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Sample records for anticonvulsants

  1. Acne and anticonvulsants.

    OpenAIRE

    Greenwood, R; Fenwick, P B; Cunliffe, W J

    1983-01-01

    The severity of acne and rate of excretion of sebum were assessed in 243 patients with epilepsy taking various anticonvulsants who were in hospital long term and in matched controls derived from a normal population of 2176 people. Neither the prevalence of acne nor the sebum excretion rate significantly increased in the patients compared with the controls or in patients taking phenytoin compared with those not. It is concluded that anticonvulsant treatment does not cause acne.

  2. Clinical pharmacokinetics of anticonvulsants.

    Science.gov (United States)

    Hvidberg, E F; Dam, M

    1976-01-01

    Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies. The most important advantage is that the frequent interindividual variation in the plasma level/dose ratio for these drugs can be circumvented by plasma level monitoring. For several anticonvulsants the brain concentration is shown to parallel the plasma concentration. Phenytoin (diphenylhydantoin) is stil the most important anticonvulsant and the one for which kinetics have been thoroughly investigated in man. These investigations have revealed several reasons for the wellknown difficulties in using this drug clinically. The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose. The elimination capacity is saturable causing dose dependent kinetics, which again means disproportional changes in plasma level with changes in dose. Great individual variations exist in the rate of metabolism, and several pharmacokinetic drug interactions are known. As an optimum therapeutic plasma concentration range has been established monitoring plasma levels must be strongly advocated. Interpretation of plasma levels in uraemic patients must take into account decreased protein binding of the drug. Carbamazepine is probably as effective as phenytoin. The elimination is a first order process, but the rate of metabolism increases after a few weeks' treatment. An active metabolite (epoxide) may be the cause of some side-effects. Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary. An optimum therapeutic concentration range has been suggested and plasma monitoring is advocated, along with that of the active metabolite, the epoxide. Phenobarbitone is still much used but its kinetics have been investigated to a lesser extent. The main problem is the variability in the rate of elimination. In children the half

  3. [Anticonvulsant agents in neuralgic pain.].

    Science.gov (United States)

    Jurna, I; Zenz, M

    1992-06-01

    The anticonvulsants, carbamazepine, clonazepam, phenytoin, and valproic acid are capable of depressing attacks of shooting pain in neuralgia. Shooting pain is perceived in trigeminal, intercostal, and other neuralgias, as a consequence of infectious diseases such as herpes zoster, and in the course of polyneuropathies of various causes. It is due to injury of nociceptive afferents, which generate bursts of activity in response to appropriate environmental changes. The anticonvulsant agents have no analgesic property per se, so that background pain remains unchanged. The depression of shooting pain results from the anticonvulsant action of the compounds. Both carbamazepine and phenytoin block synaptic transmission of neuronal hyperactivity by a direct depressant action that includes reduction of sodium conductance and by activation of inhibitory control. Clonazepam and valproic acid act by enhancing GABA-mediated inhibition of synaptic transmission. Carbamazepine is by far the most widely used compound; phenytoin, clonazepam, and valproic acid are not so popular because of their side effects. PMID:18415623

  4. 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 ...

  5. Impaired biotin status in anticonvulsant therapy

    OpenAIRE

    Krause, Klaus-Henning; Berlit, Peter; Bonjour, Jean-Pierre

    1982-01-01

    In 264 epileptics undergoing long-term therapy with anticonvulsants, significantly reduced plasma biotin levels were found compared with a normal control group: 74% of the epileptics had biotin levels for those treated with sodium valproate were higher than for those treated with phenytion, primidone, or carbamazepine. The observed reduction in biotin levels might be a factor influencing the efficacy of these three antionvulsants.

  6. 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.

