-2 mesylate (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various second- and third-generation antiepileptic drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes. Additionally, total brain antiepileptic drug concentrations were measured. Results indicate that WIN (5 mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide, oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model. Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had no impact on gabapentin or levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6Hz model. In conclusion, WIN in combination with gabapentin and levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the mouse psychomotor seizure model.

  20. A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Steven L., E-mail: stevenmiller17@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Aroniadou-Anderjaska, Vassiliki, E-mail: vanderjaska@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Figueiredo, Taiza H., E-mail: taiza.figueiredo.ctr@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Prager, Eric M., E-mail: eric.prager683@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Almeida-Suhett, Camila P., E-mail: camilapalmeida@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Apland, James P., E-mail: james.p.apland.civ@mail.mil [Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010 (United States); and others

    2015-04-15

    Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD{sub 50} of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2 × LD{sub 50}), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. - Highlights: • The LD{sub 50} of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD{sub 50} soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after

  1. Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice.

    Science.gov (United States)

    Salat, Kinga; Moniczewski, Andrzej; Salat, Robert; Janaszek, Monika; Filipek, Barbara; Malawska, Barbara; Wieckowski, Krzysztof

    2012-03-01

    Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABA(A), opioidergic μ and serotonergic 5-HT(1A) receptors. The total antioxidant capacity of LPP1 (1-10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo. In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED(50)=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD(50)=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its

  2. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

  3. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat.

    Science.gov (United States)

    Gao, Fei; Gao, Ying; Liu, Yang-Feng; Wang, Li; Li, Ya-Jun

    2014-01-01

    Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden.

  4. Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in neonatal rats

    OpenAIRE

    2014-01-01

    Levetiracetam (LEV) and tiagabine (TGB) are utilized for the treatment of seizures, including neonatal seizures. However, relatively little is known about the preclinical therapeutic profile of these drugs during brain development. The relative paucity of information regarding these drugs in neonatal animals may be due to their unusual profile of anticonvulsant action in experimental models. LEV and TGB are without effect against seizures in several common screening models (e.g., the maximal ...

  5. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)], E-mail: yamaaki@sahs.med.osaka-u.ac.jp; Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  6. Influence of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the anticonvulsant and acute side-effect potentials of clobazam, lacosamide, and pregabalin in the maximal electroshock-induced seizure model and chimney test in mice.

    Science.gov (United States)

    Florek-Luszczki, Magdalena; Zagaja, Miroslaw; Luszczki, Jarogniew J

    2015-08-01

    The influence of arachidonyl-2'-chloroethylamide (ACEA - a selective cannabinoid CB1 receptor agonist) on the anticonvulsant potency and acute adverse-effect potentials of clobazam, lacosamide, and pregabalin was determined in the maximal electroshock-induced seizure model and chimney test in mice. ACEA (2.5 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of pregabalin in the mouse maximal electroshock-induced seizure model by decreasing the median effective dose (ED50 ) of pregabalin from 125.39 to 78.06 mg/kg (P clobazam and lacosamide in the mouse maximal electroshock-induced seizure model. On the other hand, ACEA (2.5 mg/kg) did not affect acute adverse effects of clobazam, lacosamide or pregabalin, and the median toxic doses (TD50 ) for the studied anti-epileptic drugs in combination with ACEA did not differ from the TD50 values as determined for the drugs administered alone in the chimney test. In conclusion, ACEA ameliorates the pharmacological profile of pregabalin, when considering both the anticonvulsant and the acute adverse effects of the drug in preclinical study on animals. The combination of pregabalin with ACEA can be of pivotal importance for patients with epilepsy as a potentially advantageous combination if the results from this study translate into clinical settings.

  7. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

    Directory of Open Access Journals (Sweden)

    Gao F

    2014-11-01

    Full Text Available Fei Gao,1,* Ying Gao,2,* Yang-feng Liu,3 Li Wang,4 Ya-jun Li1 1Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 2Department of Radiotherapy Oncology, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Neurology, People’s Liberation Army No. 451 Hospital, Xi’an, People’s Republic of China; 4Department of Scientific Research, First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China *These authors contributed equally to this work Abstract: Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber, a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE, malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the

  8. Malformaciones congénitas en hijos de madres epilépticas con y sin tratamiento con anticonvulsivantes Congenital malformations in the offspring of epileptic mothers with and without anticonvulsant treatment

    Directory of Open Access Journals (Sweden)

    Jazmín Arteaga-Vázquez

    2012-12-01

    Full Text Available OBJETIVO: Determinar la frecuencia y tipo de malformaciones congénitas (MC en hijos de madres epilépticas (HME tratadas y no tratadas con anticonvulsivantes, la posible correlación anticonvulsivante/MC y la asociación con otras alteraciones del desarrollo. MATERIAL Y MÉTODOS: Estudio multicéntrico de casos y controles en 166 recién nacidos vivos HME identificados en 21 501 recién nacidos con MC y respectivos controles del Registro y Vigilancia Epidemiológica de Malformaciones Congénitas (RYVEMCE. RESULTADOS: La frecuencia de MC en HME tratadas fue mayor, (48.3% que en HME no tratadas (28.3%; (RM= 2.37 IC95% 1.08-5.40, p=0.03. Las MC más frecuentes fueron espina bífida, anomalías en reducción de miembros, labio/paladar hendido, microcefalia, anotia/microtia, hipospadias, paladar hendido, polidactilia, anoftalmia/microftalmia y onfalocele. No hubo diferencias entre uso de mono o politerapia. La difenilhidantoína, carbamazepina y ácido valproico fueron los anticonvulsivantes más utilizados. CONCLUSIONES: Los resultados confirman la teratogenicidad propia de la epilepsia y el efecto sinérgico de ciertos anticonvulsivantes, lo que evidencia la necesidad de un apropiado control periconcepcional de esta enfermedad y su tratamiento.OBJECTIVE: To determine the prevalence at birth and type of congenital malformations (CM in newborns of epileptic mothers (NEM treated and not treated with anticonvulsants, the correlation anticonvulsant/CM and other developmental disorders. MATERIALS AND METHODS: Multicenter case-control study, in 166 live births NEM diagnosed in 21 501 newborns with CM and respective controls from the Registro y Vigilancia Epidemiológica de Malformaciones Congénitas (RYVEMCE. RESULTS: The frequency of CM in NEM treated with anticonvulsants was higher (48.3% than in NEM of untreated mothers (28.3%, (OR= 2.37 IC95% 1.08-5.40, p=0.03. CMs most frequently found were: spina bifida, limb reduction defects, cleft lip palate

  9. Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

    Science.gov (United States)

    Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

    2016-02-01

    The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity/anticonvulsant

  10. Fast and easy extraction combined with high resolution-mass spectrometry for residue analysis of two anticonvulsants and their transformation products in marine mussels.

    Science.gov (United States)

    Martínez Bueno, M J; Boillot, C; Fenet, H; Chiron, S; Casellas, C; Gómez, E

    2013-08-30

    Environmental field studies have shown that carbamazepine (Cbz) is one of the most frequently detected human pharmaceuticals in different aquatic compartments. However, little data is available on the detection of this substance and its transformation products in aquatic organisms. This study was thus mainly carried out to optimize and validate a simple and sensitive analytical methodology for the detection, characterization and quantification of Cbz and oxcarbazepine (Ox), two anticonvulsants, and six of their main transformation products in marine mussels (Mytilus galloprovincialis). A modified QuEChERS extraction method followed by analysis with liquid chromatography coupled to high resolution mass spectrometry (HRMS) was used. The analyses were performed using two-stage fragmentation to reveal the different fragmentation pathways that are highly useful for the identification of isomeric compounds, a common problem when several transformation products are analyzed. The developed analytical method allowed determination of the target analytes in the lower ng/g concentration levels. The mean recovery ranged from 67 to 110%. The relative standard deviation was under 11% in the intra-day and 18% in the inter-day analyses, respectively. Finally, the method was applied to marine mussel samples collected from Mediterranean Sea cultures in southeastern France. Residues of the psychiatric drug Cbz were occasionally found at levels up to 3.5ng/g dw. Lastly, in this study, other non-target compounds, such as caffeine, metoprolol, cotinine and ketoprofen, were identified in the real samples analyzed.

  11. 活犀角与犀角抗惊厥作用的研究%A Study of the Anticonvulsive Effects Between Living Rhino Horn and Rhino Horn

    Institute of Scientific and Technical Information of China (English)

    冯润东; 曹蕾; 刘蕊; 宋冰雪; 刘静; 曹永孝

    2015-01-01

    目的:通过研究活犀角与犀角对小鼠的抗惊厥作用,探讨活犀角是否可以作为犀角的代用品。方法随机将280只小鼠(自主活动实验160只,抗惊厥实验120只),分为活犀角与犀角各4个剂量组(700、350、175、90 mg· kg-1),另设1个空白对照组和1个地西泮片阳性对照组,分别灌胃给予对应剂量的试验样品,连续2 d。末次给药后30 min后用自主活动记录仪记录各组20只小鼠自主活动;同时对各组另外15只小鼠采用尼可刹米诱发动物惊厥,记录小鼠出现惊厥的时间和死亡时间。结果自主活动记录结果显示,4个剂量的活犀角和犀角对小鼠均有兴奋作用;抗惊厥结果显示活犀角700、350、175、90 mg· kg-1和犀角350、175、90 mg· kg-1能明显降低小鼠的惊厥发生率和/或死亡率,且在350、175、90 mg· kg-1剂量下活犀角和犀角对小鼠的抗惊厥作用无显著性差异。结论在该验条件下,在抗惊厥作用方面可初步判断活犀角在350、175、90 mg· kg-1剂量可以作为犀角的代用品进行使用。%Objective To study of the anticonvulsive effects between living Rhino Horn and Rhino Horn and to explore whether living Rhino Horn could be used as a substitute of Rhino Horn.Methods The 280 mice were randomly divided into four groups of living Rhino Horn (700、350、175、90 mg· kg-1), four groups of Rhino Horn (700、350、175、90 mg· kg-1),a blank control group and a positive group of diazepam.The mice were gavaged with the corresponding dose of test sample for 2 consecutive days.Thirty minutes after last gavaged,the autonomic activeties of 20 mice in every group were records by the independent event recorder.The other 15 mice in every group were induced convulsion by Nikethamide.And then, it was recorded that the time of convulsion and the time of death of the mice.Results Independent activities and anticonvulsants, according to the results

  12. Greater Calcium Intake is Associated with Better Bone Health Measured by Quantitative Ultrasound of the Phalanges in Pediatric Patients Treated with Anticonvulsant Drugs

    Directory of Open Access Journals (Sweden)

    Vicente Vera

    2015-12-01

    Full Text Available We aimed to investigate and compare the effects of chronic antiepileptic therapy on bone health in pediatric patients using quantitative ultrasound of the phalanges (QUS and controlling for potential confounding factors, particularly nutrient intake. The amplitude-dependent speed of sound (Ad-SoS was measured in 33 epileptic children and 32 healthy children aged 6.5 ± 3.1 and 6.3 ± 1.1 (mean ± SD years, respectively. There were no significant differences in the demographics such as age, weight and height between epileptic children and the control group children. None of the children in the epileptic or the treatment group were found to have a vitamin D deficiency. There were no significant differences in laboratory tests between groups. Lower QUS figures were found in the epileptic children (p = 0.001. After further adjustment for potential confounders such age, height, weight, calcium intake, vitamin D intake, physical activity and sex, the differences remained significant (p < 0.001. After further classification of the participants based on the tertile of calcium intake, no significant differences were found between patients and healthy controls in the greatest tertile of calcium intake (p = 0.217. We conclude that anticonvulsant therapy using valproate may lead to low bone mass in children and that an adequate intake of calcium might counteract such deleterious effects.

  13. Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.

    Science.gov (United States)

    Ahsan, Mohamed Jawed; Khalilullah, Habibullah; Stables, James P; Govindasamy, Jeyabalan

    2013-06-01

    A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and evaluated for anticonvulsant activity according to the Antiepileptic Drug Development Programme (ADD) protocol. Some of the synthesized compounds showed significant activity in minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4c) was found to be the most active compound of the series showing 75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4f) showed protection in maximal electroshock (MES) seizure and subcutaneous metrazol (scMET) seizure at 300 mg/kg.

  14. Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

    Science.gov (United States)

    King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

    2011-10-13

    Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  15. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    Science.gov (United States)

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  16. 抗惊厥新药依佐加滨的药理与临床评价%Pharmacology and clinical evaluation of a new anticonvulsant, ezogabine

    Institute of Scientific and Technical Information of China (English)

    王来海; 张瑞岭; 张萍

    2012-01-01

    依佐加滨是首个治疗癫痫的神经元钾离子通道开放剂,己于2011年6月13日被美国FDA批准用于成人惊厥部分发作的治疗.其作用机制并未完全阐明,可能是通过稳定神经元钾离子通道使其保持“开放”状态,降低其若奋性而产生抗惊厥作用.其常见的不良反应有眩晕、嗜睡、乏力、意识错乱等.本文对依佐加滨的药理作用、药代动力学、药物相互作用、临床评价和安全性等进行介绍.%Ezogabine is the first neuronal potassium channel opener developed for the treatment of epilepsy. It was approved by the U. S. Food and Drug Administration on June 13, 2011 as an add-on medication to treat seizures associated with epilepsy in adults. The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. The drug may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an "open" state. Studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ family ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. The most common adverse effects were dizziness, drowsiness, fatigue and confusion, etc. The pharmacology, pharmaeokinetics, clinical evaluation, safety and drug interactions of ezogabine were reviewed in this paper.

  17. N-valproyl-L-phenylalanine as new potential antiepileptic drug: synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy.

    Science.gov (United States)

    De Caro, Viviana; Scaturro, Anna Lisa; Sutera, Flavia Maria; Avellone, Giuseppe; Schiera, Gabriella; Ferrantelli, Evelina; Carafa, Maria; Rizzo, Valerio; Carletti, Fabio; Sardo, Pierangelo; Giannola, Libero Italo

    2014-01-01

    Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, MS, (13)C and (1)H- NMR analyses. The Log D(pH7.4) value (0.19) indicated that new molecule was potentially able to cross biological membranes. The resistance to chemical and enzymatic hydrolysis of N-valproyl-L-phenylalanine was also assessed. All trials suggested that the compound, at the pH conditions of the entire gastro-intestinal tract, remained unmodified. Furthermore, the new compound did not undergo enzymatic cleavage both in plasma and in cerebral medium up to 24 h. The toxicity assay on primary cultures of astrocytes indicated that the synthetized conjugate was less toxic than both free VPA and L-Phenylalanine. In this paper, the anticonvulsant activity of the new compound against epileptic burst discharges evoked in vitro in rat hippocampal slices was also evaluated. These preliminary results underline that N-valproyl-L-phenylalanine as new potential antiepileptic agent could represent a good candidate to further investigations.

  18. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Science.gov (United States)

    Brzozowska, Natalia; Li, Kong M.; Wang, Xiao Suo; Booth, Jessica; Stuart, Jordyn; McGregor, Iain S.

    2016-01-01

    Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB) and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT) mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−), Bcrp knockout (Abcg2−∕−), combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕−) and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders. PMID:27257556

  19. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  20. Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy.

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; Sombati, Sompong; Elphick, Maurice R; Martin, Billy R; DeLorenzo, Robert J

    2009-09-01

    Cannabinoids have been shown to cause CB1-receptor-dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor-dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg(2+) induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg(2+) induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 h. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent downregulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg(2+) treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1-receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype.

  1. Prolonged exposure to WIN55,212-2 causes down-regulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy

    Science.gov (United States)

    Blair, Robert E.; Deshpande, Laxmikant S.; Sombati, Sompong; Elphick, Maurice R.; Martin, Billy R.; DeLorenzo, Robert J.

    2009-01-01

    Summary Cannabinoids have been shown to cause CB1-receptor dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg2+ induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 hours. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent down-regulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg2+ treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1 receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype. PMID:19540252

  2. Doenças de Dupuytren e de Ledderhose associadas ao uso crônico de anticonvulsivantes: relato de caso Dupuytren's and Ledderhose's diseases associated with chronic use of anticonvulsants: case report

    OpenAIRE

    PATRÍCIA CORAL; ALESSANDRA ZANATTA; Teive, Hélio A. G.; YLMAR CORREA NETO; EDISON MATOS NÓVAK; LINEU CÉSAR WERNECK

    1999-01-01

    Relatamos o caso de um paciente que após uso crônico de anticonvulsivantes, sem epilepsia definida, desenvolveu contraturas das aponeuroses palmar (doença de Dupuytren) e plantar (doença de Ledderhose). Discutimos as principais dessas complicações, os fatores predisponentes e sua estreita relação com o uso de anticonvulsivantes, particularmente de fenobarbital.We present the case of a patient that after chronic use of anticonvulsant drugs without proven epilepsy , developed Dupuytren's and Le...

  3. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects.

    Science.gov (United States)

    Tanno, Luciana Kase; Kerr, Daniel Shikanai; dos Santos, Bernardo; Talib, Leda Leme; Yamaguti, Célia; Rodrigues, Helcio; Gattaz, Wagner Farid; Kalil, Jorge

    2015-01-01

    Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09-14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects.

  4. Structure-property relationship of 3-(4-substituted benzyl)-1,3-diazaspiro[4.4]nonane-2,4-diones as new potentional anticonvulsant agents. An experimental and theoretical study

    Science.gov (United States)

    Lazić, Anita M.; Božić, Bojan Đ.; Vitnik, Vesna D.; Vitnik, Željko J.; Rogan, Jelena R.; Radovanović, Lidija D.; Valentić, Nataša V.; Ušćumlić, Gordana S.

    2017-01-01

    The structure-property relationship of newly synthesized 3-(4-substituted benzyl)-1,3-diazaspiro [4.4]nonane-2,4-diones was studied by experimental and calculated methods. The prepared compounds were characterized by UV-Vis, FT-IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. The crystal structure was elucidated by single-crystal X-ray diffraction. The 3-benzyl-1,3-diazaspiro[4.4]nonane-2,4-dione crystallizes in triclinic P-1 space group, with two crystallographically independent molecules in the asymmetric unit. Cyclopentane ring adopts an envelope conformation. A three-dimensional crystal packing is governed by hydrogen N-H⋯O bonds, numerous C-H⋯O/N and C-H … π interactions between neighboring molecules. Density functional theory (DFT) calculations with B3LYP and M06-2X methods using 6-311++G(d,p) basis set were performed to provide structural and spectroscopic information. Comparisons between experimental and calculated UV-Vis spectral properties suggest that the monomeric form of the investigated spirohydantoins is dominant in all used solvents. The effects of substituents on the absorption spectra of spirohydantoins are interpreted by correlation of absorption frequencies with Hammett equation. The lipophilicities of the investigated molecules were estimated by calculation of their log P values. Some of the spirohydantoins synthesized in this work, exhibit the lipophilicities comparable to the standard medicine anticonvulsant drug Phenytoin. The results obtained in this investigation afford guidelines for the preparation of new derivatives of spirohydantoin as potential anticonvulsant agents and for better understanding the structure-activity relationship.

  5. Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones

    Directory of Open Access Journals (Sweden)

    Mohamed N. Aboul-Enein

    2014-09-01

    Full Text Available Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x are reported. The intermediates 1-[(aryl(cyanomethylamino] cycloalkanecarboxamides (3a–f were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg and Ethosuximide (ED50 = 0.92 mmol/kg, respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.