  7. On the anticonvulsant activity of kaurenic acid.

    Science.gov (United States)

    Daló, Nelson L; Sosa-Sequera, Miriam C; Usubillaga, Alfredo

    2007-09-01

    Kaurenic acid [(-)-kaur-16-en-19-oic acid] is a diterpene isolated from the aerial parts of Espeletia semiglobulata, one of 85 species of Espeletiinae found in Venezuela. Its anticonvulsive activity was studied using two different models of experimental seizures: spinal seizures induced by sudden cooling (SSSC) in amphibians and seizures induced by pentylenetetrazol (PTZ) in mice. In SSSC, kaurenic acid (KA) inhibited the tonic hind-limb extension with an ED50 of 2.5 mg/kg. It was 4-fold more potent than known anticonvulsant drugs such as carbamazepine and phenytoin and 100-fold more potent than valproic acid. However, KA as well as valproic acid were ineffective against the clonic phase of SSSC. In the PTZ-induced seizures, KA at doses of 0.625 and 1.25 mg/kg increased the latency of seizure onset and protected against generalized clonic-tonic seizures by 45% and 65%, respectively. The sedative effects of KA had an ED50 of 8.5 mg/kg in mice and 75 mg/kg in amphibians. This work provides experimental evidence supporting the potential value of kaurenic acid as an anticonvulsive drug. PMID:17853794

  8. 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.

  9. [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) PMID:7840410

  10. 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.

  11. ANTICONVULSANT ACTIVITY OF MORINGA OLEIFERA LEAF

    OpenAIRE

    Amrutia Jay N; Lala Minaxi; Srinivasa U; Shabaraya A.R.; Moses Rajan Semuel

    2011-01-01

    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 ref...

  12. Adverse reactions to new anticonvulsant drugs.

    Science.gov (United States)

    Wong, I C; Lhatoo, S D

    2000-07-01

    A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to

  13. 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

  14. Anti-convulsant therapy in eclampsia.

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    Maheshwari J

    1989-04-01

    Full Text Available Seventy four patients presented with eclampsia at N.W.M. Hospital. Bombay. Among the patients with eclampsia, 64.9% were primis, 29.7% were gravida II-IV and 5.4% were grand multis. As many as 40.5% patients were less than 20 years of age, while 2.7% were over 30 years of age. 48.7% had antepartum convulsions, 40.5% had intrapartum convulsions, while 8 patients convulsed in the postpartum period. Besides standard management of eclamptic patients, 3 protocols of anticonvulsant therapy were utilised. 27% were managed with diphenyl hydantoin sodium, 43% with magnesium sulphate, and 30% by combination of diazepam and pentazocine. The maternal and perinatal outcome was evaluated. Control of convulsions was superior with magnesium sulphate while perinatal outcome was best with diphenyl hydantoin.

  15. Benzothiazole incorporated barbituric acid derivatives: synthesis and anticonvulsant screening.

    Science.gov (United States)

    Siddiqui, Nadeem; Ahsan, Waquar

    2009-08-01

    A series of 1-(6-substituted-1,3-benzothiazol-2-yl)-3-(substituted phenyl)hexahydro-2,4,6-pyrimidinetriones 4a-t were synthesized starting from substituted anilines. These compounds contained two active anticonvulsant pharmacophores, benzothiazole and barbituric acid. Structures of the compounds were confirmed on the basis of different spectroscopic techniques. All the compounds were evaluated for their anticonvulsant activity. Three compounds 4c, 4d, and 4s showed promising anticonvulsant activities in Maximal Electroshock Seizure test (MES) and subcutaneous pentylenetetrazole test (scPTZ). They also displayed a wide safety profile when tested for the minimal motor impairment test. PMID:19565603

  16. 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.

  17. 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...

  18. Bone mineral density, vitamin D and anticonvulsant therapy

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    FILARDI SILVANA

    2000-01-01

    Full Text Available The aim of this study was to assess bone mineral density and vitamin D metabolism in patients on chronic anticonvulsant therapy. METHODS: Sixty-nine men, outpatients on chronic anticonvulsant therapy, who had been treated for at least 5 years, were studied, comparing them to thirty healthy controls. Bone mineral density was measured as well as serum levels of calcium, ionized calcium, alkaline phosphatase, PTH, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. RESULTS: No differences in bone mineral density, serum levels of vitamin D and intact-PTH were observed between patients and controls. Bone mineral density was not associated with chronic anticonvulsant therapy. CONCLUSION: Those adult patients who were on chronic anticonvulsant therapy and who lived in low latitude regions had normal bone mineral density as well as vitamin D serum levels.

  19. ANTICONVULSANT ACTIVITY OF MORINGA OLEIFERA IN SWISS ALBINO MICE

    OpenAIRE

    Anu Elizabeth Joy; Padmini Thalanjeri; Shyamjith Manikkoth

    2015-01-01

    Objectives : The aim of the study was to investigate anticonvulsant effect of Moringa oleifera on maximal electroshock (MES), pentylenetetrazole (PTZ) and pilocarpine induced seizures. Methods : The ethanolic extract of Moringa oleifera leaves (200mg/ Kg) was used to study its anticonvulsant effect on MES, PTZ and pilocarpine induced seizures in Swiss albino mice. Suppression of the tonic hind limb extension, duration of convulsion, abolition of convulsions was noted respectively for the abov...

  20. 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.

  1. Anticonvulsant and behavioral effects of muscimol in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Tichá, Kateřina; Mikulecká, Anna

    2014-01-01

    Roč. 1582, SEP 25 (2014), s. 227-236. ISSN 0006-8993 R&D Projects: GA ČR(CZ) GAP304/10/1274 Grant ostatní: Univerzita Karlova(CZ) 92310 Institutional support: RVO:67985823 Keywords : anticonvulsant action * pentetrazol * cortical afterdischarges * motor performance * ontogeny * rat Subject RIV: FH - Neurology Impact factor: 2.843, year: 2014

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

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    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.

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

    OpenAIRE

    Mojtaba Keshavarz; Alireza Showraki; Masoumeh Emamghoreishi

    2013-01-01

    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 convuls...

  4. 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.

  5. Anticonvulsant hypersensitivity syndrome associated with carbamazepine administration: Case series

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    Maulin Mehta

    2014-01-01

    Full Text Available Hypersensitivity reactions are common adverse drug reactions (ADRs associated with antiepileptics. Carbamazepine is one of the routinely prescribed drugs for the treatment of epilepsy and neuropathic pain. ADRs due to carbamazepine range from mild maculopapular rash to severe anticonvulsant hypersensitivity syndrome (AHS. AHS is the triad of fever, rash, and internal organ involvement occurring 1-8 weeks after exposure to an anticonvulsant (1 in 1,000 to 10,000 exposures. Spontaneously reported three cases of AHS-drug hypersensitivity reactions induced by carbamazepine are discussed here. Seven to ten days after starting therapy, patients developed maculopapular skin rashes, fever and liver or kidney involvement. The causal relationship between drug and ADR was found to be ′certain′ in one case and ′probable′ in other two cases with both WHO-UMC and Naranjo causality assessment scale. All the three cases show category 4a according to Hartwig′s severity scale as ADR was the cause for hospital admission. On assessing preventability of ADRs by modified Schumock and Thorntons′ scale, one case was falling into category of ′definitely preventable′ and other two were ′not preventable′. AHS is rare but serious reaction with carbamazepine which requires vigilant monitoring by physicians to avoid major consequences.

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

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    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.

  7. Synthesis and Anticonvulsant Activity of Some Newer Semicarbazone Derivatives

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    Shahnawaz Sameem

    2012-07-01

    Full Text Available A series of 4-(3-Chlorophenyl-1-(substituted acetophenone semicarbazones 3(a-j was synthesized by starting with 3-chloroaniline which on reaction with sodium cyanate yielded 1-(3’-chlorophenyl urea (1 followed by reaction with hydrazine hydrate in the presence of ethanol gave 4-(3’-chlorophenyl semicarbazide (2. Compound (2 on condensation with substituted acetophenone gets converted in to final compounds 3(a-j. The purity of the newer compounds was checked by m.p. and TLC analysis. The structures of the newly synthesized compounds were characterized by FTIR, 1H NMR, EIMS-spectral data and elemental analysis. All the synthesized compounds were evaluated for their anticonvulsant activity by Maximal Electroshock (MES method by using phenytoin as standard at a concentration of 30 mg/kg. The anticonvulsant effect of the newly synthesized compounds was assessed by absence or reduction of hind limb tonic extensor phase. Among the synthesized derivatives compounds 3e and 3j were found to be the most potent compounds in the series.