  6. Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones

    Science.gov (United States)

    Aboul-Enein, Mohamed N.; El-Azzouny, Aida A.; Attia, Mohamed I.; Maklad, Yousreya A.; Aboutabl, Mona E.; Ragab, Fatma; El-Hamid, Walaa H. A. Abd

    2014-01-01

    Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones (6m–x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino]cycloalkanecarboxamides (3a–f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg) and Ethosuximide (ED50 = 0.92 mmol/kg), respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen. PMID:25250910

  7. The effect of calculus bovis cultivated by glucuronidase on anti-convulsion and anti-inflammation in mice%酶促牛黄对小鼠的抗惊厥及抗炎作用

    Institute of Scientific and Technical Information of China (English)

    许贵斌; 高允生

    2011-01-01

    Objective To observe the effects of calculus bovis cultivated by glucuronidase (CBCG )on anti-convulsion and anti-inflammation in mice, evaluate the pharmaceutical value of CBCG.Methods ( 1 )Anti-convulsion experiment.Appl ying nikethamide( NTM )-induced convulsion model and maximal electroshock convulsion ( MES ) model to observe the effect of CBCG on anti-convulsion in mice.( 2 )Anti-inflammation experiment.To apply carrageenan( CGN )-induced foot inflammation model in mice and dimethyl benzene( DMB )-induced inflammation model in mice to observe the effect of CBCG on antiinflammation.Results ( 1 )The outcome of anti-convulsion experiment showed that the CBCG and pentobarbital sodium ( PBS ) could prolong the NTM-induced convulsion latent phase in mice, raised the convulsion threshold value of maximal electroshock mice and reduce convulsion cases induced by maximal electroshock( P < 0.05, P < 0.01 ).The effect of PBS was better than CBCG( P <0.01 ),no difference was found among different CBCG groups( P >0.05 ).( 2 )The results of anti-inflammatory experiments showed that the CBCG and the aspirin( ASP ) could inhibit DMB-induced ear swell and CGN induced foot swell in mice( P < 0.05, P < 0.01 ).The CBCG had dose depend trend against DMB-induced ear swell in mice, the effect was highest in CBCG high-dose group( P < 0.05, P < 0.01 ), compared with NS gorup, ASP gorup.NCB group and CBCG group could inhibit foot swell in mice 3 ~5 h after medication( P < 0.05, P < 0.01 ), the effect was highest in NCB and CBCG high-dose group.Conclusion It proved that the CBCG had the effect of anti-convulsion and anti-inflammation in mice.%目的 观察酶促牛黄(CBCG)对小鼠的抗惊厥、抗炎作用,初步评价CBCG的药用价值.方法 (1)抗惊厥实验:分2个子实验,各取50只小鼠随机分为生理盐水组(NS组)、戊巴比妥钠组(PBS组)及CBCG高、中、低剂量组各10只,分别采用尼可刹米和最大电休克法制备小鼠惊厥

  8. 唑吡坦对小鼠镇静催眠与抗惊厥半数有效量的研究%The ED50 of zolpidem in the actions of hypnosis and anticonvulsion in rats

    Institute of Scientific and Technical Information of China (English)

    李萍; 梁煜霞

    2011-01-01

    Objective To determine the median effective dose ( ED50 ) of zolpidem in the actions of hypnosis and anticonvulsion in rats.Methods The sequential method was used to detect the ED50 of zolpidem,and then the MDA assay kit was applied to further confirm the ED50 in the action of anticonvulsion.Results The ED50 of zolpidem in the action of hypnosis was 0.084 80 mg/g and its 95%confidence interval( CI )was 0.067 61-0.103 77 mg/g,and in the action of anticonvtlsion was 0.142 57 mg/g and its 95% CI was0.127 76 - 0.156 58 mg/g.Conclusions The ED50 of zolpidem in the actions of hypnosis and anticonvulsion and their 95% confidence interval are 0.08480 mg/g and 0.067 61 - 0.103 77 mg/g,and 0.142 57 mg/g and 0.127 76 - 0.156 58 mg/g,respectively.%目的 测定唑吡坦对小鼠镇静催眠与抗回苏灵所致惊厥的半数有效量(ED50).方法 利用序贯法测定唑吡坦的半数有效量,然后利用丙二醛( MDA)试剂盒进一步确定唑吡坦抗惊厥的半数有效量.结果 唑吡坦对小鼠镇静催眠半数有效量及其相对应的95%可信区间分别为0.084 80 mg/g及0.067 61~0.103 77 mg/g;唑吡坦对小鼠抗同苏灵所致惊厥半数有效量及其相对应的95%可信区间分别为0.142 57 mg/g及0.127 76~ 0.156 58 mg/g.结论 唑吡坦对小鼠镇静催眠半数有效量和抗回苏灵所致惊厥半数有效量及其相对应的95%可信区间分别为0.08480 mg/g及0.067 61 ~ 0.103 77 mg/g和0.142 57 mg/g及0.127 76~ 0.156 58 mg/g.

  9. Study of supercritical-CO2 alcohol fluid extractions of Pinellia tuber on anticonvulsant effect%半夏超临界CO2乙醇萃取物抗惊厥作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    杨蓉; 王明正; 成银霞

    2011-01-01

    Objective: To investigate the antagonize action of supercritical-Ccfe alcohol fluid extraction of Pinellia tuber (SFE-CO2 PT) on different convulsive model and explore its mechanism of anticonvulsant action. Method: Maximal electroshock seizure (MES) and Metrazol seizure test (MET) were used to analyze the anticonvulsant effects in mice given by ig SFE-CO2 PT. Using the model of seizure rats induced by penicillin localized injected in cortex investigated the effect of SFE-CO2 PT on the convulsant behaviors and hippocampus EEC Result: SFE-CO2 PT could dose-dependently antagonize MET modle, and the dose-effect was positively correlated. It could be extended MET convulsions incubation period (P<0.01) and against the attack of MET. It had antagonism effect to the model of seizure rats induced by penicillin localized injected in cortex, extended incubation period of seizure, reduced the extent of attack, extended incubation period of epileptic discharges, reduced the frequency of epileptic waves release, reduced the maximum amplitude of the discharge, which compared with model group, all of them had significant differences (P<0.05, P<0.01). Conclusion: The SFE-CCh PT can dose-dependently antagonize MES and MET modle, meanwhile, it can against the attack of seizure rats induced by penicillin localize injected in cortex. The anticonvulsant effect is similar to Topamax modle, but compared with Topamax modle, the MES and MET modle is stronger while the seizure rats induced by penicillin localize injected in cortex is weaker.%目的:研究半夏超临界CO2乙醇萃取物对不同惊厥动物模型的对抗作用,并探讨其作用机制.方法:采用最大电休克( MES)和戊四唑惊厥模型(MET),以托吡酯(TPM)为阳性对照,观察其抗惊厥作用;建立大鼠皮层定位注射青霉素点燃模型,观察其灌胃给药对惊厥行为和脑电图的影响.结果:半夏超临界CO2萃取物对MES模型有对抗作用,且量效呈正相关

  10. Anticonvulsant Effects of Supercritical-CO2 Alcohol Fluid Extractions of Rhizoma Pinelliae%天南星超临界CO2乙醇萃取物抗惊厥作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    杨蓉; 王明正; 成银霞

    2013-01-01

    Objective To investigate the antagonize action of supercritical - CO2 alcohol fluid extraction of rhizoma pmelhae(SFE -CO2 RP) on different convulsive model and explore its mechanism of anticonvulsant action. Method Maximal electroshock seizure (MES) and Metrazol seizure test (MET) were used to analyze the anticonvulsant effects in mice treated by SFE-CO2 RP. The model of seizure rats induced by penicillin injected in cortex was used to investigate effect of SFE - CO2 RP on the convulsant behaviors and hippocampus EEG. Result SFE - CO2 RP was dose - dependently antagonize MES, and could prolong latent period (P<0.01) on MET in mice,and could also prolong the latent period on the penicillin -induced seizure and lighten the extent of seizure. At the same time,it could prolong latent period of epileptiform discharge,reduce the frequency of epileptiform discharge,and decrease the highest wave of hippocampus EEG. All above indexes were significantly difference between model group and control groups(P<0.05 or P< 0.01). Conclusion SFE -CO2 RP was dose -dependently antagonize MES and antagonize MET in mice,it also could antagonize penicillin-kindling seizure in rats. Anticonvulsant properties of SFE - CO2 RP was resemble as TPM.%目的 研究中草药天南星超临界CO2乙醇萃取物对不同惊厥动物模型的对抗作用,并探讨其作用机制.方法 采用最大电休克(MES)和戊四唑惊厥模型(MET),以托吡酯(TPM)为阳性对照,观察其抗惊厥作用;建立大鼠皮层定位注射青霉素点燃模型,观察其灌胃给药对惊厥行为和脑电图的影响.结果 天南星超临界CO2萃取物对MES模型有对抗作用,且量效呈正相关性.可延长MET惊厥潜伏期(P<0.01),对抗MET发作.对青霉素点燃模型亦产生对抗作用,可延长痫性发作潜伏期、减轻发作程度,延长痫性放电的潜伏期,减少痫波发放频率,减小放电最高波幅,与模型组比较,差异有统计学意义(P<0.05或P<0.01).结论

  11. The anti-convulsion effect of verapamil on mice model induced by pentylenetetrazol%维拉帕米抗戊四唑诱导小鼠惊厥的实验研究

    Institute of Scientific and Technical Information of China (English)

    王珣; 柳佳利; 孙浩; 李勤; 刘洋; 林熙

    2011-01-01

    Objective To study the effect of verapamil on anti-convulsion and provide a new therapeutic method for convulsion. Methods Sixty mice were divided into 3 groups as follow, the blank group, MgSO4 group and experimental group (the low, middle, high dosage of verapamil ). Pentylenetetrazol was intraperitoneally injected into mice after medication to make the model of convulsion. The occurrence time of convulsion, survival time of mice, the incidence rate of convulsion and the mortality of mice were observed. Results Compared with the blank group, either of MgSO4 and verapamil ( low,middle or high dosage) groups had longer occurrence time of convulsion. The group of MgSO4 had significantly longer survival time and lower mortality of mice ( P < 0.01 ). The groups of verapamil ( low,middle or high dosage) had also longer living time of mice ( P < 0.01 ) and the lower mortality in the low and middle dosage groups ( P <0.01 ). Conclusion The low or middle dosages of verapamil had a better curative effect of anticonvulsion in the convulsion model mice induced with pentylenetetrazol, but the high dosage of verapamil was not suitable for the anti-convulsion therapy.%目的 研究维拉帕米抗惊厥的治疗效果,为临床治疗惊厥提供新方法.方法 将实验小鼠60只分为模型对照组、硫酸镁(MgSO)组和实验组(维拉帕米低、中、高剂量组),每组12只.预先给予相应的治疗药物之后,腹腔注射戊四唑制造惊厥模型;造模成功后观察并记录小鼠的惊厥发生时间、存活时间、惊厥发生率和死亡率等.结果 与模型对照组相比,硫酸镁组和维拉帕米各剂量组惊厥发生所需时间均有所增加(P<0.01),硫酸镁组小鼠的存活时间显著延长且死亡率降低(P<0.01);维拉帕米各剂量组小鼠的存活时间延长(P<0.01),低、中剂量组死亡率明显降低(P<0.01).结论 低、中剂量维拉帕米对于戊四唑所致的惊厥模型有较好的疗效;高剂量维拉帕米不宜用于抗惊厥治疗.

  12. Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

    Science.gov (United States)

    Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

    2015-05-15

    The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

  13. Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg.%西藏长叶松树皮乙醇提取物的抗惊厥作用

    Institute of Scientific and Technical Information of China (English)

    Dhirender Kaushik; Ajay Kumar; Pawan Kaushik; Avatar C.Rana

    2012-01-01

    目的:研究西藏长叶松树皮乙醇提取物(alcoholic extract of bark of Pinus roxburghii Sarg.,AEPR)的抗惊厥作用.方法:用最大电休克和戊四唑诱发白化Wistar大鼠癫痫.最大电休克模型经由大鼠耳电极给予150mA电流刺激0.2s诱发癫痫,以后肢强直性伸展持续时间的变化作为结局指标衡量AEPR的抗惊厥作用,即后肢强直性伸展持续时间减少或停止.戊四唑模型大鼠经腹膜内注射戊四唑诱发肌阵挛性发作和阵发性抽搐,以痉挛发作的延迟衡量AEPR的抗惊厥作用.结果:在最大电休克惊厥模型中,AEPR剂量分别为300和500 mg/kg体质量,均显著减轻所有阶段的大鼠惊厥发作(P<0.01);标准对照药物苯妥英钠组用量25 mg/kg,能显著减轻屈曲阶段的发作(P<0.01),并抑制所有阶段的惊厥发作.戊四唑惊厥模型大鼠于注射戊四唑前30min分别给予AEPR 300和500mg/kg,均能显著延迟阵挛性发作(P<0.01).100 mg/kg体质量的AEPR在戊四唑诱发的癫痫模型中没有显著的抗惊厥作用;标准对照药物地西泮4 mg/kg能大幅度延迟阵挛性发作.结论:本研究提示AEPR能有效抑制普遍强直性肌阵挛和部分癫痫发作.因此,AEPR对最大电休克及戊四唑诱发的大鼠癫痫有抗惊厥作用.然而需要进一步的研究确认是AEPR中的何种成分对这种抗惊厥作用起主导作用.%OBJECTIVE:To study the anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg.(AEPR) used in Indian traditional medicine system in treating convulsion. METHODS:Anticonvulsant activity was evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in Wistar albino rats.In the MES model,150 mA current for 0.2 s was given through ear electrodes to induce convulsions in rats.The duration of tonic extension of hind limb was used as the end point,namely,prevention or decrease in the duration of hind limb extension was considered as a protective

  14. Evaluation of Anticonvulsant, Antidepressant-, and Anxiolytic-like Effects of an Aqueous Extract from Cultured Mycelia of the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Higher Basidiomycetes) in Mice.

    Science.gov (United States)

    Socala, Katarzyna; Nieoczym, Dorota; Grzywnowicz, Krzysztof; Stefaniuk, Dawid; Wlaz, Piotr

    2015-01-01

    Ganoderma lucidum is a well-known medicinal mushroom with a long history of use. This study was designed to assess the anticonvulsant potential of an aqueous extract from cultured G. lucidum mycelium in 3 acute seizure models: timed intravenous pentylenetetrazole infusion, maximal electroshock seizure threshold, and 6-Hz-induced psychomotor seizure tests in mice. Moreover, antidepressant-like and anxiolytic-like effects of G. lucidum were evaluated using the forced swim test and the elevated plus maze test in mice, respectively. No changes in seizure thresholds in the intravenous pentylenetetrazole and maximal electroshock seizure threshold tests after acute treatment with G. lucidum extract (200-600 mg/kg) was observed. However, the studied extract (100-400 mg/kg) significantly increased the threshold for psychomotor seizures in the 6-Hz seizure test. In the forced swim test, G. lucidum (100-400 mg/kg) significantly reduced the duration of immobility. No anxiolytic-like or sedative effects were reported in mice pretreated with the extract (400-600 mg/kg). G. lucidum extract (50-2400 mg/kg) did not produce toxic effects in the chimney test (motor coordination) or grip-strength test (neuromuscular strength). Further studies are required to explain the neuropharmacological effects of G. lucidum and to identify its active ingredients that may affect seizure threshold, mood, or anxiety.

  15. Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1) channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors and TRPV1 channels.

    Science.gov (United States)

    Vilela, Luciano R; Medeiros, Daniel C; de Oliveira, Antonio Carlos P; Moraes, Marcio F; Moreira, Fabricio A

    2014-10-01

    Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB1 receptors. Anandamide, however, also activates TRPV1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1 blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in inhibiting pentylenetetrazole (PTZ)-induced seizures in mice. We also investigated the contribution of CB1 activation and TRPV1 blockade to the overt effect of AA-5-HT. In the first experiment, injection of AA-5-HT (0.3-3.0 mg/kg) delayed the onset and reduced the duration of PTZ (60 mg)-induced seizures in mice. These effects were reversed by pre-treatment with the CB1 antagonist, AM251 (1.0-3.0 mg/kg). Finally, we observed that administration of the selective TRPV1 antagonist, SB366791 (0.1-1 mg/kg), did not entirely mimic AA-5-HT effects. In conclusion, AA-5-HT alleviates seizures in mice, an effect inhibited by CB1 antagonism, but not completely mimicked by TRPV1 blockage, indicating that the overall effect of AA-5-HT seems to depend mainly on CB1 receptors. This may represent a new strategy for the development of drugs against seizures, epilepsies and related syndromes.

  16. Anticonvulsive action of Pinellia Pedatisecta Schott extract prepared by ethanol-modified supercritical CO2 extraction%掌叶半夏超临界CO2乙醇萃取物的抗惊厥作用

    Institute of Scientific and Technical Information of China (English)

    陈靖京; 杨蓉; 王明正; 成银霞; 何新嘏; 马勇刚; 杨李华; 何巧燕

    2007-01-01

    AIM To investigate the anticonvulsive action of supercritical CO2 ethanol extract from Pinellia Pedatisecta Schott(SEE-CO2PP). METHODS The rat convulsive model was induced by penicillin localized injected in rat cortex. The effects of SEE-CO2PP on the latency of seizure and changes of convulsive behaviors were investigated. The latency of epileptiform discharge, and frequency and amplitude of highest wave in cortex and hippocampus were recorded by using RM6240C multichannel physiological signal collection and analysis recorder. At the same time, the contents of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly) and γ-aminobutyric acid (GABA) in hippocampus were determined with high performance liquid chromatography. RESULTS SEE-CO2PP 15 and 30 g·kg-1, ig, prolonged the latent period of seizure and weakened the extent. SEE-CO2PP also prolonged the latent period of epileptiform discharge, reduced the frequency and decreased amplitude of the highest wave in both cortex and hippocampus. Moreover, SEE-CO2PP increased the content of GABA in hippocampus, but the levels of Gly,Asp and Glu had no obvious changes. CONCLUSION SEE-CO2PP inhibits the epileptiform discharge and convulsive behaviors of convulsive model rats, which suggests SEE-CO2PP has anticonvulsive action.%目的 研究掌叶半夏超临界CO2乙醇萃取物(SEE-CO2PP)对青霉素诱发惊厥的对抗作用.方法 采用大鼠皮质局部定位注射青霉素诱发惊厥模型,研究SEE-CO2PP对惊厥发作的潜伏期以及惊厥行为变化的影响,并用RM6240C型多道生理信号采集处理仪记录皮质和海马痫性放电的潜伏期、频率和痫波最高发放波幅,同时应用高效液相色谱法测定海马谷氨酸(Glu)、天冬氨酸 (Asp)、甘氨酸(Gly)和γ-氨基丁酸(GABA)递质的含量.结果 SEE-CO2PP 15和30 g·kg-1 (ig)可延长青霉素诱发惊厥的潜伏期,并减弱发作强度.SEE-CO2PP能够延长痫性放电的潜伏期,减少痫性放电的频率,减小皮质

  17. Sedative, hypnotic and anticonvulsive effects of an adenosine analogue WS090501%腺苷类似物WS090501的镇静、催眠和抗惊厥作用

    Institute of Scientific and Technical Information of China (English)

    李伟; 张建军

    2011-01-01

    This study is to examine the sedative, hypnotic and anticonvulsive effects of an adenosine analogue, WS090501. The spontaneous locomotor activity was recorded by open field equipment, and the EEG of rats was recorded by polyphysiograph. Pentylenetetrazol (PTZ)-induced seizure model was used. The spontaneous locomotor activity was decreased by WS090501 at various doses (0.06, 0.13, and 0.25 mg·kg-1), and the decreasing rate was 28.4%, 47.1% and 61.2% respectively. Furthermore, the effect of WS090501 on spontaneous locomotor activity of mice can be antagonized by DPCPX, a selective adenosine A1R antagonist, but cannot be antagonized by SCH58261, a selective adenosine A2AR antagonist. The NREM sleep was significantly increased by WS090501 (0.05 and 0.2 mg·kg-1), and the increasing rate was 27.6% and 102.8%, respectively, at 6th hour after administration. The REM sleep decreased significantly at the higher dose. PTZ induced serious convulsion in mice. The latency of convulsion was prolonged, and the number of seizure and mortality decreased after administration of WS090501. These results show that WS090501 has potent sedative, hypnotic and anticonwlsive effects, which may be mediated through adenosine A1R.%@@ 腺苷是一种内源性的嘌呤核苷,具有广泛的生理性调节作用.腺苷类似物具有显著的镇静、催眠和抗惊厥作用,可以抑制啮齿类动物的自主活动、诱导NREM睡眠(non rapid-eye-movement sleep,非快动眼睡眠).腺苷及其类似物通过腺苷受体发挥作用.