  8. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    Science.gov (United States)

    Tolner, Else A.; Hochman, Daryl W.; Hassinen, Pekka; Otáhal, Jakub; Gaily, Eija; Haglund, Michael M.; Kubová, Hana; Schuchmann, Sebastian; Vanhatalo, Sampsa; Kaila, Kai

    2010-01-01

    Purpose CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and a non-human primate and based on these data, preliminary tests were carried out in humans. Methods In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. 5% CO2 was applied for 5 minutes, 3 minutes before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG and received 5% CO2 in medical carbogen shortly after electrographic seizure onset. Results In rats, 5% CO2 strongly suppressed cortical afterdischarges, by ca. 75%, while responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO2 from 37 to 44-45 mmHg (corresponding to inhalation of 5% CO2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by ca. 25%. In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO2 was started after seizure generalization. Conclusions 5% CO2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO2 can be used for acute treatment to suppress seizures in epilepsy patients. PMID:20887367

  9. Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy.

    Science.gov (United States)

    Armstrong, Terri S; Grant, Robin; Gilbert, Mark R; Lee, Jong Woo; Norden, Andrew D

    2016-06-01

    Seizures are a well-recognized symptom of primary brain tumors, and anticonvulsant use is common. This paper provides an overview of epilepsy and the use of anticonvulsants in glioma patients. Overall incidence and mechanisms of epileptogenesis are reviewed. Factors to consider with the use of antiepileptic drugs (AEDs) including incidence during the disease trajectory and prophylaxis along with considerations in the selection of anticonvulsant use (ie, potential side effects, drug interactions, adverse effects, and impact on survival) are also reviewed. Finally, areas for future research and exploring the pathophysiology and use of AEDs in this population are also discussed. PMID:26527735

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

    Science.gov (United States)

    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. PMID:20095393

  11. Efficiency of combined carbamazepine and nootropics to reduce side effect of anticonvulsant therapy

    OpenAIRE

    Ivanov A.V.; Opryshko V.I.

    2013-01-01

    Background. The high rate of epileptic disease spreading determines the need of antiepileptic drugs investigation. Carbamazepine, being one of the most effective anticonvulsant drugs, has a wide spectrum of common side effects, and one of the supposed ways to solve this problem is to combine carbamazepine with nootrops. The possibility of the combined anticonvulsant and nootropic therapy still needs further researches. Objective. To study the efficiency of the combined carbamazepine and nootr...

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

    OpenAIRE

    Girish Gowda; Kuntal Das; Vaibhav Bhosle; John Wilking Einstein; Benson Mathai K

    2012-01-01

    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 convulsio...

  13. Triazolines XIII: delta 2-1,2,3-triazolines, a new class of anticonvulsants.

    Science.gov (United States)

    Kadaba, P K

    1984-06-01

    A series of 1,5-diaryl-delta 2-1,2,3-triazolines has been synthesized and evaluated for the first time as potential anticonvulsant agents using the standard subcutaneous pentylenetetrazol seizure threshold and maximal electroshock seizure tests. Out of the 31 triazolines that were screened, 11 exhibited moderate anticonvulsant activity; 9 of the compounds afforded protection against pentylenetetrazol-induced seizures, while two antagonized electrically induced convulsions. PMID:6737279

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Magnesium sulphate as an anticonvulsant in the management of eclampsia

    International Nuclear Information System (INIS)

    Objective: To evaluate the use of magnesium sulphate (MgSO/sub 4/) as an anticonvulsant in the management of eclamptic patients. Patients and Methods: Out of a total of 6050 pregnant women, 31 patients had eclampsia and were managed according to the set protocol. MgSO/sub 4/ 'Nas given to eclamptic patients according to protocol who had no contraindication to this agent. Recurrence of convulsion, side effects of magnesium sulphate, maternal and fetal outcome was noted. Results: Over two years' study period, out of 6050 patients, 31 were admitted with eclampsia (0.51 %). There was no maternal death. Out of 31 eclamptic patients only 5 patients were booked. Twenty-two patients (70.9%) were primigravida and 9 (29%) were multigravida. Seventeen (54%) were less than 20 years of age, 22 (79.9%) patients were admitted with antepartum and 6 (19.35%) had postpartum eclampsia. Magnesium sulphate was effective in 29 (93.54%) patients. Fifteen patients delivered by caesarean (C) section and 16 delivered vaginally. Twenty-nine (93.5%) babies were born alive. Two patients had recurrent convulsion i.e. 6.4%. Only one patient had respiratory depression after the use of magnesium sulphate. Conclusion: Eclampsia was well controlled by the use of MgSO/sub 4/. There were only 2 patients who had recurrence of convulsion. Convulsions were controlled in 29 (93.54%) patients despite lack of monitoring facilities of serum magnesium level. (author)

  16. [Anticonvulsants and antipsychotics in the treatment of bipolar disorder].

    Science.gov (United States)

    Moreno, Ricardo Alberto; Moreno, Doris Hupfeld; Soares, Márcia Britto de Macedo; Ratzke, Roberto

    2004-10-01

    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 effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics. PMID:15597138

  17. Quantitative determination of bone mineral concentrations using quotient densitometry in patients under long-term anticonvulsant therapy

    International Nuclear Information System (INIS)

    The effect on bone mineral concentration of anticonvulsive long-term therapy was investigated in order to find out if there is a relation between the occurence and extent of osteomalacial lesions on the one hand and the type and time of application of anticonvulsants. The hydroxyl apatite content was determined by X-ray densitometry. The method is considered to be suitable for yearly skeletal monitoring of epilepticians treated with anticonvulsants. (orig./HP)

  18. Anticonvulsant activity of Citrus aurantium blossom essential oil (neroli): involvment of the GABAergic system.

    Science.gov (United States)

    Azanchi, Taravat; Shafaroodi, Hamed; Asgarpanah, Jinous

    2014-11-01

    Citrus aurantium L. blossoms are an important medicinal plant part in Iran and some other countries. It is used in traditional medicine as an antiseizure and anticonvulsant natural agent. Early in vitro research of the anticonvulsant activity of the blossom extracts were done but there has been no investigation focused on the blossom essential oil and its anticonvulsant activity. The anticonvulsant activity of the essential oil of C. aurantium blossoms (neroli) was investigated. The anticonvulsant activity of neroli was assessed in pentylenetetrazole (PTZ)-induced convulsion by i.v. and i.p. methods and maximal electroshock (MES) in mice, with diazepam as the standard drug. While mechanistic studies were conducted using flumazenil, a GABA A-benzodiazepine receptor complex site antagonist. Neroli produced protection against clonic by i.v adminiatration of PTZ at 20 and 40 mg/kg, compared with protection with benzodiazepine. The mean onset and percentage protection against convulsion in neroli-treated mice were reduced by flumazenil. Intraperitonaeal PTZ also decreased the latency of clonic seizure in the neroli (40 mg/kg) treated group. We also showed that neroli (20 and 40 mg/kg), exhibited inhibition of the tonic convulsion induced by MES and decreased the mortality rate. Neroli was analyzed by GC and GC-MS and twenty three constituents, representing 91.0 % of the chromatographical oil were identified. The major components of neroli were characterized as linalool (28.5%), linalyl acetate (19.6%), nerolidol (9.1%) E,E-farnesol (9.1%), α-terpineol (4.9%) and limonene (4.6%) which might be responsible for the anticonvulsant activity. The results suggest that neroli possesses biologically active constituent(s) that have anticonvulsant activity which supports the ethnomedicinal claims of the use of the plant in the management of seizure. PMID:25532295

  19. 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

  20. New imidazo[1,2-a]pyridines carrying active pharmacophores: synthesis and anticonvulsant studies.

    Science.gov (United States)