  18. 半夏等7种中药超临界CO2萃取物抗惊厥作用比较%Comparison Study of Supercritical-CO2 Fluid Extractions of Pinellia Rhizoma on Anticonvulsant Action

    Institute of Scientific and Technical Information of China (English)

    杨蓉; 王明正; 成银霞

    2012-01-01

    Objective: To compare the anticonvulsion effect of supercritical-CO2 fluid extractions (SFE-CO2) of Bupleuri Radix , and explore their mechanism. Method: One thousand and sixty mice were randomly divided into 11 groups; RB Ⅰ group, RB Ⅱ group, RAT Ⅰ group, RAT Ⅱ group, AR Ⅱ group, UN Ⅱ group, PR Ⅱ group, SCL Ⅰ group, PS Ⅰ group, topamax group and NS group. Every group was divided into 4-6 dose groups. The maximal electroshock seizure ( MES) was used to observe the anticonvulsion effect. ED50 dose against MES was considered as the administrated dosage to observe the anticonvulsant affects in metrazol seizure test ( MET). The rat seizure model was reduced by cortex localion injection of penicillin to investigate the effect of extractions on the convulsant behaviors and hippocampus EEG (the doses were converted by ED95 of MES). Result: ①Except for RB Ⅱ and PS Ⅰ , all the other seven extractions (PR Ⅱ , UN Ⅱ , RAT Ⅰ , PR Ⅱ , SCL Ⅰ , RB Ⅰ , RAT Ⅱ ) could dose-dependently antagonize MES in mice. ②All of the seven extractions could prolong the latent period of MET in mice, and the sequence from maximum to minimum was RP Ⅱ , UN Ⅱ , RAT Ⅰ , PR Ⅱ , SCL Ⅰ , RB Ⅰ , RATⅡ . The effect of RP Ⅱ (11. 06 ±4. 32) min was better than topamax (9. 57 ± 4. 47) min. ③ The extractions with SFE-CO2 showed a faster onset and shorter duration of he anticonvulsant action than that of supercritical-CO2 alcohol fluid extractions (SAFE-CO2). ④PR Ⅱ , AR Ⅱ , UN Ⅱ , RAT Ⅰ , RAT Ⅱ and RB Ⅰ could prolong the latent period of epileptiform discharge, reduce the frequency of epileptiform discharge, and decrease the highest wave of hippocampus EEG. Conclusion: AR Ⅱ , UN Ⅱ , RAT Ⅰ , PTⅡ , SCL Ⅰ , RB Ⅰ , RATⅡ could dose-dependently antagonize MES and MET in mice; PR Ⅱ , ARⅡ , UN Ⅱ , RAT Ⅰ and RB Ⅰ could antagonize penicillin-kindling seizure in rats. PT Ⅱ may be the most effective extraction in antagonizing

  19. Anticonvulsant properties of the total alkaloid fraction of Rauvolfia ligustrina Roem. et Schult. in male mice Propriedades anticonvulsivantes da fração dos alcalóides totais de Rauvolfia ligustrina Roem. et Schult. em ratos machos

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2007-06-01

    Full Text Available Rauvolfia ligustrina Roem et. Schult (Apocynaceae, commonly known as "paratudo" and "arrebenta-boi" is a small tree found in Brazilian Northeastern. Previous studies have demonstrated depressant and anticonvulsant properties of the ethanol extract of Rauvolfia ligustrina. The aim of the present study was the determination of the lethal dose 50% (LD50 and the effects of total alkaloid fraction (TAF of the aerial parts of R. ligustrina in animal models of convulsion. It was found that the acute toxicity of TAF was 127.8 (112.5-145.2 mg/kg (i.p. in mice. TAF (20 mg/kg, ip significantly increased (p Rauvolfia ligustrina Roem. et Schult. (Apocynaceae é uma planta amplamente distribuída no Nordeste Brasileiro, rica em alcalóides indólicos, conhecida popularmente como "paratudo" e "arrebenta-boi". O presente estudo buscou avaliar a dose letal 50 % (DL50 da fração de alcalóides totais (FAT das partes aéreas da R. ligustrina e a sua possível atividade anticonvulsivantes em roedores. A FAT apresentou uma DL50, via intraperitoneal (i.p., de 127,8 (112,5-145,2 mg/kg e foi efetiva, na dose de 20 mg/kg (i.p., em proteger os animais das convulsões induzidas pelo pentilenotetrazol (PTZ e picrotoxina (PIC aumentando significativamente (p < 0,05 a latência para o aparecimento das convulsões, sendo um indicativo de um efeito anticonvulsivante.

  20. γ氨基丁酸-苯二氮(卓)受体在西番莲提取物抗大鼠惊厥中的作用%Possible role of GABAA-benzodiazepine receptor in anticonvulsant effects of Pasipay in rats

    Institute of Scientific and Technical Information of China (English)

    Marian Nassiri-Asl; Farzaneh Zamansoltani; Schwann Shariati-Rad

    2008-01-01

    Objective:To investigate the anticonvulsant effects of Pasipay,a commercially available preparation of hydro-alcoholic extract of Passiflora fncarnata in rats.Methods:The anticonvulsant effects of hydro-alcoholic extract of P.fncarnata,Pasipay.were observed by intracerebroventricuIar injection of 0.125,0.25,0.55 and 1.5 μg Pasipay.Results:Pasipay could dose-dependently affected minimal clonic seizu res and generaIized tonic-clonic seizu res induced by pentyIenetetrazole,through increment in seizu re onset significantly. Additionally,pretreatment with 5 nmol/L flumazenil could abollsh the anticonvulsant effects of Pasipay on the onset of both seizu res.Conclusion:The results indicate that Pasipay has anticonvulsant effects in the brain,possibly through positive allosteric modulation of the GABAA receptor complex via interaction at the benzodiazepiRe site.%目的:探讨γ氨基丁酸-苯二氮(卓)受体在西番莲提取物抗大鼠惊厥中的作用.方法:给大鼠脑室内分别注射0.125、0.25、0.55和1.5 μg西番莲提取物,观察其对大鼠的抗惊厥作用.结果:西番莲提取物对用戊四氮引发最小阵发性痉挛和阵发性强直性抽搐的大鼠的保护作用存在剂量依赖关系.5 nmol/L氟马西尼可阻断西番莲提取物对最小阵发性痉挛和阵发性强直性抽搐的抗惊厥作用.结论:西番莲提取物可能通过影响大脑内γ氨基丁酸-苯二氮(卓)受体的地西泮异构体结合位点来实现抗惊厥的作用.

  1. Ausências mioclônicas: estudo comparativo da potência anticonvulsivante do nitrazepam (Mogadon e do diazepam (Valium Myoclonic absences: a comparative study of the anticonvulsant potency of nitrazepan and diazepam

    Directory of Open Access Journals (Sweden)

    Michel Pierre Lison

    1969-09-01

    Full Text Available Foi comparada a potência anticonvulsivamente do nitrazepam, do diazepam e da trimetadiona em 5 pacientes com ausências mioclônicas. Os doentes receberam, além das medicações anticonculsivantes, um placebo. O teste terapêutico foi constituído por tratamentos sucessivos de 4 dias, planejados com o fim de se eliminar os possíveis efeitos residuais de uma droga sobre a outra, administrada ulteriormente. Na análise dos resultados, a comparação das médias individuais dos diversos tratamentos foi baseada no teste de Tukey. Em dois casos não houve necessidade de análise estatística para demonstrar a superioridade do nitrazepam e do diazepam sobre os demais produtos utilizados; em outros dois, a aplicação do teste de Tukey levou à mesma conclusão. No quinto caso as flutuações do número de ausências mioclônicas durante o ensaio terapêutico sugerem comportamento semelhante, embora a análise estatística individual não revele diferenças significativas. Há indícios de que o nitrazepam tem ação superior ao diazepam sobre esse tipo de crise convulsiva. A trimetadiona revelou-se superior ao placebo, porém inferior ao nitrazepam e ao diazepam. O principal inconveniente do nitrazepam e do diazepam é o de precipitar crises generalizadas tônico-clônicas.The anticonvulsant potency of nitrazepan, diazepan and trimetadiones in five patients with myoclonic absences was compared. A placebo was also used. Therapeutic tests were performed by 4-days successive treatments designed to avoid the residual effects of one drug upon the other administered afterwards. In two cases statistical analysis was not necessary for demonstration of the superiority of nitrazepan and diazepan in regard to trimetadiones; in two others the application of Tukey's test allowed this same conclusion. In the last case the numeric variations of the seizures during the therapeutic essay suggest identical conclusion allthough the statistical analysis was not

  2. Anticonvulsant effect of intranasal midazolam on maximal electroshock seizure and metrazol seizure model in rats%咪达唑仑经鼻给药在最大电休克发作及戊四唑惊厥模型的抗惊厥作用

    Institute of Scientific and Technical Information of China (English)

    田凯; 骆媛; 李万华; 隋昕; 杨军; 郑爱萍; 卫培峰; 王永安

    2015-01-01

    Objective To evaluate the anticonvulsant effect of midazolam and diazepam when administered nasally on maximal electroshock seizure and metrazol seizure threshold test models .Methods Rats were randomly divided into 7 groups:model group, low-dose, middle-dose and high-dose of midazolam nasal spray groups , diazepam nasal spray in low-dose, middle-dose and high-dose of midazolam nasal spray groups .After the establishment of the maximal electroshock seizure( MES) and metrazol seizure threshold test models ( MST) in rats, the anticonvulsant effects of different doses of midazolam and the clinically used antiepileptic drug diazepam were evaluated and compared .HE staining was used to observe the histopathological changes in the hippocampus , cortex and amygdala in rats .Results Significant anticonvulsant effects were observed on MES and MST in rats pretreated with different dosages of midazolam .In addition , the anticonvul-sant effects of midazolam were stronger than those of diazepam at the same dosage on MES and MST (P<0.05,P<0.01). Histopathological results showed that both midazolam and diazepam could effectively prevent the seizure -induced brain inju-ries, inhibit the increase of microglial cells and the inflammatory cell infiltration in the hippocampus, cortex and amygdala, and reduce the nucleus pycnosis and neuronophagia .Conclusion Midazolam has significantly anticonvulsant and neuropro-tective effects on different seizure models when administered nasally in rats .%目的:在大鼠最大电休克发作( MES)及戊四唑惊厥( MST)模型上,比较评价咪达唑仑与地西泮经鼻给药的抗惊厥作用。方法大鼠随机分为7组,分别为模型组、咪达唑仑鼻喷剂低、中、高剂量组和地西泮鼻喷剂低、中、高剂量组,每组10只。建立MES及MST模型,评价不同剂量咪达唑仑经鼻给药的抗惊厥作用,并与经典抗癫痫药物———地西泮比较,观察给药后72 h各组动物海马、

  3. Mechanism Involved in Anticonvulsant Effect of Gentianine in Rats with Recurrent Febrile Seizures%龙胆碱对反复高热惊厥大鼠的解热抗惊厥作用机制探讨

    Institute of Scientific and Technical Information of China (English)

    刘刚

    2012-01-01

    目的:探讨龙胆碱对反复高热惊厥大鼠的抗惊厥作用机制.方法:60只SD大鼠随机分为健康对照组、模型组、龙胆碱高、低剂量组,各15只.除健康对照组外,其余大鼠均按照文献方法制作高热惊厥大鼠模型.大鼠隔日诱导惊厥1次,共诱导10次,20 d.龙胆碱高、低剂量组每次惊厥后立即分别给予龙胆碱生理盐水溶液200,50 mg· kg-1,ip,模型组和健康对照组立即给予同体积生理盐水.观察各组大鼠惊厥潜伏期和惊厥持续时间;末次惊厥24 h后检测血清白细胞介素-1,6,8(IL-1,IL-6,IL-8),肿瘤坏死因子-α(TNF-α),干扰素-α(IFN-α)水平及脑组织匀浆中环磷酸腺苷(cAMP),前列腺素E2(PGE2)水平.结果:龙胆碱高、低剂量组大鼠惊厥潜伏期明显长于模型组(P<0.05);惊厥持续时间明显短于模型组(P<0.01).(P<0.05);龙胆碱高、低剂量组血清IL-1,IL-6,IL-8,TNF-α,脑组织PGE2水平明显低于模型组(P<0.05)且高剂量组低于低剂量组(P<0.05).结论:龙胆碱具有解热抗惊厥作用,其作用机制与体内细胞因子改变进而影响下丘脑PGE2水平相关.%Objective: To investigate the mechanism involved in anticonvulsant effect of gentianine in rats with recurrent febrile seizures. Method: Sixty SD rats were randomly divided into the healthy control group, model group, gentianine high-dose (200 mg·kg-1) group, gentianine low-dose (50 mg ·kg-1) group (n = 15, each). Except the health control group, all rats were induced high fever seizures according to the reference method. The rats were induced convulsion every other day, totally 10 times in 20 d. When convulsion happened, gentianine was injected (ip) immediately in the gentianine high-dose group and the low-dose group. In model group and health control group, the rats were given the same volume of normal saline. Convulsion latency and convulsion duration; serum IL-1, IL-6, IL-8 and TNF-a, IFN-a levels; brain homogenate cAMP and PGE2

  4. Recorrência da Crise Convulsiva após Terapia Anticonvulsivante com Sulfato de Magnésio em Pacientes com Eclâmpsia Recurrence of Seizures after Anticonvulsant Therapy with Magnesium Sulfate in Patients with Eclampsia

    Directory of Open Access Journals (Sweden)

    Melania Maria Ramos de Amorim

    2000-04-01

    Full Text Available Objetivos: determinar a freqüência de recorrência das crises convulsivas após tratamento com sulfato de magnésio, avaliando o tratamento adotado e o prognóstico materno. Casuística e Métodos: analisaram-se todos os casos de eclâmpsia atendidos no IMIP entre janeiro de 1995 e junho de 1998. Sulfato de magnésio e oxigenoterapia foram administrados para todas as pacientes, interrompendo-se a gravidez após estabilização do quadro clínico. Determinou-se a freqüência de complicações maternas de acordo com a presença ou não de recorrência da crise convulsiva, utilizando-se o teste chi² de associação, a um nível de significância de 5%. Resultados: doze pacientes apresentaram recorrência da eclâmpsia após sulfato de magnésio (10%, repetindo-se então metade da dose de ataque. Em 4 destas verificou-se nova recorrência, administrando-se então diazepam endovenoso. Depois do diazepam, uma paciente ainda teve crises repetidas, sendo então realizada infusão de fenitoína e, posteriormente, indução do coma barbitúrico (tionembutal. Essa paciente foi submetida a tomografia computadorizada, constatando-se hemorragia intracraniana. As complicações maternas foram significativamente mais freqüentes no grupo com recorrência: coma (16,7% versus 0,9%, acidose (50% versus 2,9%, edema agudo de pulmão (16,7% versus 2,9%, hemorragia cerebral (16,7% versus 0% e insuficiência renal aguda (16,7% versus 1,9%. Ocorreram 3 casos de morte materna no grupo com recorrência (25% e 2 no grupo sem recorrência (1,9%. Conclusões: a recorrência da crise convulsiva é pouco freqüente após uso do sulfato de magnésio (10%, porém associa-se a aumento da morbimortalidade materna, requerendo acompanhamento em UTI e realização de tomografia para exclusão de hemorragia cerebral.Purpose: to determine the frequency of recurrence of seizures after anticonvulsant therapy with magnesium sulfate and to evaluate treatment and maternal prognosis

  5. Anticonvulsant-induced downbeat nystagmus in epilepsy

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    Dongyan Wu

    2015-01-01

    Full Text Available We report data from two patients who developed reversible downbeat nystagmus (DBN while using AEDs within the therapeutic range. All previous reported cases of epilepsy with drug-induced DBN related to toxic levels of AEDs were summarized, and DBN was found mostly occurring in those using a sodium channel blocking AED. We propose that in our cases, the DBN with therapeutic AED levels may be explained by additive effects of sodium channel blockers. Adverse drug effects should be considered as a cause of DBN in people with epilepsy treated with multiple AEDs.

  6. Newer anticonvulsants: lamotrigine, topiramate and gabapentin.

    Science.gov (United States)

    Holmes, Lewis B; Hernandez-Diaz, Sonia

    2012-08-01

    BACKGROUND The second generation antiepileptic drugs (AEDs), which include lamotrigine, topiramate, and gabapentin, have been introduced during the past 20 years. Because the newer AEDs differ in their pharmacokinetics from the first generation AEDs, it is hoped that the second generation AEDs will be less teratogenic. METHODS The findings in pregnancy cohorts and case-control studies concerning lamotrigine, topiramate and gabapentin-exposed pregnancies have been analyzed. RESULTS The rate of all malformations in lamotrigine monotherapy-exposed pregnancies has been between 2.0 and 5.6%, in comparison to baseline rates of 1.1 to 3.6% in two unexposed comparison groups. Compared to reference populations, a higher risk (0.4%) of isolated oral clefts has been observed in one cohort of 1562 lamotrigine-exposed pregnancies, but the risk was lower (0.1%) in other studies. In topiramate-exposed pregnancies, the rate of all malformations has been 4.2 to 4.9%, with an increase in oral clefts with and without other anomalies. The limited information available now for gabapentin has shown no evidence of teratogenicity. Concerning other developmental effects of these drugs, young children exposed to lamotrigine in utero have shown no deficits in cognitive function. Prenatal exposure to topiramate has been associated with an elevated frequency of small size for gestational age newborns. CONCLUSIONS The information available suggests an increased risk of oral clefts in infants exposed to topiramate, and perhaps lamotrigine, early in pregnancy, and of growth retardation for topiramate-exposed infants. Larger sample sizes are needed to clarify the questions that have been raised.

  7. Thermopharmacology of anticonvulsive treatment after perinatal asphyxia

    NARCIS (Netherlands)

    van den Broek, M.P.H.

    2013-01-01

    Therapeutic hypothermia in the immediate postnatal period has been shown to be a successful strategy for neuroprotection in encephalopathic newborns in clinical trials. Due to the effect of hypothermia on physiological functions, such as heart rate and liver enzyme metabolic capacity, as well as eff

  8. Anticonvulsant-induced downbeat nystagmus in epilepsy

    Science.gov (United States)

    Wu, Dongyan; Thijs, Roland D.

    2015-01-01

    We report data from two patients who developed reversible downbeat nystagmus (DBN) while using AEDs within the therapeutic range. All previous reported cases of epilepsy with drug-induced DBN related to toxic levels of AEDs were summarized, and DBN was found mostly occurring in those using a sodium channel blocking AED. We propose that in our cases, the DBN with therapeutic AED levels may be explained by additive effects of sodium channel blockers. Adverse drug effects should be considered as a cause of DBN in people with epilepsy treated with multiple AEDs. PMID:26543808

  9. Thermopharmacology of anticonvulsive treatment after perinatal asphyxia

    OpenAIRE

    van den Broek, M.P.H.