    Ulloora, Shrikanth; Shabaraya, Ramakrishna; Aamir, Syed; Adhikari, Airody Vasudeva

    2013-03-01

    Five new series of imidazo[1,2-a]pyridines carrying biologically active pyrazoline (4a-e), cyanopyridone (5a, b), cyanopyridine (6a-f), 2-aminopyrimidine (7a-f) and pyrimidine-2-thione (8a-d) systems were designed and synthesized as prominent anticonvulsant agents. The target compounds were screened for their in vivo anticonvulsant activity following maximal electroshock (MES) and subcutaneous pentylene tetrazole (scPTZ) methods at a small test dose of 10 mg/kg. Further, Rotarod toxicity method was used to study the toxicity profile of selected compounds. Compounds 4b, 5a, 5b, 6a, 7e and 8d possessing 4-fluorophenyl substituent at 2nd position of imidazo[1,2-a]pyridine ring displayed potent anticonvulsant activity without displaying any toxicity. Enhanced activity profile was observed for new compounds in PTZ method over MES method. PMID:23352511

  1. Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.

    Science.gov (United States)

    Oliveira, Cleide Correia de; Oliveira, Clarissa Vasconcelos de; Grigoletto, Jéssica; Ribeiro, Leandro Rodrigo; Funck, Vinícius Rafael; Grauncke, Ana Cláudia Beck; Souza, Thaíze Lopes de; Souto, Naieli Schiefelbein; Furian, Ana Flávia; Menezes, Irwin Rose Alencar; Oliveira, Mauro Schneider

    2016-03-01

    Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of β-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of β-caryophyllene (0, 10, 30, or 100mg/kg). After 60min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60mg/kg). We found that β-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of β-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of β-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs. PMID:26827298

  2. Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H-one Derivatives

    Directory of Open Access Journals (Sweden)

    Safinaz Abbas

    2008-10-01

    Full Text Available A number of 3-substituted-2-(substituted-phenoxymethyl quinazolin-4(3H-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS. A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity.

  3. Triazolines 26: 1-Aryl-5-amido-1,2,3-triazolines, a new group of triazoline anticonvulsants. Effect of 5-substitution on anticonvulsant activity.

    Science.gov (United States)

    Kadaba, P K

    1996-01-01

    Studies in our laboratories have led to the discovery of the delta 2-1,2,3-triazolines as a unique family of anticonvulsant agents hitherto unknown. The anticonvulsant activity of 1,5-diaryl- and 1-aryl-5-pyridyltriazolines was previously reported; this paper describes the evaluation of two series of 1-aryl-5-amido-1,2,3-triazolines, A and B, where the 5-amido groups are (2-oxo-1-pyrrolidino)- (1-8) and (N-methyl-N-acetamido)- (9-15), respectively. The 1-aryl-5-(2-oxo-1-pyrrolidino)-1,2,3-triazolines of the A series, which are uniquely substituted with the pyrrolidinone lactam ring, a cyclic gamma-aminobutyric acid (GABA) structure, seem to function by enhancing inhibitory GABAergic mechanisms. Radioligand binding studies for the two most active triazolines 2 and 7, indicate that both compounds strongly inhibit the specific binding of [3H]GABA to GABAB receptor sites, with Ki = 1.7 and 0.91 microM respectively. The anticonvulsant activity among the various groups of triazolines studied so far appears to be dependent on the 5-substituent groups: 4-pyridyl- > 2-oxo-1-pyrrolidino- > N-methyl-N-acetamido- > 3-pyridyl > or = aryl approximately 2-pyridyl > 2-quinolyl. PMID:8881374

  4. Age and activation determines the anticonvulsant effect of ifenprodil in rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2014-01-01

    Roč. 387, č. 8 (2014), s. 753-761. ISSN 0028-1298 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : NMDA receptors * NR2B subunit * anticonvulsant action * ontogeny * rat Subject RIV: FH - Neurology Impact factor: 2.471, year: 2014

  5. Anticonvulsant Effects of Lippia citriodora (Verbenaceae) Leaves Ethanolic Extract in Mice: Role of GABAergic System

    Science.gov (United States)

    Rashidian, Amir; Farhang, Forogh; Vahedi, Habib; Dehpour, Ahmad Reza; Ejtemai Mehr, Shahram; Mehrzadi, Saeed; Rezayat, Seyed Mahdi

    2016-01-01

    Background: Lippia citriodora Kunth is one of the Iranian traditional medicines for the treatment of convulsive disorders. The goal of this study is to investigate the anticonvulsant activity of the plant's leave ethanolic extract against electro- and chemoconvulsant-induced seizures in mice. Methods: The anticonvulsant activity of the extract (200, 400, 800 mg/kg, per os, p.o.) was investigated in pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice. Diazepam (1 mg/kg) and phenytoin (25 mg/kg) intraperitoneally (i.p.) were used as reference drugs. In addition, for investigating the role of GABAergic system, flumazenil (2 mg/kg, i.p.) was also injected before L. citriodora. Results: The extract had not any toxicity and significantly decreased the duration and increased the latency of the seizures induced by PTZ (90 mg/kg). In the MES test, L. citriodora displayed statistically significant reduction in hind limb tonic extension duration in a nondose-dependent manner. Flumazenil reversed the anticonvulsant activity of the plant's extract in the PTZ model. Conclusions: The results propose that L. citriodora leave ethanolic extract has anticonvulsant activity against convulsive disorders. It seems that this plant's extract generates its antiseizure effect through GABAergic system potentiation. Further studies will be needed in order to investigate the exact mechanisms of it. Moreover, one may conclude that the present results are in accordance with the positive effect of L. citriodora extract to treat convulsion mentioned in old Iranian literature.

  6. 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 ext...

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

    International Nuclear Information System (INIS)

    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.)

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

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    ). Hippocampal slice cultures were submitted to 1 h OGD and the resulting cell death was quantified 24 h later using a novel automated fluorescent scanning method. The classical anticonvulsants phenobarbital, phenytoin, ethosuximide, chlordiazepoxide and midazolam all significantly and dose-dependently reduced...

  9. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

    Science.gov (United States)

    Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

    2014-05-01

    Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (Pthalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. PMID:24735834

  10. Comparing the Anticonvulsant Effects of Low Frequency Stimulation of Different Brain Sites on the Amygdala Kindling Acquisition in Rats

    OpenAIRE

    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-freq...

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

    OpenAIRE

    Vaibhav Bhosle

    2013-01-01

    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 si...

  12. 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.

  13. 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. PMID:26258457

  14. 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...... among all persons who were registered in Denmark on January 1, 1995, all patients with a diagnosis of a single manic episode or bipolar disorder between January 1, 1994, and December 31, 2012 (n =10 591), and all patients exposed to either lithium (n = 26 731) or anticonvulsants (n=420 959). Cohort 2...

  15. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

    Science.gov (United States)

    McCarren, Hilary S; McDonough, John H

    2016-06-01

    Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID:27258770

  16. 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

  17. The Anticonvulsant and Antioxidant Effects of Berberine in Kainate-induced Temporal Lobe Epilepsy in Rats

    OpenAIRE

    Mojarad, Tourandokht Baluchnejad; Roghani, Mehrdad

    2014-01-01

    Introduction Temporal lobe epilepsy (TLE) is a long lasting neurological disorder in which patients suffer from spontaneous seizures. New treatments with novel mechanisms of action are needed to help those patients whose seizures are resistant to available drugs. In this study, we investigated the possible neuroprotective effect of berberine in an intrahippocampal kainate model of TLE in rat. Methods In the present study, the anticonvulsant and antioxidant effects of intraperitoneal administr...

  18. 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. PMID:26702549

  19. Anticonvulsant treatments of dysphoric mania: a trial of gabapentin, lamotrigine and carbamazepine in Iran

    OpenAIRE

    Mokhber, Naghmeh; Lane, Carol J.; Azarpazhooh, Mohamad R; Elham SALARI*; Fayazi, Reza; Shakeri, Mohamad T; Young, Allan H.