    2013-01-01

    Therapeutic hypothermia in the immediate postnatal period has been shown to be a successful strategy for neuroprotection in encephalopathic newborns in clinical trials. Due to the effect of hypothermia on physiological functions, such as heart rate and liver enzyme metabolic capacity, as well as effects on physico-chemical properties of the drugs, such as lipophilicity, pharmacokinetic and pharmacodynamic parameters may change. Depending on the mode of action and the route of inactivation/eli...

  10. Compounding errors in 2 dogs receiving anticonvulsants.

    Science.gov (United States)

    McConkey, Sandra E; Walker, Susan; Adams, Cathy

    2012-04-01

    Two cases that involve drug compounding errors are described. One dog exhibited increased seizure activity due to a compounded, flavored phenobarbital solution that deteriorated before the expiration date provided by the compounder. The other dog developed clinical signs of hyperkalemia and bromine toxicity following a 5-fold compounding error in the concentration of potassium bromide (KBr).

  11. Anticonvulsive effect of agmatine in mice

    Institute of Scientific and Technical Information of China (English)

    Xin-QiangLu; Rui-BinSu; Xiao-LiWei; YinLiu; JinLi

    2004-01-01

    AIM: The present study was designed to examine the effect of agmatine, the decarboxylated product of L-arginine by L- arginine decarboxylase, on convulsion in the mouse maximal electroshock (MES) test and mouse glutamate-induced convulsion test. METHODS: MES convulsion and glutamate convulsion were respectively induced by an electrical stimulation

  12. Synthesis and Anticonvulsant Activity of 5-Substituted[1,2,4]triazolo[4,3-a]quinazolines%5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物的合成及抗惊厥活性

    Institute of Scientific and Technical Information of China (English)

    邓先清; 肖春瑞; 魏成喜; 全哲山

    2011-01-01

    A series of 5-substituted-[1,2,4]triazolo[4,3-α]quinazolines were synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test with intraperitoneally injected in mice. The pharmacology results showed that 5-pentyloxy-[l,2,4]triazolo-[4,3-α]quinazoline (2d) was the most potent with ED50 value of 19.7 mg/kg and protective index (PI= TD50/ED50) value of 6.2. To explain the possible mechanism of anticonvulsant activity, compound 2d was tested in several chemical induced seizures tests. The results revealed that compound 2d was effective against the seizures induced by pentylenetetrazole, isoniazid, 3-mercaptopropionic acid and thiosemicarba-zide, which suggested that the anticonvulsant effects of this series compounds were acted via increasing γ-aminobutyric acid (GABA) ergic neurotransmission and activating glutamate decarboxylase (GAD) or inhibiting α-oxoglutarate aminotransferase (GABA-T) in the brain.%合成了5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物2a~2q.利用最大电惊厥法(MES)和旋转棒法(Rotarod Test),以小鼠腹腔给药,分别测定了其抗惊厥活性和神经毒性.药理实验结果表明,化合物5-正庚氧基-1,2,4-三唑并[4,3 -a]喹唑啉(2d)的抗惊厥活性最强,其半数有效量EDso为19.7 mg/kg,保护指数PI为6.2.由化学物质诱发的抗惊厥实验结果表明,化合物2d能对抗由戊四唑、异烟肼、硫代氨基脲和3-巯基丙酸诱发的惊厥作用,推测其抗惊厥作用是通过增强γ-aminobutyric acid (GABA)神经能系统和活化谷氨酸脱羧酶或抑制GABA转氨酶而起抗惊厥作用.

  13. Investigation and Analysis of the Knowledge of Neonatal Seizure and Anticonvulsant Drugs Among Neonatologists in Sichuan Province%新生儿惊厥及抗惊厥药物认识的分析——四川地区调查

    Institute of Scientific and Technical Information of China (English)

    石晶; 陈大鹏; 熊英; 母得志

    2011-01-01

    Objective:To investigate the knowledge of neonatal seizure and anticonvulsant therapy among neonatologists in Sichuan Province. Methods: Neonatologists who attended the 2010 Annual Meeting of Sichuan Neonatology Society conpleted a self-designed questionnaire. Results: Eighty of one hundred questionnaires were returned. Most of the neonatologists chose phenobarbital and benzodiazepine as the drugs of choice. Different Anticonvulsant drug selections existed in difterent classes of hospitals. More than70%of the participants lacked basic pharmacology knowledge of anticonvulsant drugs. Most physicians chose cranial CT as the main workup for neonatal seizures. The routine EEG examination was conducted by 8% of the physicians and a neurologic consultation was only prefenred by 7% of the participants. Conclusions: Most of the participants lack basic pharmacology knowledge. It is necessary to strengthen nultidisciplinary collaboration and medical staff training in the workup and management of neonatal seizures.%目的:了解四川省新生儿科医师对新生儿惊厥和抗惊厥药物的认识情况.方法:自行设计问卷对参加2010年四川省新生儿学组年会的新生儿临床医师进行匿名问卷调查.结果:问卷有效回收率80%.苯巴比妥钠和地西泮是受访医师新生儿抗惊厥治疗首选药物,不同等级医院药物使用情况有一定差异;70%以上的医师缺乏基本的抗惊厥药物药理学知识;大多数受访者在临床工作中使用头颅CT作为新生儿惊厥病因的主要检查手段,8%临床医师经常对新生儿惊厥患儿进行脑电监测,7%新生儿科医师经常同神经科医师讨论新生儿惊厥治疗方案.结论:受访的大多数新生儿科医师缺乏必要的抗惊厥药物药理学知识,在新生儿惊厥治疗中有必要加强多科协作和人员培训.

  14. 静脉麻醉药抑制利多卡因致大鼠惊厥作用的比较%Comparisons of anticonvulsant action of intravenous anesthetics against lidocaine-induced convulsion in rats

    Institute of Scientific and Technical Information of China (English)

    王春平; 张山; 刘红梅; 韩倩

    2012-01-01

    Objective To compare the anticonvulsant action of midazolam, propofol, etomidate and thiopental on lidocaine-induced convulsion in rats. Methods Thirty-six male Wistar rats weighing (250±20) g were equally randomized into 6 groups: (1) control group (group C); (2) lidocaine group (group L: lidocaine 4 mg ·k1 ·min-1 until convulsion); (3) lidocaine and propofol group (group P, lidocaine and propofol 12.5 mg/kg), (4) lidocaine and etomidate group (group E: lidocaine and etomidate 1. 85 mg/kg) , (5) lidocaine and midazolam group (group M: lidocaine and midazolam 0. 65 mg/kg) , (6) lidocaine and thiopental group (group T: lidocaine and thiopental 30. 85 mg/kg). Animals were decapitated 2 hours after convulsion and the brains were removed. One side of hippocampus was obtained for detecting expressions of c-fos protein. The other side was obtained to measure the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (N()S). Results The c-fos positive cells, the concentration of NO and the activity of NOS increased significantly in group L compared with group C (P<0. 05). The c-fos positive cells, the NO concentration and the activity of NO.S were significantly lower in groups P, M, E and T compared with group L (P<0. 05), and especially in groups M and T. Conclusion Propofol, midazolam, etomidate and thiopental can inhibit lidocaine-induced convulsion in rats and it is more significant by midazolam and thiopental.%目的 比较静脉麻醉药丙泊酚、依托咪酯、咪达唑仑及硫喷妥钠拮抗利多卡因致大鼠惊厥的作用.方法 雄性Wistar大鼠36只,体重(250±20)g,随机均分为六组:空白对照组(C组)、利多卡因组(L组:利多卡因4 mg· kg- 1·min-1)、利多卡因+丙泊酚组(P组:利多卡因+丙泊酚12.5ng/kg)、利多卡因+依托咪酯组(E组:利多卡因+依托咪酯1.85mg/kg)、利多卡因+咪达唑仑组(M组:利多卡因+咪达唑仑0.65mg/kg)和利多卡因+硫喷妥钠组(T组:

  15. 半夏生物总碱和钩藤生物总碱抗小鼠、大鼠惊厥的协同作用%Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

    Institute of Scientific and Technical Information of China (English)

    成银霞; 王明正; 陈靖京; 杨蓉; 何欣嘏; 马永刚; 杨李华; 张明升

    2007-01-01

    目的 研究半夏生物总碱(PTA)和钩藤生物总碱(UTA)抗惊厥的协同作用,并探讨其相互作用机制.方法 采用小鼠最大电休克惊厥试验和急性毒性试验检测PTA和UTA单用和三种比例(1:1,1:4,4:1)配伍的抗惊厥作用及毒性效应,并采用bliss's法分别计算它们的ED50和LD50.用等效线法评价其协同作用并计算各组配伍的受益指数(BD.制备大鼠运动皮层定位注射青霉素惊厥模型,同时采用高效液相色谱法(HPLC)测定海马区癫痫相关递质Glu、Asp、Gly、GABA的含量.结果 半夏、钩藤生物总碱4:1配伍的抗惊厥作用呈现协同,而毒性呈现相互拮抗,是PTA和UTA合用的最佳比例.而两药1:4和1:1比例配伍尽管在最大电休克惊厥试验中抗惊厥作用呈现协同,但是在毒性试验中毒性效应却呈现相加.PTA和UTA单用和4:1合用,均可明显减少海马Glu的水平,增加GABA的水平,且4:1合用组的GABA水平要比两单药组高.但对Asp、Gly无明显影响.结论 PTA和UTA以4:1合用时抗癫痫效应协同、毒性拮抗.两药合用的抗惊厥作用机制可能与其同时降低Glu能神经的兴奋性,并协同提高GABA能神经功能有关.%Aim To investigate the synergistic effect of the combination of pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA), and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1:4,1:1, 4:1, were evaluated in maximal electroshock (MES)-induced seizures and acute toxicity test in mice. Respective ED50 and LD5o were calculated with Bliss's method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices (BI) for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high

  16. 贝那替秦对最大电休克发作模型和戊四氮惊厥发作阈模型小鼠的抗惊厥作用%Anticonvulsant effects of benactyzine on maximal electroshock seizure and pentetrazole seizure threshold test model mice

    Institute of Scientific and Technical Information of China (English)

    陈小飞; 李建雄; 王永安

    2011-01-01

    目的 评价贝那替秦等抗胆碱药在不同惊厥模型的抗惊厥疗效,探讨其可能的作用机制.方法 通过ig给予贝那替秦2~40 mg·kg-1记录最大电休克发作模型( MES)及戊四氮惊厥发作阈模型(MST)模型小鼠的未出现惊厥数.制备新生Wistar小鼠海马神经元细胞,加入贝那替秦1~100 μmol·L-1,MTT检测细胞存活率.结果 贝那替秦2~40 mg·kg-1在MES模型未出现惊厥数为2/10~7/10,在MST模型上未出现惊厥数为1/10~9/10均明显高于模型组(P<0.05,P<0.01),2个模型的ED50分别为12.2(4.7~53.6)mg·kg-1和12.5(7.0~25.9)mg·kg-1.贝那替秦1~100 μmol·L-1能明显对抗N-甲基-D-天冬氨酸(NMDA)对海马神经元的损伤作用,细胞存活率明显增加(P<0.05).结论 贝那替秦在MES及MST惊厥模型均具明显抗惊厥作用,其作用机制可能与其对NMDA受体的拮抗作用有关.%OBJECTIVE To evaluate the anticonvulsant effect of benactyzine and other anticholinergic drugs on different seizure models and investigate their anti-seizure mechanism. METHODS Benactyzine 2 -40 mg· kg -1 were given ig to mice. The number of mice without convulsant appearance was recorded in the maximal electroshock seizure (MES) and pentetrazole (Metrazol)seizure threshold test (MST) model. Benactyzine 1 -100 μmol·L-1 was added to primary cultured hippocampus neurons, and the cell survival was detected by MTT assay. RESULTS The number of mice without convulsant appearance was 2/10 -7/10 in the MES model vs 1/10 -9/10 in MST model. The ED50 of benactyzine in MES model was 12.2 (4.7 - 53.6) mg· kg-1 vs 12.5 (7.5 -25.9)mg·kg-1 in the MST model. The cell survival in benactyzine 1 -100 μmol·L-1 group was significantly higher than that of N-methyl-D-aspartic acid ( NMDA ) model group ( P < 0.05 ).CONCLUSION Benactyzine shows significant anti-seizure effect on both MES and MST. The anticonvulsant mechanism might be related to its antagonism against NMDA receptors.

  17. Anticonvulsant activity of novel 1-(morpholinomethyl-3-substituted isatin derivatives

    Directory of Open Access Journals (Sweden)

    Govindaraj Saravanan

    2014-06-01

    Full Text Available A variety of novel isatin derivatives 5a–5j and 6a–6j were synthesized and characterized by spectroscopic means and elemental analysis. The title compounds were investigated for antiepileptic activity using MES and scPTZ seizures tests. Neurotoxicity study was performed by the rotorod test. The relationship between the functional group variation and the biological activity of the evaluated compounds was discussed. Among the synthesized analogs, the most active one was 6f that revealed protection in MES at a dose of 30 mg/kg (i.p. after 0.5 h and 4 h. This molecule also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h and 300 mg/kg (4 h.

  18. Epilepsy, Anticonvulsants and Cognitive Functions in School Students.

    Science.gov (United States)

    Keister, Douglas Charles

    Research is reviewed on epilepsy and findings summarized in terms of intelligence, relationship between etiology and intelligence, seizure frequency, age of onset, duration, premorbid intelligence, and specific psychological defects, electroencephalography (EEG) and IQ, and learning. Among findings noted are that the widespread belief among…

  19. Anticonvulsant, Anxiolytic, and Sedative Activities of Verbena officinalis

    Science.gov (United States)

    Khan, Abdul Waheed; Khan, Arif-ullah; Ahmed, Touqeer

    2016-01-01

    We describe different neuropharmacological effects of Verbena officinalis crude extract (Vo.Cr). Pentylenetetrazole (PTZ)-induced seizures, elevated plus maze, light–dark box (LDB), open field and thiopental-induced sleeping test models were employed to evaluate Vo.Cr actions in mice. Vo.Cr dose-dependently (100–500 mg/Kg) delayed onset time of myoclonic jerks and tonic-clonic seizures, while decreased duration of tonic-clonic seizures (P diazepam. In open field test, Vo.Cr decreased number of ambulations and rearings frequencies, while increased the number of central squares crossings. In thiopental-induced sleeping test, Vo.Cr (50–300 mg/Kg) decreased onset time of sleep, while increased the duration of sleep (P anxiety, and insomnia. PMID:28066246

  20. Anticonvulsant therapy in brain-tumor related epilepsy

    Directory of Open Access Journals (Sweden)

    Fröscher Walter

    2016-06-01

    Full Text Available Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

  1. The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents

    DEFF Research Database (Denmark)

    Stas, Jeroen I; Bocksteins, Elke; Jensen, Camilla S

    2016-01-01

    μM retigabine concentrations had 'off-target' effects on KV2.1 channels which have recently been implicated in apoptosis. Clinical retigabine concentrations (0.3-3 μM) inhibited KV2.1 channel function upon prolonged exposure. The suppression of the KV2.1 conductance was only partially reversible....... Our results identified KV2.1 as a new molecular target for retigabine, thus giving a potential explanation for retigabine's neuroprotective properties....

  2. Pharmacokinetic equivalence study of two formulations of the anticonvulsant pregabalin

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2015-04-01

    Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Ratih Sofia Ika Putri,2 Vincent Angga Gunawan,2 Fenny Ong,1 Liana W Susanto,1 Dwi Nofiarny11Dexa Laboratories of Biomolecular Sciences, Cikarang, West Java, Indonesia; 2PT Equilab International Bioavailability and Bioequivalence Laboratory, Jakarta, IndonesiaPurpose: The present study was conducted to evaluate whether the bioavailability of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to the reference formulation.Methods: This was a randomized, open-label, two-period, two-sequence, and crossover study under fasting condition, with a 1-week washout period. Plasma concentrations of pregabalin from 20 subjects were determined by using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS detection method. Pharmacokinetic parameters assessed in this study were: area under the plasma concentration–time curve from time zero to last observed quantifiable concentration (AUC0–t, area under the plasma concentration–time curve from time zero to infinity (AUC0–∞, maximum plasma concentration (Cmax, time to maximum plasma concentration (tmax, and terminal half-life (t1/2. The 90% confidence intervals (CIs for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and Cmax parameters; while tmax difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t1/2 difference was analyzed using Student's paired t-test.Results: The mean (standard deviation [SD] AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the test formulation were 27,845.86 (4,508.27 ng·h/mL, 28,311.70 (4,790.55 ng·h/mL, 3,999.71 (801.52 ng/mL, and 5.66 (1.20 hours, respectively; while the mean (SD AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the reference formulation were 27,398.12 (4,266.28 ng·h/mL, 27,904.24 (4,507.31 ng·h/mL, 3,849.50 (814.50 ng/mL, and 5.87 (1.25 hours, respectively. The median (range tmax of pregabalin from the test formulation and reference formulation was 1.00 (0.67–2.00 hours and 1.00 (0.67–3.00 hours, respectively. The 90% CIs for the geometric mean ratios of test formulation/reference formulation for pregabalin were 101.54% (98.75%–104.41% for AUC0–t, 101.35% (98.66%–104.11% for AUC0–∞, and 104.19% (98.75%–109.93% for Cmax.Conclusion: The study concluded that the two formulations of pregabalin capsules studied were bioequivalent.Keywords: antiepileptic, bioavailability, bioequivalence, generic product

  3. Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Joppolo Di Ventimiglia, Samuele

    2003-01-01

    Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them...

  4. Ação do anticonvulsivante isolado e associado ao midazolam como medicação pré-anestésica sobre o índice bispectral (BIS em pacientes com paralisa cerebral Acción del antiepiléptico aislado y asociado al midazolam como medicación preanestésica sobre el índice bispectral (BIS en pacientes con parálisis cerebral Effect of isolated anticonvulsant drug use and associated to midazolam as pre-anesthetic medication on the bispectral index (BIS in patients with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Verônica Vieira da Costa

    2010-06-01

    -anesthetic drug on the BIS of patients with CP undergoing chronic treatment with anticonvulsant agents. METHOD: Three groups of patients were assessed: CP without anticonvulsant treatment, CP undergoing treatment with anticonvulsant and a group with no disease and no medication use (control group. On the day before the surgery, with the patients conscious and in dorsal decubitus, the BIS monitor was placed and the basal BIS values were recorded. On the following day, 40 minutes before the surgery, the patients received 0.6 mg.kg-1 of midazolam orally. Before the start of the anesthetic procedure, the same procedure for BIS recording was carried out after midazolam administration. RESULTS: A total of 107 patients were studied - 39 patients from the Control Group (CG and 68 with a diagnosis of CP. Among these, 17 used anticonvulsant drugs. Regarding the mean BIS value after the midazolam administration, there was no difference between patients from the CG and those in the CP group that did not take anticonvulsant drugs, whereas the ones who took anticonvulsants exhibited a difference (p = 0.003. The possibility of decrease in the BIS after midazolam use increases according to the number of anticonvulsant drugs used by the patient. CONCLUSIONS: The chronic use of anticonvulsants associated to oral midazolam as pre-anesthetic medication can lead to the decrease in the BIS values, which configures deep level of hypnosis.

  5. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  6. Voltage-gated sodium channels: pharmaceutical targets via anticonvulsants to treat epileptic syndromes.

    Science.gov (United States)

    Abdelsayed, Mena; Sokolov, Stanislav

    2013-01-01

    Epilepsy is a brain disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels, Nav1.1 and Nav1.2. The effects of antiepileptic drugs (AEDs) as effective therapies for epilepsy have been characterized by extensive research. Most of the classic AEDs targeting Nav share a common mechanism of action by stabilizing the channel's fast-inactivated state. In contrast, novel AEDs, such as lacosamide, stabilize the slow-inactivated state in neuronal Nav1.1 and Nav1.7 isoforms. This paper reviews the different mechanisms by which this stabilization occurs to determine new methods for treatment.

  7. Evaluating of the Anticonvulsant Gabapentin against Nerve Agent-Induced Seizures in a Guinea Pig Model

    Science.gov (United States)

    2010-07-01

    this drug or similar compounds of this class (e.g., pregabalin, Lyrica®) would be considered as a replacement for, or a supplement to, diazepam or...L.W., Talbot, B.G., Anderson, D.R. Relationship between reversible acetylcholinesterase inhibition and efficacy against soman lethality. Life Science...treatment of nerve agent seizures: anticholinergics vs diazepam in soman- intoxicated guinea pigs. Epilepsy Research, 2000, 38:1-14. McDonough, J.H

  8. Novel Anticonvulsant Analogs of Dextromethorphan: Improved Efficacy, Potency, Duration and Side-Effect Profile

    Science.gov (United States)

    1994-02-01

    1991) and psychotomimetic reac- programs of Tallarida and Murray (1987). tions (Dodds, 1967; Fleming, 1986) associated with high-dose For convulsant...regression and parallelism was accom- 100 plished by using procedures 5 and 6 from Tallarida and Murray (1987). Flurothyl seizure thresholds were compared by... TALLARIDA . R_ J. AND M’URRAY, R. B.: Manual of Pharmacologic Calculations induced by glucose deprivation in vitro. Brain Ras. 446: 144-148, 198 with Computer

  9. Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals

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    Musa Mumammad Aliyu

    2014-04-01

    Conclusions: These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.

  10. Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent-Induced Seizures

    Science.gov (United States)

    2002-01-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...development of them as a field treatments would be impractical (e.g., clonidine, huprazine, ivermectin ; worked over narrow dose range and only as

  11. Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro and in vivo seizure models.

    Directory of Open Access Journals (Sweden)

    Mohamed G Qaddoumi

    Full Text Available Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models. In vitro seizures were induced in the hippocampal slice chemically (zero Mg2+ buffer and picrotoxin and electrically using patterned high frequency stimulation (HFS of afferents. In vivo seizures were induced in rats using the 6 Hz and the maximal electroshock models. AK6 (10 µM and E249 (10 µM depressed the amplitude of population spikes recorded in area CA1 of the hippocampus by -50.5±4.3% and -40.1±3.1% respectively, with partial recovery after washout. In the zero Mg2+ model, AK6 (10 µM depressed multiple population spiking (mPS by -59.3±6.9% and spontaneous bursts (SBs by -65.9±7.2% and in the picrotoxin-model by -43.3±7.2% and -50.0±8.3%, respectively. Likewise, E249 (10 µM depressed the zero-Mg2+-induced mPS by -48.8±9.5% and SBs by -55.8±15.5%, and in the picrotoxin model by -37.1±5.5% and -56.5±11.4%, respectively. They both suppressed post-HFS induced afterdischarges and SBs. AK6 and E249 dose-dependently protected rats in maximal electroshock and 6 Hz models of in vivo seizures after 30 min pretreatment. Their level of protection in both models was similar to that obtained with phenytoin Finally, while AK6 had no effect on locomotion in rats, phenytoin significantly decreased locomotion. AK6 and E249, suppressed in vitro and in vivo seizures to a similar extent. Their in vivo activities are comparable with but not superior to phenytoin. The most efficacious, AK6 produced no locomotor suppression while phenytoin did. Thus, AK6 and E249 may be excellent candidates for further investigation as potential agents for the treatment of epilepsy syndromes with possibly less CNS side effects.

  12. Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

    Science.gov (United States)

    2014-12-01

    AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Organophosphate (OP... poisoning can result in status epilepticus (SE), which can become pharmacoresistant if treatment is delayed. Virtually no data exist on OP-induced...are needed to characterize models of P7 and P14 DFP-induced SE. 15. SUBJECT TERMS Status Epilepticus, seizure, organophosphate , DFP, pediatric

  13. Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

    Directory of Open Access Journals (Sweden)

    D.D. Damasceno

    2012-11-01

    Full Text Available Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR and in normal Wistar rats (N = 6/group. The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively. The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40 and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40 for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.

  14. Anticonvulsants: choices and costs. Based on a presentation by Nina Graves, PharmD, FCCP.

    Science.gov (United States)

    1998-09-01

    Epilepsy is not a single disease but a constellation of different syndromes and different seizure types. Consequently, establishing a diagnosis on which to base therapy can be complicated. The most commonly used antiepileptic drugs (AEDs) fall into two broad categories: the older AEDs introduced between 1912 and 1973 and the newer AEDs introduced since 1993. The older AEDs have many off-label uses, whereas the newer AEDs, with the exception of gabapentin and lamotrigine, are used exclusively for the treatment of epilepsy. All AEDs are associated to varying degrees with adverse effects on the central nervous system, gastrointestinal tract, blood, liver, and skin. The older AEDs are less expensive than the newer AEDs, but because the newer agents are available in both titration and maintenance-dose strengths, cost savings are possible. Use of the high-strength dose of a newer AED represents a huge cost saving per day compared with using the low-strength dose. Further savings can be realized in the managed care arena if pharmacists are involved in getting patients onto high-strength tablets as quickly as possible.

  15. The Anticonvulsant Effects of SR 57227 on Pentylenetetrazole-Induced Seizure in Mice

    OpenAIRE

    Li, Bingjin; Wang, Liang; Sun, Zhihui; Zhou, Yang; Shao, Dongyuan; Zhao, Jing; Song, Yunong; Lv, Jiayin; Dong, Xue; Liu, Changhong; Wang, Pu; ZHANG, XINGYI; Cui, Ranji

    2014-01-01

    Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were al...

  16. Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

    Science.gov (United States)

    2007-01-01

    Organophosphorous nerve agents-induced cological Basis of Therapeutics, 10th ed. (Hardman JG, Limbird LE, and ( Gilman seizures and efficacy of atropine...us.army.mil Taylor P (2001) Anticholinesterase agents, in Goodman and Gilman’s The Pharrna-

  17. Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

    Energy Technology Data Exchange (ETDEWEB)

    Damasceno, D.D. [Departamento de Desenvolvimento Educacional,Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais, Barbacena, MG (Brazil); Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doretto, M.C.; Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-07-20

    Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.

  18. Specific safety and tolerability considerations in the use of anticonvulsant medications in children

    Directory of Open Access Journals (Sweden)

    Crepeau A

    2012-06-01

    Full Text Available Amy Z Crepeau,1 Brian D Moseley,2 Elaine C Wirrell31Division of Epilepsy, Department of Neurology, Mayo Clinic, 2Department of Neurology, Mayo Clinic, 3Divisions of Epilepsy and Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USAAbstract: Epilepsy is one of the most common neurological disorders in the pediatric age range, and the majority of affected children can be safely and effectively treated with antiepileptic medication. While there are many antiepileptic agents on the market, specific drugs may be more efficacious for certain seizure types or electroclinical syndromes. Furthermore, certain adverse effects are more common with specific classes of medication. Additionally patient-specific factors, such as age, race, other medical conditions, or concurrent medication use may result in higher rates of side effects or altered efficacy. Significant developmental changes in gastric absorption, protein binding, hepatic metabolism, and renal clearance are seen over the pediatric age range, which impact pharmacokinetics. Such changes must be considered to determine optimal dosing and dosing intervals for children at specific ages. Furthermore, approximately one third of children require polytherapy for seizure control, and many more take concurrent medications for other conditions. In such children, drug–drug interactions must be considered to minimize adverse effects and improve efficacy. This review will address issues of antiepileptic drug efficacy, tolerability and ease of use, pharmacokinetics, and drug–drug interactions in the pediatric age range.Keywords: antiepileptic drugs, drug–drug interactions, pharmacokinetics

  19. Predicting parental anticonvulsant medication compliance using the theory of reasoned action.

    Science.gov (United States)

    Austin, J K

    1989-04-01

    One approach to better understanding compliance behavior is the use of the theory of reasoned action. In this article, the theory of reasoned action is used to predict the compliance behavior of 29 parents of children with epilespy. In support of the theory, behavioral intention was found to significantly predict (p less than 0.01) parental medicine-giving behavior. Contrary to the results predicted by the theory, parents' attitudes toward giving the medication correlated with a significant amount of variance in medicine-giving behavior beyond that accounted for by behavioral intention.

  20. Crystal structure of 1,3-dimethyl-3-phenylpyrrolidine-2,5-dione: a clinically used anticonvulsant

    Directory of Open Access Journals (Sweden)

    Carlos Ordonez

    2014-09-01

    Full Text Available In the title compound, C12H13NO2, the five-membered ring has an envelope conformation; the disubstituted C atom lies out of the mean plane through the four other ring atoms (r.m.s. deviation = 0.0038 Å by 0.1877 (18 Å. The plane of the phenyl substituent is practically perpendicular to that of the planar part of the five-membered ring, with a dihedral angle of 87.01 (5°. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming inversion dimers. The dimers are linked by further C—H...O hydrogen bonds, as well as carbonyl–carbonyl attractive interactions [O...C = 3.2879 (19 Å], forming a three-dimensional framework structure.

  1. Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats.

    Science.gov (United States)

    Sadek, Bassem; Saad, Ali; Latacz, Gniewomir; Kuder, Kamil; Olejarz, Agnieszka; Karcz, Tadeusz; Stark, Holger; Kieć-Kononowicz, Katarzyna

    2016-01-01

    A series of twelve novel non-imidazole-based ligands (3-14) was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R). The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3-14) tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES)-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally), whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ) model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR) but not the brain-penetrant H2R antagonist zolantidine (ZOL), demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR) model. Moreover, the experimental and in silico estimation of properties such as metabolism was performed for five selected test compounds. Also, lipophilicity using planar reversed-phase thin-layer chromatography method was included for better understanding of the molecular properties of the tested compounds. Additionally, the absorption, distribution, metabolism, and elimination and toxicity parameters were evaluated for the most promising compounds 2, 4, 6, 7, and 14 utilizing in vitro methods. These interesting results highlight the potential of H3R ligands as new antiepileptic drugs or as adjuvants to available epilepsy medications.

  2. Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs III. A Preliminary Report: Parent Interviews about Drug Treatment.

    Science.gov (United States)

    Gadow, Kenneth D.

    Interviewed were 115 parents of children receiving medication for hyperactivity, convulsive disorders, or other reasons. Parents received a Children's Medication Chart (CMC) which contained life size pictures of 69 different products to aid parents in identifying medication. The telephone interview covered such aspects as frequency of…

  3. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol.

    Science.gov (United States)

    Schulpen, Sjors H W; de Jong, Esther; de la Fonteyne, Liset J J; de Klerk, Arja; Piersma, Aldert H

    2015-04-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecular interaction of compounds with the neural differentiation process. Within the 11-day differentiation protocol of the assay, embryonic stem cells lost their pluripotency, evidenced by the reduced expression of stem cell markers Pou5F1 and Nanog. Moreover, stem cells differentiated into neural cells, with morphologically visible neural structures together with increased expression of neural differentiation-related genes such as βIII-tubulin, Map2, Neurogin1, Mapt and Reelin. Valproic acid (VPA) and carbamazepine (CBZ) exposure during hESTn differentiation led to concentration-dependent reduced expression of βIII-tubulin, Neurogin1 and Reelin. In parallel VPA caused an increased gene expression of Map2 and Mapt which is possibly related to the neural protective effect of VPA. These findings illustrate the added value of gene expression analysis for detecting compound specific effects in hESTn. Our findings were in line with and could explain effects observed in animal studies. This study demonstrates the potential of this assay protocol for mechanistic analysis of specific compound-induced inhibition of human neural cell differentiation.

  4. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; de Jong, Esther; de la Fonteyne, Liset J. J.; de Klerk, Arja; Piersma, Aldert H.

    2015-01-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecu

  5. The Acute and Chronic Effects of the Novel Anticonvulsant Lacosamide in an Experimental Model of Status Epilepticus

    OpenAIRE

    Wasterlain, Claude G; Stöhr, Thomas; Matagne, Alain

    2011-01-01

    The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE.

  6. THE SIGNIFICANCE OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA OF THE RAT DURING SEIZURES AND ANTICONVULSANT TREATMENTS

    NARCIS (Netherlands)

    SAYIN, U; TIMMERMAN, W; WESTERINK, BHC

    1995-01-01

    The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold inc

  7. [The role of the substantia nigra in the anticonvulsive and antiaggressive effects of diazepam during pharmacological kindling].

    Science.gov (United States)

    Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Makul'kin, R F

    1990-01-01

    The seizure activity was investigated on the model of pharmacological kindling which was induced by repeated picrotoxin injections in the subthreshold dose, after the tryptic fragment of T5 protein-human diazepam binding inhibitor (DBI) (10 micrograms) injection into a reticular part of substantia nigra. An increase in the seizure reaction and suppression of the antiseizure diazepam action were observed. Intranigral DBI injection induced no change in a threshold of "attacks" in rats which were induced through electric shocks delivered to animals with an electrode floor and no changes in antiaggressive diazepam action were observed under such conditions.

  8. Potentiation of anticonvulsant activity of phenytoin by calcium channel blockers (verapamil and amlodipine against maximal electroshock seizures in rats

    Directory of Open Access Journals (Sweden)

    Monika Sharma

    2014-08-01

    Conclusions: From the present investigation, it may be concluded that the dose of DPH may be reduced in an antiepileptic individual who is on verapamil and amlodipine therapy. [Int J Basic Clin Pharmacol 2014; 3(4.000: 608-610

  9. Evaluation and Comparison of Anticonvulsant Activity of Telmisartan and Olmesartan in Experimentally Induced Animal Models of Epilepsy

    Science.gov (United States)

    V H, Pushpa; R N, Suresha; M K, Jayanthi; V, Ashwini; P S, Vaibhavi

    2014-01-01

    Background: Epilepsy is one common neurological disorder requiring newer targets and newer drugs for its efficient management. In the recent days brain renin angiotensin system has gained immense importance because of its involvement in seizure regulation. Objective: To evaluate and compare antiepileptic activity of different doses olmesartan and telmisartan on MES and PTZ induced seizure models. Materials and Methods: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: Control ( Distilled Water- 10ml/kg), Standard – Sodium valproate (40mg/kg), O1 – Olmesartan (2.5mg/kg), O2 – Olmesartan (5mg/kg), T1 - Telmisartan (5mg/kg), T2 – Telmisartan (10mg/kg). After 1hour of administration of control , test and standard drugs (orally), convulsions were induced by administering PTZ (70mg/kg – i.p.) in PTZ model. Seizure latency was the parameter recorded. In MES model, suppression of tonic hind limb extension was taken as measure of efficacy. Result: The results were analysed by one-way-ANOVA followed by Bonferroni’s multiple comparison test. In MES test, dose dependently olmesartan and telmisartan significantly reduced the duration of tonic hindlimb extension in comparison to control (p<0.05). T2 – 9 + 0.89secs significantly reduced the tonic hind limb extension compared to other test groups (p<0.05). The percentage inhibition of seizure was T2-44.3%, O2-28.2%, T1-17.5%, O1- 12.3% respectively. In PTZ test, dose dependently olmesartan and telmisartan produced significant increase in seizure latency (p<0.05). T2 - 206.6+9.83secs significantly increased seizure latency compared to other test groups (p<0.05). Percentage protection from seizure is T2-52.6%, O2- 45.13%, T1- 37.5%, O1- 38.4% respectively. Conclusion: AT1 receptor antagonist, telmisartan and olmesartan in a dose dependent manner showed increase in antiepileptic activity. Temisartan at higher dose produced significant antiepileptic activity in comparison to olmesartan. PMID:25478368

  10. Autoradiographic Distribution and Applied Pharmacological Characteristics of Dextromethorphan and Related Antitissue/Anticonvulsant Drugs and Novel Analogs.

    Science.gov (United States)

    1994-10-01

    4.4 4 Cerebellum: Purkinje cell layer 64.0 ± 10.5 4 granular cell layer 46.1 ± 7.5 4 molecular cell layer 23.4 ± 1.1 4 TABLE 2: Autoradiographical...43.0 ± 7.4 5 granular cell layer 23.0 ± 7.3 5 molecular cell layer 14.0 ± 4.4 5 j cu 4) A k- , -.- ’ A 1 *9 ,𔃻 I A .. ’, * 3A .. . .A *4...nucleus solitary tract 36.8 ± 7.1 5 reticular nucleus 36.6 ± 7.6 5 Cerebellum: Purkinje cell layer 48.6 ± 10.3 5 granular cell layer 28.6 ± 7.8 5 molecular

  11. Evaluation of the anticonvulsant activity of the essential oil of Myrothamnus moschatus in convulsion induced by pentylenetetrazole and picrotoxin

    Directory of Open Access Journals (Sweden)

    Emmanuel Randrianarivo

    2016-06-01

    Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.

  12. Anticonvulsant hypersensitivity syndrome:a report of 5 cases%抗癫(癎)药过敏综合征5例报告

    Institute of Scientific and Technical Information of China (English)

    王涛; 侯坤; 范春燕; 孙红霞

    2006-01-01

    @@ 抗癫(癎)药过敏综合征(antiepileptic drug hypersensitive syndrome,AHS)是一种抗癫(癎)药所致的临床副反应综合征,主要表现为发热、皮疹和内脏损害.国内对此综合征的诊断、治疗、远期随访曾有详细报道.现将我院1993年2月至2003年3月收治的5例患儿临床资料分析如下.

  13. The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review.

    Science.gov (United States)

    Dols, Annemiek; Sienaert, Pascal; van Gerven, Heleen; Schouws, Sigfried; Stevens, Anja; Kupka, Ralph; Stek, Max L

    2013-11-01

    Side effects are among the most frequent reasons preventing patients from taking their medication. Although the management of side effects is an important issue in clinical practice, particularly in patients with physical comorbidities, research on clinical management of side effects is rather scattered. The aim of this article was to provide an overview on the prevalence and management of various side effects of mood-stabilizing drugs. In December 2012, we carried out a PubMed search for publications reporting side effects in patients with bipolar disorder. Naturalistic studies describing the prevalence of side effects in treatment with mood stabilizers are sparse. We describe the prevalence of neurological, gastrointestinal, metabolic, thyroid, dermatological, nephrogenic, cognitive, sexual, hematological, hepatogenic, and teratogenic side effects of lithium, valproate, carbamazepine, and lamotrigine and discuss their clinical management. There are specific strategies that aim at reducing side effects, but, to date, studies on the efficacy of these interventions are lacking. With age, the renal elimination and hepatic metabolism of drugs reduce and comedication and somatic comorbidity increase, making elderly patients particularly susceptible to side effects. Most side effects can be managed by striving for the lowest possible dose without losing efficacy by lowering the dose below the therapeutic window. Specific measurements to limit certain side effects are available and may ameliorate treatment adherence.

  14. Design and synthesis of the anticonvulsant derivatives of norcantharidin%去甲斑蝥素抗惊厥衍生物的设计与合成

    Institute of Scientific and Technical Information of China (English)

    李泳秀; 孙晓飞; 魏初铨

    2009-01-01

    癫痫是一种由多种原因引起的脑部神经元群阵发性异常放电所致的植物神经功能异常的疾病,以反复发作性、短暂性、通常为刻板性的中枢神经系统功能失常为特征的综合征。世界上大约4千万到5千万人遭受癫痫的折磨,其中80%在发展中国家。我国癫痫患者人数已升至900万之多,且每年有将近40万的新发病人。

  15. Imidazenil: A Low Efficacy Agonist at α1- but High Efficacy at α5-GABAA Receptors Fail to Show Anticonvulsant Cross Tolerance to Diazepam or Zolpidem

    OpenAIRE

    2008-01-01

    Whereas advances in the molecular biology of GABAA receptor complex using knock-out and knock-in mice have been valuable in unveiling the structure, composition, receptor assembly, and several functions of different GABAA receptor subtypes, the mechanism(s) underlying benzodiazepine (BZ) tolerance and withdrawal remain poorly understood. Studies using specific GABAA receptor subunit knock-in mice suggest that tolerance to sedative action of diazepam requires long-term activation of α1 and α5 ...

  16. The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice.

    Science.gov (United States)

    Shirazi-zand, Zahra; Ahmad-Molaei, Leila; Motamedi, Fereshteh; Naderi, Nima

    2013-07-01

    Cannabidiol is a nonpsychoactive member of phytocannabinoids that produces various pharmacological effects that are not mediated through putative CB1/CB2 cannabinoid receptors and their related effectors. In this study, we examined the effect of the i.c.v. administration of potassium BK channel blocker paxilline alone and in combination with cannabidiol in protection against pentylenetetrazol (PTZ)- and maximal electroshock (MES)-induced seizure in mice. In the PTZ-induced seizure model, i.c.v. administration of cannabidiol caused a significant increase in seizure threshold compared with the control group. Moreover, while i.c.v. administration of various doses of paxilline did not produce significant change in the PTZ-induced seizure threshold in mice, coadministration of cannabidiol and paxilline attenuated the antiseizure effect of cannabidiol in PTZ-induced tonic seizures. In the MES model of seizure, both cannabidiol and paxilline per se produced significant increase in percent protection against electroshock-induced seizure. However, coadministration of cannabidiol and paxilline did not produce significant interaction in their antiseizure effect in the MES test. The results of the present study showed a protective effect of cannabidiol in both PTZ and MES models of seizure. These results suggested a BK channel-mediated antiseizure action of cannabidiol in PTZ model of seizure. However, such an interaction might not exist in MES-induced convulsion.

  17. THE EFFECT OF ANTICONVULSANT DRUGS (PHENOBARBITAL AND VALPROIC ACID ON THE SERUM LEVEL OF CHOLESTEROL, TRIGLYCERIDE, LIPOPROTEIN AND LIVER ENZYMES IN CONVULSIVE CHILDREN

    Directory of Open Access Journals (Sweden)

    Mohammad Reza SALEHIOMRAN

    2010-12-01

    Full Text Available ObjectiveStudies on the effect of various antiepileptic drugs on serum lipids show contradictory results. We aimed to find the effect of Phenobarbital and Sodium Valproate monotherapy on serum lipid profile and liver function tests in epileptic children.Materials & MethodsThis cohort study was conducted in Amirkola Children Hospital. One hundred and ten children with epilepsy were included in this study. Children with hepatic or renal disease, those receiving medications which could alter liver function tests or serum lipid profile were excluded from the study. Patients were allocated into two groups. The first group, including 63 patients, received Phenobarbital and the second group, including 47 patients, received Sodium Valproate, both in divided doses. A venous blood sample was collected after overnight fasting to evaluate serum triglyceride, total cholesterol, LDL, HDL, and liver function tests. Data was analyzed with SPSS version 17.ResultsIn children receiving Phenobarbital, total cholesterol, LDL, HDL, ALP, SGOT and SGPT increased significantly after treatment, but TG level showed no significant changes. In children receiving Sodium Valproate, HDL, ALP, SGOT, SGPT significantly increased after treatment but there were no statistically significant changes in total cholesterol, LDL and TG. In our study, the plasma levels of LPa elevated significantly after treatment with Phenobarbital and Sodium Valproate (P Value=0.0001. This increase was more significant in patients receiving Sodium Valproate.ConclusionOur results suggested a need for monitoring serum total cholesterol, HDL, LDL, and TG levels in patients receiving Phenobarbital and Valproic Acid.Keywords: Seizure, Phenobarbital, Sodium Valproate.

  18. The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. V. Lack of seasonal influences on amygdala kindling in rats.

    Science.gov (United States)

    Wlaź, P; Löscher, W

    1993-10-01

    Previous studies have suggested that seizure models may be affected by seasonal rhythms, even under controlled environmental conditions. In the present experiments in rats with chronically implanted electrodes in the basolateral amygdala, kindling was initiated at different seasons of the year over a period of 3 years. In a total of 109 animals, the following parameters were determined: the threshold for induction of amygdaloid afterdischarges prior to kindling (pre-kindling ADT), the number of daily amygdaloid stimulations to fully kindled (stage 5) seizures, and the post-kindling ADT. No seasonal influences were found with respect to rate of kindling development and post-kindling ADT. In contrast, pre-kindling ADTs appeared to be higher in spring than in other seasons, which, however, could not be reproduced in another spring. Thus, the data do not indicate that seasonal rhythms affect the kindling model of epilepsy.

  19. Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents Avaliação anticonvulsivante de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, em roedores

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2010-03-01

    Full Text Available The Aim of this study was to evaluated the effects of the ethanol extract of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, roots (EER in animal models of epilepsy. The EER increased the latency for convulsions significantly different from control (pO presente estudo buscou avaliar os efeitos do extrato etanólico das raízes de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, (EER e sua possível atividade anticonvulsivante em roedores. No teste das convulsões induzidas pelo pentilenotetrazol (PTZ os animais tratados com EER, 250 mg/kg (i.p., apresentaram aumento significativo (p<0,05 da latência para o aparecimento das convulsões (328,9±47,5 quando comparado aos do grupo controle (103,5±21,8 e reduziu o número de óbitos. Esse efeito foi bloqueado pela administração do flumazenil. O EER produziu aumento significativo (p<0,05 na latência nos testes da picrotoxina (PIC e da estricnina (EST, nas maiores doses. No modelo do eletrochoque auricular o EER não produziu alterações significativas em nenhum dos parâmetros avaliados. Entretanto, no modelo do abrasamento induzido pelo PTZ, a administração com o EER produziu um efeito protetor, atenuando de forma significativa (p<0,05 o desenvolvimento e a severidade das crises convulsivas. Os resultados, sugerem que o EER induziu efeito anticonvulsivante em roedores e que o sistema GABAérgico pode estar envolvido nessa resposta.

  20. Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress.

    Science.gov (United States)

    Tawfik, Mona K

    2011-12-01

    Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.

  1. Pre-hospital midazolam for benzodiazepine-treated seizures before and after the Rapid Anticonvulsant Medication Prior to Arrival Trial: A national observational cohort study

    Science.gov (United States)

    Silbergleit, Robert

    2017-01-01

    Background Implementation of evidence-based treatment for pre-hospital status epilepticus can improve outcomes. We hypothesized that publication of a pivotal pre-hospital clinical trial (RAMPART), demonstrating superiority of intramuscular midazolam over intravenous lorazepam, altered the national utilization rates of midazolam for pre-hospital benzodiazepine-treated seizures, while upholding its safety and efficacy outside the trial setting. Methods and findings This is a retrospective, observational cohort study of pre-hospital patient encounters throughout the United States in the National Emergency Medicine Services Information System database, from January 2010 through December 2014. We compared the rates and odds of midazolam use as first-line treatment among all adult and pediatric benzodiazepine-treated seizures before and after RAMPART publication (February 2012). Secondary analyses were conducted for rates of airway interventions and rescue therapy, as proxies for safety and efficacy of seizure termination. 156,539 benzodiazepine-treated seizures were identified. Midazolam use increased from 26.1% in January 2010 to 61.7% in December 2014 (difference +35.6%, 95% CI, 32.7%-38.4%). The annual rate of midazolam adoption increased significantly from 5.9% per year to 8.9% per year after the publication of RAMPART (difference +3.0% per year; 95%CI, 1.6%-4.5% per year; adjusted OR 1.24; 95%CI, 1.17–1.32). Overall frequency of rescue therapy and airway interventions changed little after the publication of RAMPART. Conclusions These data are consistent with effective, ongoing, but incomplete clinical translation of the RAMPART results. The effects of the trial, however, cannot be isolated. The study was limited by broad inclusion of all benzodiazepine-treated seizures as well as a lack of information on route of drug of administration. The safety and effectiveness of midazolam for benzodiazepine-treated seizures in prehospital clinical practice appear consistent with trial data, which should encourage continuing increases in utilization. PMID:28306741

  2. Anticonvulsive Activity in Audiogenic DBA/2 Mice of 1,4-Benzodiazepines and 1,5-Benzodiazepines with Different Activities at Cerebellar Granule Cell GABAA Receptors.

    Science.gov (United States)

    Gatta, Elena; Cupello, Aroldo; Di Braccio, Mario; Grossi, Giancarlo; Robello, Mauro; Scicchitano, Francesca; Russo, Emilio; De Sarro, Giovambattista

    2016-12-01

    Herein, we tested in a model of generalized reflex epilepsy in mice different 1,4-benzodiazepines and 1,5-benzodiazepines with agonistic activity at the GABAA receptor population contributing to the peak component of the chloride current elicited by GABA in cerebellar granule cells (CGCs) in culture. The substances have all higher lipophilia than clobazam, an antiepileptic drug well known and used in human therapy. This ensures that they all can pass relatively easily the blood-brain barrier (BBB). The benzodiazepines were administered intraperitoneally (i.p.) and tested for their activity against sound-induced tonic and clonic seizures in a genetic model of experimental epilepsy, the DBA/2 mouse. Our data demonstrates an interesting inverse correlation between the ED50s and the efficacy (E %) of the drugs in increasing the peak chloride current elicited by GABA in cerebellar granule cells in culture. There is indication of the existence of a threshold of E % above which the increase of ED50 with increasing E % becomes linear. This is statistically significant for the clonic phase, whereas it is at the limit of significance for the tonic one. A possible interpretation of these results is that in this epilepsy model, projections from the cerebellum exert a convulsion prevention activity.

  3. Rufinamide

    Science.gov (United States)

    ... Rufinamide is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the ... 5 years of age and older who took anticonvulsants such as rufinamide during clinical studies were found ...

  4. Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder

    DEFF Research Database (Denmark)

    Nielsen, Ditte Dencker; Bak-Jensen, Henriette Husum

    2010-01-01

    Retigabine is a novel compound with anticonvulsant efficacy. Preclinical studies have indicated that the compound, like other anticonvulsants may also have antimanic efficacy. Bipolar disorder is characterized by episodes of depression and mania, which show a progressively faster recurrence...

  5. Sandhoff Disease

    Science.gov (United States)

    ... nutrition and hydration and keeping the airway open. Anticonvulsants may initially control seizures. × Treatment There is no ... nutrition and hydration and keeping the airway open. Anticonvulsants may initially control seizures. View Full Treatment Information ...

  6. Vigabatrin

    Science.gov (United States)

    ... Vigabatrin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like vigabatrin to treat various conditions during clinical ...

  7. Gabapentin

    Science.gov (United States)

    ... Gabapentin is in a class of medications called anticonvulsants. Gabapentin treats seizures by decreasing abnormal excitement in ... older (about 1 in 500 people) who took anticonvulsants such as gabapentin to treat various conditions during ...

  8. Phenytoin

    Science.gov (United States)

    ... Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as phenytoin to treat various conditions during ...

  9. Brivaracetam Injection

    Science.gov (United States)

    ... older. Brivaracetam in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like brivaracetam injection to treat various conditions during ...

  10. Levetiracetam

    Science.gov (United States)

    ... Levetiracetam is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the ... older (about 1 in 500 people) who took anticonvulsants such as levetiracetam to treat various conditions during ...

  11. Methsuximide

    Science.gov (United States)

    ... Methsuximide is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as methsuximide to treat various conditions during ...

  12. Pregabalin

    Science.gov (United States)

    ... Pregabalin is in a class of medications called anticonvulsants. It works by decreasing the number of pain ... older (about 1 in 500 people) who took anticonvulsants such as pregabalin to treat various conditions during ...

  13. Neuroacanthocytosis

    Science.gov (United States)

    ... Seizures may be treated with a variety of anticonvulsants, and antidepressants may also be appropriate for some ... Seizures may be treated with a variety of anticonvulsants, and antidepressants may also be appropriate for some ...

  14. Encephalopathy

    Science.gov (United States)

    ... provide specific instructions for proper care and treatment. Anticonvulsants may be prescribed to reduce or halt any ... provide specific instructions for proper care and treatment. Anticonvulsants may be prescribed to reduce or halt any ...

  15. Ezogabine

    Science.gov (United States)

    ... Ezogabine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as ezogabine to treat various conditions during ...

  16. Valproic Acid

    Science.gov (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  17. Motor Neuron Diseases

    Science.gov (United States)

    ... glycopyrrolate and atropine to treat excessive saliva; and anticonvulsants and nonsteroidal anti-inflammatory drugs to relieve pain. ... glycopyrrolate and atropine to treat excessive saliva; and anticonvulsants and nonsteroidal anti-inflammatory drugs to relieve pain. ...

  18. Oxcarbazepine

    Science.gov (United States)

    ... Oxcarbazepine is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as oxcarbazepine to treat various conditions during ...

  19. Lacosamide Injection

    Science.gov (United States)

    ... injection is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like lacosamide injection to treat various conditions during ...

  20. Ethosuximide

    Science.gov (United States)

    ... Ethosuximide is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as ethosuximide to treat various conditions during ...

  1. Examples of Dietary Supplement Interactions

    Science.gov (United States)

    ... levels, which can decrease effectiveness of the medicines.Anticonvulsants. May affect chemicals in the brain, which can decrease effectiveness of the anticonvulsants.Trazodone. May affect chemicals in the brain, which ...

  2. Zonisamide

    Science.gov (United States)

    ... Zonisamide is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as zonisamide to treat various conditions during ...

  3. Felbamate

    Science.gov (United States)

    ... Felbamate is in a class of medications called anticonvulsants. It works by decreasing abnormal activity in the ... older (about 1 in 500 people) who took anticonvulsants such as felbamate to treat various conditions during ...

  4. Brivaracetam

    Science.gov (United States)

    ... Brivaracetam is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like brivaracetam to treat various conditions during clinical ...

  5. Primidone

    Science.gov (United States)

    ... Primidone is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as primidone to treat various conditions during ...

  6. Tiagabine

    Science.gov (United States)

    ... Tiagabine is in a class of medications called anticonvulsants. It is not known exactly how tiagabine works, ... mention any of the following: amiodarone (Cordarone, Pacerone);anticonvulsants such as carbamazepine (Tegretol), ethosuximide (Zarontin), gabapentin (Neurontin), ...

  7. Meningitis and Encephalitis

    Science.gov (United States)

    ... for viral encephalitis or other severe viral infections.Anticonvulsants are used to prevent or treat seizures. Corticosteroidd ... for viral encephalitis or other severe viral infections.Anticonvulsants are used to prevent or treat seizures. Corticosteroidd ...

  8. Perampanel

    Science.gov (United States)

    ... Perampanel is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like perampanel to treat various conditions during clinical ...

  9. Eslicarbazepine

    Science.gov (United States)

    ... Eslicarbazepine is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the ... older (about 1 in 500 people) who took anticonvulsants such as eslicarbazepine to treat various conditions during ...

  10. Topiramate

    Science.gov (United States)

    ... Topiramate is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the ... older (about 1 in 500 people) who took anticonvulsants such as topiramate to treat various conditions during ...

  11. Landau-Kleffner Syndrome

    Science.gov (United States)

    ... for LKS usually consists of medications, such as anticonvulsants and corticosteroids, and speech therapy, which should be ... for LKS usually consists of medications, such as anticonvulsants and corticosteroids, and speech therapy, which should be ...

  12. Carbamazepine

    Science.gov (United States)

    ... Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as carbamazepine to treat various conditions during ...

  13. Lamotrigine

    Science.gov (United States)

    ... Lamotrigine is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as lamotrigine to treat various conditions during ...

  14. Lacosamide

    Science.gov (United States)

    ... Lacosamide is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like lacosamide to treat various conditions during clinical ...

  15. Early Post Traumatic Seizures in Military Personnel Result in Long Term Disability

    Science.gov (United States)

    2013-10-01

    adjustment of anticonvulsants and duration of anticonvulsants based on the presence of seizures and/or inter-ictal epileptiform activity will be...discontinuation of anticonvulsants will be followed for all subjects (see detailed methods). A standardized MRI protocol will be applied to all subjects...function. This impairment may be related to a seizure-related induced secondary injury or from the side effects of anticonvulsant treatment. Stopping

  16. Effect of Long Gu on Sedation、Hypnosis and Anticonvulsion in Mice%龙骨对小鼠镇静与抗惊厥作用的初步研究

    Institute of Scientific and Technical Information of China (English)

    李光华; 周旭; 贺弋; 库宝善

    2002-01-01

    目的:探讨龙骨镇静与抗惊厥作用.方法:采用开野法、戊巴比妥钠镇静催眠法和戊四唑致惊厥法.结果:龙骨水煎液可显著地减少小鼠的自主活动,缩短其入睡时间和延长睡眠时间,延长戊四唑所致小鼠惊厥的潜伏期和减少惊厥发生的百分率(P<0.01).结论:龙骨确有很强的镇静与抗惊厥作用.

  17. Selective GABA transporter inhibitors tiagabine and EF1502 exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABA(A) receptor agonist gaboxadol

    DEFF Research Database (Denmark)

    Madsen, Karsten Kirkegaard; Ebert, Bjarke; Clausen, Rasmus Prætorius

    2011-01-01

    Modulation of the extracellular levels of GABA via inhibition of the synaptic GABA transporter GAT1 by the clinically effective and selective GAT1 inhibitor tiagabine [(R)-N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid; Gabitril] has proven to be an effective treatment strategy for focal...

  18. Synthesis of γ-Aminobutyric Acid Isothiocyanate Conjugated Norcantharidin and Substituted Anilin and Anticonvulsant Activity%4-去甲斑蝥酰亚胺基丁酰苯硫脲的合成及抗惊厥活性

    Institute of Scientific and Technical Information of China (English)

    魏初铨; 李泳秀; 孙晓飞

    2010-01-01

    合成了11种γ-氨基丁酸异硫氰酯偶联去甲斑蝥素与取代苯胺目标化合物,其结构经IR、 ~1H NMR和HR-MS测试技术确证.抗惊厥活性初步测定表明,化合物Ⅱ_2、Ⅱ_3和Ⅱ_8显示了较强的抗惊厥活性.

  19. Study Progress of 1, 2, 4-triazole Anticonvulsant Compounds%含有1,2,4-三氮唑环抗癫痫化合物研究进展

    Institute of Scientific and Technical Information of China (English)

    崔丽京; 卞明; 包宏; 于丽君

    2013-01-01

    1, 2, 4-triazole ring is considered as a biologically important active heterocyclic structure that possesses al-most many biological activities. This paper reviews the research progress of many anti-epileptic compounds possess this structure.%1,2,4-三氮唑环是一类很重要的杂环结构,其表现出的多种生物活性使得该类化合物的研究不断涌现。笔者就具有该结构的抗癫痫化合物研究进展进行综述。

  20. Nursing of 16 children with Stevens-Johnson syndrome caused by anticonvulsants%16例抗癫痫药物致Stevens-Johnson综合征患儿的护理

    Institute of Scientific and Technical Information of China (English)

    唐汇群; 何彩英; 鄢爱梅

    2008-01-01

    报告了16倒因口服抗癫痫药物致Stevens-Johnson综合征的护理方法.Stevens-Johnson综合征的护理目的 是防止受损皮肤黏膜感染,促进受损皮肤和黏膜修复.主要护理措施包括:严格执行消毒隔离措施、皮肤五官的保护、控制体温、药物的安全应用、饮食护理、心理护理等.16例Stevens-Johnson综合征忘儿未发生严重并发症,全部痊愈出院,平均疗程21d.

  1. An Experimental Study on the Anticonvulsive Action of the Extraction from Radix Bupleuri%柴胡萃取成分抗惊厥作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘燕; 廖卫平; 高玫梅

    2001-01-01

    目的:研究柴胡萃取物的抗惊厥作用.方法:采用超临界CO2萃取法得到柴胡皂甙部分及挥发油部分,用戊四唑阈值发作模型(MSTT)及最大电休克模型(MES)来研究其抗惊厥作用.结果:柴胡挥发油300mg/kg与柴胡皂甙150mg/kg配伍组有较强的抗戊四唑惊厥作用(P<0.01);挥发油300mg/kg,皂甙150mg/kg与冰片36.4mg/kg配伍后则有显著的抗MES作用(P<0.001).结论:柴胡挥发油部分与柴胡皂甙部分合理配伍后有较强的抗惊厥作用.

  2. L-pGlu-(2-propyl)-L-His-L-ProNH₂ attenuates 4-aminopyridine-induced epileptiform activity and sodium current: a possible action of new thyrotropin-releasing hormone analog for its anticonvulsant potential.

    Science.gov (United States)

    Sah, N; Rajput, S K; Singh, J N; Meena, C L; Jain, R; Sikdar, S K; Sharma, S S

    2011-12-29

    L-PGlu-(2-propyl)-L-His-L-ProNH₂ (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg⁺²-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg⁺² (2.10±0.47 Hz) as compared with nACSF (0.12±0.08 Hz). A significant decrease in mean firing frequency (0.61±0.22 Hz), mean frequency of epileptiform events (0.03±0.02 Hz vs. 0.22±0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54±1.21 Hz vs. 8.16±0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246±19 mV ms⁻¹ vs. 297±18 mV ms⁻¹ of 4-AP+0 Mg) and increase (1.332±0.018 ms vs. 1.292±0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 μM) depressed sodium current (15±0.5%, 50±2.6%, and 75±0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly.

  3. Anticonvulsiva bij agressie, angststoornissen, psychotische stoornissen en alcohol- en cocaïneonttrekkingsverschijnselen

    NARCIS (Netherlands)

    Barth-Van Veldhuizen, H.G.J.; Reinders, C.; Loonen, A.J.M.; Nolen, W.A.

    2003-01-01

    BACKGROUND: There is an increasing interest in the treatment of psychiatric symptoms with anticonvulsants, especially in the treatment of refractory patients. It is questionable whether or not the efficacy of anticonvulsants as psychotropic drugs is sufficiently verified. AIM: To examine the efficac

  4. Chorea

    Science.gov (United States)

    ... levodopa, anti-convulsants, and anti-psychotics) metabolic and endocrine disorders, and vascular incidents. × Definition Chorea is an abnormal ... levodopa, anti-convulsants, and anti-psychotics) metabolic and endocrine disorders, and vascular incidents. View Full Definition Treatment There ...

  5. Tiagabine in treatment refractory bipolar disorder : a clinical case series

    NARCIS (Netherlands)

    Suppes, T; Chisholm, KA; Dhavale, D; Frye, MA; Atshuler, LL; McElroy, SL; Keck, PE; Nolen, WA; Kupka, R; Denicoff, KD; Leverich, GS; Rush, AJ; Post, RM

    2002-01-01

    Objectives: Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the gamma-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant

  6. 2-取代酰基-1-烷基-5-苯基-3-吡唑烷酮类化合物的合成及抗惊厥作用的研究%Study on the Synthesis and the Anticonvulsant Activity of 2-Substituted Acyl-1-alkyl-5-phenyl-3-pyrazolidinones

    Institute of Scientific and Technical Information of China (English)

    全哲山; 朴虎日; 李玉花

    2001-01-01

    本文合成了11个2-取代酰基-1-烷基-5-苯基-3-吡唑烷酮类衍生物,并进行了抗惊厥作用药理实验.药理实验结果表明,11个化合物中3个化合物具有较强的抗惊厥活性.

  7. 1,3,4,5-四氢-7-烷氧基-2H-1-苯并氮杂(卓)-2-酮的合成及生物活性%Synthesis and Anticonvulsant Activity of 1,3,4,5-tetrahydro-7-alkoxy -2H-1-benzazepin-2-one

    Institute of Scientific and Technical Information of China (English)

    金大成; 张威; 朴凤玉

    2010-01-01

    合成了一系列1,3,4,5-四氢-7-烷氧基-2H-1-苯并氮杂(卓)-2-酮衍生物.采用最大电惊厥实验测定化合物的抗惊厥活性,其中的1,3,4,5-四氢-7-丁氧基-2H-1-苯并氮杂(卓)-2-酮(4b)具有较强的抗惊厥活性,ED_(50)为52.8 mg/kg,TD_(50)为246.2mg/kg,PI为4.7.

  8. Effect of anticonvulsant gabapentin on visceral nociception and its relationship with amino acid neurotransmitters released from spinal cord%抗惊厥药加巴喷丁抑制内脏疼痛的作用及其与脊髓氨基酸递质释放的关系

    Institute of Scientific and Technical Information of China (English)

    冯艺; 崔明磊; William D. WILLIS

    2003-01-01

    目的:研究抗惊厥药加巴喷丁对内脏疼痛的作用及其对脑脊液中氨基酸释放的影响.方法:48只SD大鼠分别随机接受腹腔内注射生理盐水、加巴喷丁50 mg*kg-1、加巴喷丁100 mg*kg-1或加巴喷丁200 mg*kg-1,40 min后经腹腔内注射0.6%(体积分数)醋酸4 ml*kg-1诱发内脏疼痛.观察并比较不同组大鼠1 h内醋酸诱发腹肌收缩次数.另选择两组大鼠在戊巴比妥麻醉下,通过置入蛛网膜下腔的微透析管采集脑脊液,应用高压液相法测定腹腔内注射0.6%醋酸后透析脑脊液中氨基酸浓度的变化,包括谷氨酸、天门冬氨酸、丝氨酸、甘氨酸、谷氨酰胺.比较加巴喷丁预处理(100 mg*kg-1)对内脏疼痛后脑脊液中氨基酸释放的影响.结果: 加巴喷丁以剂量相关方式减低内脏疼痛行为学改变.腹腔内注射醋酸后,脑脊液透析液中谷氨酸、天门冬氨酸和丝氨酸浓度明显增加,而谷胺酰胺和甘氨酸增加差异无显著性.加巴喷丁预治疗可明显抑制醋酸引起的脑脊液中谷氨酸、天门冬氨酸和丝氨酸浓度增高.结论:加巴喷丁可有效抑制醋酸诱发的内脏疼痛,其抑制作用可能与抑制伤害性刺激诱发的中枢兴奋性氨基酸释放有关.

  9. 低剂量纳洛酮对氯胺酮抗局麻药致惊厥作用的影响%The effect of low-dose naloxone on the anticonvulsant action of ketamine on local anaesthetics-induced convulsion

    Institute of Scientific and Technical Information of China (English)

    徐小林; 周纯; 石春雷; 陈银宝; 戴体俊; 黄水平

    2009-01-01

    目的 观察氯胺酮(ketamine,KT)对罗哌卡因(ropivacaine,R)、布比卡因(bupivacaine,B)、利多卡因(lidocaine,L)致惊厥作用的影响,以及低剂量纳洛酮(naloxone, NL)对此效应的影响.方法 腹腔注射低剂量纳洛酮(10 ng/kg), 5 min后腹腔注射氯胺酮(10 mg/kg),再过5 min后腹腔注射致惊厥剂量的罗哌卡因、布比卡因、利多卡因(分别为89.5 mg/kg、100 mg/kg、60 mg/kg),观察小鼠惊厥的持续时间、惊厥次数和惊厥率.并用序贯法测定腹腔注射氯胺酮(20 mg/kg)5 min后,罗哌卡因、布比卡因、利多卡因致惊厥ED50.结果 氯胺酮(20 mg/kg)能增加罗哌卡因、布比卡因、利多卡因致惊厥的ED50(P0.05).结论 在本实验条件下,氯胺酮能够增强罗哌卡因、布比卡因、利多卡因致惊厥作用,低剂量纳洛酮能够增强氯胺酮抗利多卡因惊厥的作用.

  10. Antipsicóticos, anticonvulsivantes, antiadrenérgicos e outras drogas: o que fazer quando o transtorno do estresse pós-traumático não responde aos inibidores seletivos da recaptação da serotonina? Antipsychotics, anticonvulsants, antiadrenergics and other drugs: what to do when posttraumatic stress disorder does not respond to selective serotonin reuptake inhibitors?

    Directory of Open Access Journals (Sweden)

    William Berger

    2007-10-01

    Full Text Available OBJETIVOS: Nesta revisão narrativa, o objetivo foi descrever as opções farmacológicas para o tratamento do transtorno de estresse pós-traumático nos casos de intolerância, resistência, refratariedade ou impossibilidade de utilizar antidepressivos, especialmente inibidores seletivos da recaptação da serotonina. MÉTODO: Consulta às bases de dados ISI Web of Science e PubMed em busca de estudos originais sobre o tratamento farmacológico do transtorno de estresse pós-traumático em diferentes cenários clínicos. RESULTADOS: Evidências preliminares apontam para a utilidade de drogas como a risperidona, a olanzapina, a lamotrigina e o prazosin como estratégias para o cenário clínico em tela. A escolha do medicamento de segunda linha deve levar em conta não só os sintomas, como também as comorbidades, os tratamentos prévios, as interações farmacológicas, os efeitos colaterais e as condições físicas do paciente. CONCLUSÕES: Futuros ensaios clínicos randomizados ainda são necessários para estabelecer com clareza alternativas farmacológicas aos antidepressivos para o tratamento do transtorno de estresse pós-traumático.OBJECTIVES: In this narrative review, we aimed to describe different pharmacological strategies for the treatment of patients with post-traumatic stress disorder who display different levels of intolerance, resistance, refractoriness, or who are unable to take to antidepressants, especially serotonin reuptake inhibitors. METHOD: We searched the ISI web of science and the PubMed for original studies focusing in the treatment of PTSD in different clinical scenarios. RESULTS: Preliminary evidence pointed towards the efficacy of drugs such as risperidone, olanzapine, lamotrigine and prazosin as strategies to be employed in the above mentioned clinical scenarios. The choice of a specific "second line" drug should take into account not only symptoms, but also pattern of comorbidities, previous response to other treatments, pharmacological interactions, side-effects, and patient's physical conditions. CONCLUSIONS: Future randomized controlled trials should be performed in order to unveil which drugs should be prescribed in the absence of adequate treatment and response to serotonin reuptake inhibitors.

  11. 加巴喷丁胶囊治疗疱疹后神经痛的多中心临床观察%A multicenter, randomized, double-blind, placebo-controlled, parallel design study on the efficacy and safety of gabapentin, an anticonvulsant drug in the treatment of postherpetic neuralgia

    Institute of Scientific and Technical Information of China (English)

    顾菊林; 温海; 刘训荃; 郑志忠; 顾军; 于浩

    2009-01-01

    目的 观察加巴喷丁治疗疱疹后神经痛的临床疗效和安全性.方法 多中心、随机双盲、安慰剂对照、平行设计临床试验.疱疹后神经痛患者随机分为治疗组和对照组,两组患者分别口服加巴喷丁胶囊1800 mg/d或安慰剂胶囊,总共接受6周的药物治疗.于治疗前及治疗后第1、3、6周各随访1次,进行疗效和安全性评价.以视觉模拟评分法进行疱疹后神经痛的疼痛评分作为主要观察指标,以5点严重程度评分方法进行睡眠质量评分作为次要观察指标.结果 4个中心共人选141例疱疹后神经痛患者,125例完成试验,其中试验组66例,对照组59例.与用药前相比,用药后1周、3周和6周时,两组在疼痛严重程度、睡眠质量方面均有不同程度改善;试验组在用药后1周、3周改善更为明显.用药后第1周和第3周试验组的有效率分别为29.58%和57.75%,对照组分别为13.04%和40.58%,试验组高于对照组,两组比较,差异均有统计学意义(X2CMH分别为5.94,4.12,P<0.05).加巴喷丁有较好的耐受性,不良反应主要表现为头晕、头昏、嗜睡和转氨酶升高等.结论 加巴喷丁胶囊治疗疱疹后神经痛,能改善患者疼痛严重程度和睡眠质量,不良反应发生率低.%Objective To observe the clinical efficacy and safety of gahapentin in the treatment of postherpetic neuralgia. Methods A multicenter, randomized, double-blind, placebo-controlled, parallel design, 6-week study was performed. Patients with postherpetic neuralgia were recruited into this study and randomly divided into two groups to receive gabapentin or placebo 1800 mg daily in three divided doses with a forced titration schedule, respectively. The primary efficacy measure was change in the pain score based on a visual analogue scale from baseline to the final week of therapy, and secondary measure was the improvement in sleep quality scored on a 5-point severity scale. Efficacy and safety evaluation was performed at baseline, and 1, 3, and 6 weeks atter the treatment. Results One hundred and forty-one patients were recruited in four clinical centers, and 125 patients completed the trial, of whom 66 were in the treatment group and 59 in the control group. An improvement was observed in both pain scores and sleep scores on week 1, 3 and 6 in both two groups, and the improvement was greater in gabapentin-treated group than that in the control group. The response rate was 29.58% and 57.75%, respectively in gabapentin-treated group on week 1 and 3, com-pared to 13.04% and 40.58%, respectively, in the control group (t = 5.94, 4.12, respectively, both P <0.05).Gabapentin was well tolerated, and the most common adverse events were dizziness, vertigo, somnolence and transient abnormality of hepatic function. Conclusion Gabapentin could markedly reduce pain intensity and improve sleep quality with a low incidence of adverse events in patients with postherpetic neuralgia.

  12. Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; Clausen, Rasmus P; Larsson, Orla M

    2009-01-01

    and BGT-1. When combined with the GAT1 selective inhibitor tiagabine, EF1502 was found to possess a synergistic anti-convulsant action in the Frings audiogenic seizure-susceptible mouse model of reflex epilepsy. This effect was subsequently attributed to inhibition of BGT-1. In this study, the anti-convulsant...... effect of the GAT2/3 inhibitor SNAP-5114 was assessed in the Frings audiogenic seizure-susceptible mouse alone, and in combination with tiagabine and EF1502. The results showed that SNAP-5114 produced a synergistic anti-convulsant effect in combination with EF1502 but not when used in combination...

  13. What Are the Treatments for Muscular Dystrophy?

    Science.gov (United States)

    ... effects. 5 Anticonvulsants. Typically taken for epilepsy, these drugs may help control seizures and some muscle spasms. Immunosuppressants. Commonly given to treat autoimmune diseases such as lupus and eczema, immunosuppressant drugs may ...

  14. Pharmacological Treatment Of Diabetic Peripheral Neuropathy

    OpenAIRE

    2015-01-01

    Pain modulation is a key treatment goal for diabetic peripheral neuropathy patients. Guidelines have recommended antidepressant, anticonvulsant, analgesic, and topical medications—both approved and off-label—to reduce pain in this population.

  15. Mood-stabilizing pharmacological treatment in bipolar disorders and risk of suicide

    DEFF Research Database (Denmark)

    Søndergård, Lars; Lopez, A.G.; Andersen, Per Kragh;

    2008-01-01

    Objectives: This study investigated the association between continued mood-stabilizing treatment (lithium and anticonvulsants) in bipolar disorder (BD) and the risk of suicide. Methods: Using linkage of national registers, the association between continued mood-stabilizing treatment and suicide....... Although the rate of suicide was higher during periods when patients purchased anticonvulsants (293 suicides per 100,000 person-years) than during periods with lithium (136 suicides per 100,000 person-years), the suicide rate decreased with the number of prescriptions in a rather similar way for patients...... first treated with lithium and patients first treated with anticonvulsants: patients who continued treatment with mood-stabilizing drugs had a decreased rate of suicide compared to patients who purchased mood stabilizers once only [rate ratio for anticonvulsants = 0.28, 95% confidence interval (CI) = 0...

  16. PRENATAL EXPOSURE TO PHENYTOIN, FACIAL DEVELOPMENT, AND A POSSIBLE ROLE FOR VITAMIN-K

    NARCIS (Netherlands)

    HOWE, AM; LIPSON, AH; SHEFFIELD, LJ; HAAN, EA; HALLIDAY, JL; JENSON, F; DAVID, DJ; WEBSTER, WS

    1995-01-01

    Ten patients with maxillonasal hypoplasia (Binder ''syndrome''), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate ca

  17. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    Directory of Open Access Journals (Sweden)

    Chanin Clark Wright

    2013-12-01

    Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

  18. One man's side effect is another man's therapeutic opportunity

    DEFF Research Database (Denmark)

    Jepps, Thomas Andrew; Olesen, S P; Greenwood, I A

    2013-01-01

    Retigabine is a first in class anticonvulsant that has recently undergone clinical trials to test its efficacy in epileptic patients. Retigabine's novel mechanism of action - activating Kv7 channels - suppresses neuronal activity to prevent seizure generation by hyperpolarizing the membrane...

  19. Optimization of Quantitative Proteomics Using 2-Dimensional Difference Gel Electrophoresis to Characterize Molecular Mechanisms of Chemical Warfare Nerve Agent Exposure in the Rat Brain

    Science.gov (United States)

    2010-11-01

    damaging effects of nerve agents. Currently, one prophylactic (pyridostigmine) and three therapeutic drugs (atropine, pralidoxime chloride, and diazepam ...and J.H. McDonough, Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication. Archives of

  20. Treatment of the Hyperactive Child

    Science.gov (United States)

    Wunderlich, Ray C.

    1973-01-01

    Described individually are the following forms of medical treatment for the hyperactive child: stimulants, tranquilizers, megavitamins, corticosteroids, antihistamines, anticonvulsants, food elimination, air filtration, allergic desensitization, perceptual motor training, and behavioral counseling. (DB)

  1. Drug: D00218 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ion map07017 Sulfonamide derivatives - diuretics map07033 Anticonvulsants map07054 Antiglaucoma agents map07...D00218 Acetazolamide (JP16/USP/INN) Ophthalmic Agents Ophthalmic Antiglaucoma Agents Acetazolamide D00218 Ac

  2. Drug: D01196 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available diuretics map07033 Anticonvulsants map07054 Antiglaucoma agents map07055 Sulfonamide derivatives - overview...ic Agents Ophthalmic Antiglaucoma Agents Acetazolamide D01196 Acetazolamide sodium (JAN) Target-based classi

  3. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB

    1998-01-01

    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incap

  4. [Not Quite] The Ketogenic Diet in a Pill

    Directory of Open Access Journals (Sweden)

    Andrew J Kim

    2015-04-01

    Full Text Available Researchers at Okayama University, Japan showed lactate dehydrogenase (LDH inhibition suppresses neuronal excitation in vitro, reduces EEG discharges and seizures in rodent models, and may provide a novel mechanism for anticonvulsant medications in human patients.

  5. Drug: D00304 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available POLG [HSA:5428] map07033 Anticonvulsants map07036 Calcium channel blocking drugs map07048 Antimigraine...oate semisodium (INN) Valproate D00304 Divalproex sodium (USP); Valproate semisodium (INN) Antimigraine Agen

  6. Prevalence of Neuropathic Pain and the Need for Treatment

    Directory of Open Access Journals (Sweden)

    Pat Morley-Forster

    2006-01-01

    There is an unmet need for the treatment of neuropathic pain as evidenced by reports of pain despite the use of opioids and anticonvulsants, continuing psychological difficulties, lack of access to treatments and patients seeking access to complementary therapy.

  7. Drug: D00538 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (6323) Dopaminergic synapse Enzyme: CYP3A4 [HSA:1576] map07033 Anticonvulsants map07057 Antiparkinson...m 113 Antiepileptics 1139 Others D00538 Zonisamide (JAN/USAN/INN) 116 Antiparkinsonian agents 1169 Others D0

  8. Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and Older

    Science.gov (United States)

    ... your browser. Home Osteoporosis Women Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and ... and anticonvulsants history of anorexia nervosa. What Is Osteoporosis? Osteoporosis is a disease that makes bones fragile ...

  9. Drug: D00280 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00280.gif Anticonvulsant Therapeutic category: 1139 ATC code: N03AE01 Benzodiazepines GABAA-receptor (benz...Agents Clonazepam D00280 Clonazepam (JP16/USP/INN) Anxiolytics Benzodiazepines Clonazepam D00280 Clonazepam

  10. Lamotrigine: Evidence of its utility in the bipolar inconvenience

    OpenAIRE

    Alexánder Pinzón Amado

    2001-01-01

    Anticonvulsants, including valproate and carbamazepine, haveestablished efficacy in the treatment of bipolar disorder (BD).Lamotrigine, a second generation anticonvulsant, has beenreported to have antimanic, antidepressant and mood-stabilizingeffects. There have been published to date several case reports,case series, open trials and two randomized controlled trialswith lamotrigine as monotherapy or as add-on treatment inpatients with BD. Mechanisms of actions proposed to explainthe mood-stab...

  11. Interactions between modulators of the GABAA receptor: Stiripentol and benzodiazepines

    OpenAIRE

    Fisher, Janet L.

    2011-01-01

    Many patients with refractory epilepsy are treated with polytherapy, and nearly 15% of epilepsy patients receive two or more anti-convulsant agents. The anti-convulsant stiripentol is used as an add-on treatment for the childhood epilepsy syndrome known as severe myoclonic epilepsy in infancy (Dravet Syndrome). Stiripentol has multiple mechanisms of action, both enhancing GABAA receptors and reducing activity of metabolic enzymes that break down other drugs. Stiripentol is typically co-admini...

  12. The effects of stiripentol on GABAA receptors

    OpenAIRE

    Fisher, Janet L.

    2011-01-01

    The anti-convulsant Stiripentol (Diacomit™) has been shown to have a positive impact on control of seizures for many patients with Dravet Syndrome. As with most anti-epileptic drugs, stiripentol has multiple mechanisms of action. Its direct anti-convulsant activity is likely due to enhancement of inhibitory, GABAergic neurotransmission. Stiripentol was shown to increase the activity of both neuronal and recombinant GABAA receptors at clinically relevant concentrations. At recombinant receptor...

  13. Effect of Eclipta alba on acute seizure models: a GABAA-mediated effect

    Directory of Open Access Journals (Sweden)

    M F Shaikh

    2013-01-01

    Full Text Available In the present study, anticonvulsant activity of methanol extract of Eclipta alba (10-200 mg/kg was studied using pentylenetetrazole- and picrotoxin-induced seizure models. Mechanism of effect of methanol extract of Eclipta alba was further elucidated by studying its GABA A receptor modulatory activity and its effect on levels of GABA in mice brain. Methanol extract of Eclipta alba exhibited potent anticonvulsant activity but has saturation of its pharmacological activity at 50 mg/kg. At the concentration of 10 mg/ml, contractions induced in guinea pig ileum was blocked by picrotoxin, but it didn′t not show any increase in GABA levels in mice brain after treatment. Hence, it can be concluded that methanol extract of Eclipta alba possesses potent anticonvulsant activity because of its positive modulatory effect on GABA A receptors.

  14. Convulsion-related activities of Scutellaria flavones are related to the 5,7-dihydroxyl structures.

    Science.gov (United States)

    Yoon, Seo Young; dela Peña, Ike Campomayor; Shin, Chan Young; Son, Kun Ho; Lee, Yong Soo; Ryu, Jong Hoon; Cheong, Jae Hoon; Ko, Kwang Ho

    2011-06-01

    We screened the major bioactive flavones isolated from Scutellaria baicalensis (baicalin, baicalein and oroxylin A) for their convulsion related activities. In electrogenic response score system and the pentylenetetrazole seizure model, baicalein but not oroxylin A and baicalin exhibited anticonvulsant effects. In vitro studies also revealed that baicalein induced intracellular Cl(-) influx, whereas oroxylin A blocked muscimol- and baicalein-induced intracellular Cl(-) influx. The anticonvulsant effect of baicalein was inhibited by flumazenil, a benzodiazepine(BZD) receptor antagonist. Therefore, anticonvulsive effect of baicalein was mediated by the BZD binding site of GABA(A) receptor. The 5, 7-dihydroxyl group is present in the structure of the three flavones. It is postulated that this group played a key role in inducing convulsion-related activities.

  15. Studies on the role of 5-HT2A and 5-HT2C receptor antagonist and effects of co-administration of Fluoxetines in regulating generalized seizures in albino rats

    Directory of Open Access Journals (Sweden)

    Vasant R Chavan

    2010-07-01

    Full Text Available Introduction: Epilepsy is due to imbalance between inhibitory & excitatory neurotransmitter release at synaptic level in brain such as GABA, Serotonin, Glutamate and nor epinephrine. Recently there are few reports suggesting that, 5-HT1A receptor antagonist with co-administration of fluoxetine has shown anticonvulsant activity. The present study is undertaken to evaluate the action of 5-HT2A/2C mediated anticonvulsant action of Trazodone in MES (Maximum Electro Shock model in albino rats. Materials & Methods: Fifty albino rats of 200-250 gms of either sex were divided into five groups each of 10 rats(n=10, Group–I received distil water 0.5ml oral, Group –II- received sodium valproate - 200mg/kg bw intra peritoneal(i.p.acted as positive control, Group –III- received Trazodone 54mg/bw, orally Group- IV- received sub-anticonvulsant dose of Fluoxetine 6mg/kg/bw i.p. Group- V- received Trazodone 54mg/kg/bw and Fluoxetine 6mg/kg bw. Subsequently all groups were subjected for MES. The results were analyzed by calculating the mean duration of convulsions & absence of HLE and comparison was done by student‘t’ test. Results: The present study revealed that sodium valproate showed 100% protection against MES as compared to negative control,(P<0.05. Trazodone showed 40% protection against MES& decrease in the duration of convulsions by 60%, and Fluoxitine sub-anticonvulsive dose combined with Trazodone 54 mg /kg b.w. has shown 90% protection against MES. The results are parallel to standard drug sodium valproate. Conclusion: Trazodone has exerted anticonvulsant activity, by enhancing 5-HT&NE extra cellular level in brain, and probably potentiated the action of sub anticonvulsive dose of fluoxetine in combination. However, further investigative studies are needed to confirm the potention of trazodone action.

  16. Ketogenic diet and astrocyte/neuron metabolic interactions

    Directory of Open Access Journals (Sweden)

    Vamecq Joseph

    2007-05-01

    Full Text Available The ketogenic diet is an anticonvulsant diet enriched in fat. It provides the body with a minimal protein requirement and a restricted carbohydrate supply, the vast majority of calories (more than 80-90% being given by fat. Though anticonvulsant activity of ketogenic diet has been well documented by a large number of experimental and clinical studies, underlying mechanisms still remain partially unclear. Astrocyte-neuron interactions, among which metabolic shuttles, may influence synaptic activity and hence anticonvulsant protection. The astrocyte-neuron metabolic shuttles may be themselves influenced by the availability in energetic substrates such as hydrates of carbon and fats. Historically, ketogenic diet had been designed to mimic changes such as ketosis occurring upon starvation, a physiological state already known to exhibit anticonvulsant protection and sometimes referred to as “water diet”. For this reason, a special attention should be paid to metabolic features shared in common by ketogenic diet and starvation and especially those features that might result in anticonvulsant protection. Compared to feeding by usual mixed diet, starvation and ketogenic diet are both characterised by increased fat, lowered glucose and aminoacid supplies to cells. The resulting impact of these changes in energetic substrates on astrocyte/neuron metabolic shuttles might have anticonvulsant and/or neuroprotective properties. This is the aim of this communication to review some important astrocyte/neuron metabolic interactions (astrocyte/neuron lactate shuttle, glutamateinduced astrocytic glycolysis activation, glutamate/glutamine cycle along with the neurovascular coupling and the extent to which the way of their alteration by starvation and/or ketogenic diet might result in seizure and/or brain protection.

  17. Functional roles of benzothiazole motif in antiepileptic drug research.

    Science.gov (United States)

    Amir, Mohammad; Hassan, Mohd Zaheen

    2013-12-01

    Benzothiazoles are promising candidates for the design of novel antiepileptic drugs. The endocyclic sulphur and nitrogen functions present in this heterocyclic nucleus have been shown to be critical for the anticonvulsant activity. The present review outlines the rational design and anticonvulsant potential of promising benzothiazole lead molecules. Particular focus has been placed on the structure activity relationship of different benzothiazole derivatives giving selected examples of molecules with significant activity being that these molecules may serve as prototypes for the development of more active antiepileptic drugs.

  18. Mechanism of the inhibitory effect of endogenous histamine on epilepsy in rats

    Institute of Scientific and Technical Information of China (English)

    ChenZhong

    2004-01-01

    Clinical data demonstrated that long-term epilepsy, especially among children, or ingesting anticonvulsant drugs over time are likely to result in cognitive deficits (e. g. memory or attention problems as well as other CNS side effects such as psychomotor speed abnormalities, somnolence, asthenia, and dizziness. New drug therapy has been expected. The histaminergic neuron system seems to be involved in various physiological and behavioral functions including sleep - wake cycles, stress behavior, neuroendocrine, learning and memory through histamine HI, H2 and H3 receptors. The role of brain histamine in regulating seizure susceptibility has been studied, and a possible anticonvulsant action of endogenous histamine has been postulated

  19. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund;

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were...

  20. Synergistic interaction of levetiracetam with gabapentin in the mouse 6 Hz psychomotor seizure model – a type II isobolographic analysis

    OpenAIRE

    Wlaz Aleksandra; Kondrat-Wrobel Maria W.; Zaluska Katarzyna; Kochman Ewelina; Rekas Anna R.; Luszczki Jarogniew J.

    2015-01-01

    This study was aimed at characterizing the anticonvulsant effects of levetiracetam in combination with gabapentin, in the mouse 6 Hz psychomotor seizure model. Herein, psychomotor seizures were evoked in male albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Type II isobolographic analysis was used to characterize the anticonvulsant interactions between the drugs in combination, for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. The type II isobolog...

  1. Drug: D02716 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02716 Drug Pregabalin (JAN/USAN/INN); Lyrica (TN) C8H17NO2 159.1259 159.2261 D0271...6.gif Anticonvulsant Therapeutic category: 1190 ATC code: N03AX16 GABA [CPD:C00334] analog Pregabalin binds ...C) classification [BR:br08303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AX Other antiepileptics N03AX16 Pregabalin... D02716 Pregabalin (JAN/USAN/INN) USP drug classification [BR:br08302] Anticonvulsan...ts Calcium Channel Modifying Agents Pregabalin D02716 Pregabalin (JAN/USAN/INN) C

  2. Valproate-induced hyperammonemic encephalopathy: a case report and brief review of the literature.

    Science.gov (United States)

    Sunkavalli, K Kiran; Iqbal, Fahad M; Singh, Balwinder; Koneru, Jayanth

    2013-01-01

    Almost 50 years after its discovery, valproic acid remains a mainstay in the treatment of epilepsy, both alone and in combination with other anticonvulsants. It is also associated with a hyperammonemic encephalopathy, when used in combination with other drugs. We present a case of valproate-induced hyperammonemic encephalopathy in a patient on multiple anticonvulsant and psychotropic medications. The patient presented with altered mental status and became progressively more obtunded and finally began to experience seizures. Her symptoms resolved with the discontinuation of valproic acid and with supportive care.

  3. Oxcarbazepine-induced drug rash with eosinophilia and systemic symptoms syndrome presenting as exfoliative dermatitis

    Directory of Open Access Journals (Sweden)

    Mahimanjan Saha

    2016-01-01

    Full Text Available Drug rash with eosinophilia and systemic symptoms (DRESS syndrome is a type of severe adverse cutaneous drug reaction characterized by fever, skin eruption, hematological abnormalities, and internal organ involvement. Although anticonvulsant drugs are mainly implicated in DRESS, newer anticonvulsants such as oxcarbazepine-induced definite cases of DRESS syndrome are rare and oxcarbazepine-induced DRESS syndrome presenting as exfoliative dermatitis is even rarer. We report a case of a 35-year-old male who developed DRESS syndrome presenting as exfoliative dermatitis after taking oxcarbazepine for 3 weeks.

  4. Oxcarbazepine-induced drug rash with eosinophilia and systemic symptoms syndrome presenting as exfoliative dermatitis.

    Science.gov (United States)

    Saha, Mahimanjan; Gorai, Surajit; Madhab, Vaswatee

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a type of severe adverse cutaneous drug reaction characterized by fever, skin eruption, hematological abnormalities, and internal organ involvement. Although anticonvulsant drugs are mainly implicated in DRESS, newer anticonvulsants such as oxcarbazepine-induced definite cases of DRESS syndrome are rare and oxcarbazepine-induced DRESS syndrome presenting as exfoliative dermatitis is even rarer. We report a case of a 35-year-old male who developed DRESS syndrome presenting as exfoliative dermatitis after taking oxcarbazepine for 3 weeks.

  5. Increase of the seizure threshold in C57BL/6 mice after citicoline administration.

    Science.gov (United States)

    Karpova, M N; Zin'kovskii, K A; Kuznetsova, L V; Klishina, N V

    2015-01-01

    We studied the dose-dependent effect of preventive intraperitoneal injection of citicoline (cytidine 5'-diphosphocholine) on acute generalized epileptiform activity in C57Bl/6 mice. The duration of citicoline action was also evaluated. Administration of citicoline in doses of 500 and 1000 mg/kg 1 h before treatment with the convulsant agent pentylenetetrazole produced an anticonvulsant effect. This effect was manifested in an increase of the threshold of clonic seizures and tonic phase of seizures with lethal outcome. Moreover, the latency of seizure development was elevated under these conditions. The anticonvulsant effect of citicoline persisted for 6 h after its injection.

  6. The metabolic effects of olanzapine and topiramate in rats and humans

    NARCIS (Netherlands)

    Evers, S.S.; van Dijk, G.; van Vliet, A.; Scheurink, A.J.W.

    2011-01-01

    In humans the anti-psychotic Olanzapine (OLZ) has negative side effects on metabolism: it causes weight gain and increases the risk of developing type 2 Diabetes. The anti-convulsant Topiramate (TPM) has the opposite effects: it reduces body weight and improves insulin sensitivity. Because of this,

  7. Epidemiology of Osteoporosis in Women with Cognitive Impairment

    Science.gov (United States)

    Schrager, Sarina

    2006-01-01

    Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…

  8. Drug: D05714 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available oprotective] N-methyl-D-aspartate receptor antagonist [HSA:2902 2903 2904 2905 2906...D05714 Drug Remacemide hydrochloride (USAN) C17H20N2O. HCl 304.1342 304.8144 D05714.gif Anticonvulsant [neur

  9. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K;

    2001-01-01

    of 512 microM and 6 microM, respectively) at concentrations lower than those used for brain slice recordings. Riluzole, a potent neuroprotective drug with anti-ischemic, anticonvulsant and sedative effects currently used in the treatment of amyotrophic lateral sclerosis, activates SK3 channels...

  10. Pyrimidine as antiinflammatory agent: A review

    Directory of Open Access Journals (Sweden)

    Amir M

    2007-01-01

    Full Text Available Pyrimidine nucleus exhibited remarkable pharmacological activities. Literature indicates that compounds having pyrimidine nucleus have wide range of therapeutic uses that include antiinflammatory, antibacterial, anticancer, antiviral, antiHIV, antimalarial, antihypertensive, sedatives and hypnotics, anticonvulsant and antihistaminic. The present review provides a broad view of the antiinflammatory activity possessed by compounds having a pyrimidine nucleus.

  11. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.

    1991-01-01

    Current progress on this research includes the synthesis of chemical structures for malignant brain tumors. These structures include boron-containing derivatives of lipophilic anticonvulsants and CNS depressants; carboranyl precursors of nucleic acids and related structures; and carboranyl amino acids. Cellular uptake and persistence studies have also been carried out with F98 rat glioma cells. 1 fig., 1 tab.

  12. Carbamazepine-Induced Hyponatremia in Patients with Mental Retardation.

    Science.gov (United States)

    Kastner, Ted; And Others

    1992-01-01

    This study of 40 patients with mental retardation receiving carbamazepine found hyponatremia in only 5 percent of these patients and found a statistically, but not clinically, significant decrease in serum sodium levels in patients receiving anticonvulsant polytherapy. Results support the use of this drug with patients with mental retardation and…

  13. Transient inhibitory seizures mimicking crescendo TIAs.

    Science.gov (United States)

    Lee, H; Lerner, A

    1990-01-01

    Somatic inhibitory seizures are thought to occur rarely. We describe a patient with somatic inhibitory seizures who initially presented with a clinical picture of crescendo transient ischemic attacks. He did not improve with anticoagulation, but the episodes ceased promptly after the administration of an anticonvulsant.

  14. Carbamazepine-induced upregulation of adenosine A(1)-receptors in astrocyte cultures affects coupling to the phosphoinositol signaling pathway

    NARCIS (Netherlands)

    Biber, K; Fiebich, BL; Gebicke-Harter, P; van Calker, D

    1999-01-01

    The anticonvulsant and antibipolar drug carbamazepine (CBZ) is known to act as a specific antagonist at adenosine A(1)-receptors. After a 3-week application of CBZ, A(1)-receptors are upregulated in the rat brain. We have investigated the consequences of this upregulation for the A(1)-receptor-media

  15. Landau-Kleffner syndrome: study of four cases

    Directory of Open Access Journals (Sweden)

    Santos Lúcia H. Coutinho dos

    2002-01-01

    Full Text Available We describe four patients with clinical features of Landau-Kleffner syndrome and discuss electroencephalographic features, treatment and prognosis. Anticonvulsants and prednisone were used for treatment with good control of seizures in all cases and a less effect response in acquired aphasia. Further studies are necessary to elucidate the causes and management of this syndrome.

  16. Epilepsy with myoclonic absences - favourable response to add-on rufinamide treatment in 3 cases

    DEFF Research Database (Denmark)

    Häusler, M; Kluger, G; Nikanorova, M

    2011-01-01

    Epilepsy with myoclonic absences (EMA) is a rare epileptic syndrome with frequently poor response to antiepileptic treatment. Rufinamide (RUF) is a relatively new EMEA- and FDA-approved anticonvulsant licensed as an orphan drug for the adjunctive treatment of patients with Lennox-Gastaut syndrome....

  17. Removal of 10-hydroxycarbazepine by plasmapheresis

    DEFF Research Database (Denmark)

    Christensen, J; Balslev, T; Villadsen, J;

    2001-01-01

    with studies on other anticonvulsant medications (carbamazepine, valproic acid, phenobarbital, and phenytoin), indicating that minor fractions (2% to 10%) of body stores of these drugs are depleted during plasmapheresis. The authors conclude that it is unnecessary to adjust the oxcarbazepine dosage when...

  18. Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice

    Institute of Scientific and Technical Information of China (English)

    Abrar M Tamboli; Rukhsana A Rub; Pinaki Ghosh; SL Bodhankar

    2012-01-01

    Objective:To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models. Methods:The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison. Results:Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P<0.050–0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model. Conclusions:In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.

  19. Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2011-01-01

    Full Text Available Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN, and Stevens-Johnson syndrome (SJS. We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

  20. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    Qiao, X.

    2013-01-01

    Certain antiepileptic drugs (e.g. carbamazepine and lamotrigine) block sodium channels in an use-dependent manner and this mechanism contributes to the anti-convulsant properties of these drugs. There are, however, subtle differences in sodium current blocking properties of the antiepileptic drugs w