    2008-01-01

    The treatment of dysphoric mania is challenging given the need to treat symptoms of both depression and mania simultaneously without provoking any clinical exacerbation. The newer antiepileptic drugs such as gabapentin, lamotrogine, and carbamazepine are often used as adjuncts to either lithium or valproic acid in the treatment of bipolar disorder. We decided to undertake a monotherapy trial because previous evidence suggested mixed states may be more responsive to anticonvulsants than more t...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis

    OpenAIRE

    Marylou V. Solbrig; Adrian, Russell; Wechsler, Steven L.; Koob, George F.

    2006-01-01

    Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s...

  2. Evaluation of the Sedative and Anticonvulsant Properties of Three Cameroonian Plants

    OpenAIRE

    Okomolo, Fleur Clarisse Moto; Mbafor, Joseph Tanyi; Bum, Elisabeth Ngo; Kouemou, Nadège; Kandeda, Antoine Kavaye; Talla, Emmanuel; Dimo, Théophile; Rakotonirira, Alice; Rakotonirira, Silvère Vincent

    2011-01-01

    Millettia thonningii, Ocinum sanctum and Securitaca longepedunculaca are used in traditional medicine in Cameroon to treat epilepsy, insomnia and headaches. Animal models of epilepsy (maximal electroshock (MES), n-methyl-d-aspartate (NMDA), pentylenetetrazol (PTZ), isonicotinic hydrazide acid (INH), picrotoxine (PIC) and strychnine (STR)-induced convulsions or turning behavior were used to evaluate anticonvulsant activity while diazepam-induced sleep test was used to evaluate sedative activit...

  3. Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity.

    OpenAIRE

    Herrick, A. L.; McColl, K E; Moore, M R; Brodie, M J; Adamson, A R; Goldberg, A

    1989-01-01

    1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely ...

  4. Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy.

    Science.gov (United States)

    Jellish, W S; Thalji, Z; Brundidge, P K; Tempelhoff, R

    1996-01-01

    Long-term chronic anticonvulsant therapy produces a resistance to the effects of all nondepolarizing neuromuscular blocking agents studied to date. Since the metabolism of mivacurium is unique among the nondepolarizing neuromuscular blocking agents, the effect of anticonvulsants on its recovery parameters was examined. Forty-five patients were separated into three groups based on the number of chronic anticonvulsant medications the subjects were taking: subjects in group 1, the control group, took no anticonvulsant medication; group 2 subjects took one medication; and group 3 subjects took two medications. Mivacurium, 0.15 mg/kg i.v., was administered after induction of general anesthesia with thiopental sodium, 4-6 mg/kg, and fentanyl 2-4 micrograms/kg i.v. Maintenance anesthesia consisted of N2O in O2. 0.2-0.3% end-tidal isoflurane, and a fentanyl infusion. The evoked compound electromyograph (ECEMG) of the adductor pollicis-brevis muscle was measured for time of onset, T-1 (time at which ECEMG signal reaches 5, 25, 50, and 75% of baseline), TR (TOF ratio), and recovery index. T-1 at 25% was 18.2 +/- 1.8, 20.7 +/- 1.9, and 21.5 +/- 1.4 min for groups 1, 2, and 3, respectively, with TR at 25% being 23.7 +/- 2.3, 26.9 +/- 2.4, and 27.3 +/- 2.3 min. No significant differences were noted in neuromuscular recovery between groups at any time point. These results fail to demonstrate the resistance to the nondepolarizing neuromuscular blockade of mivacurium that has been observed with other nondepolarizing agents. PMID:8719185

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

    OpenAIRE

    Gamal A. Soliman; Hasan Yusufoglu; Irem Tatli-Çankaya; Abdel-Rahman, Rehab F; Serap Aarabaci Anul; Galip Akaydn

    2016-01-01

    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, e...

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum.

    Science.gov (United States)

    Challal, Soura; Buenafe, Olivia E M; Queiroz, Emerson F; Maljevic, Snezana; Marcourt, Laurence; Bock, Merle; Kloeti, Werner; Dayrit, Fabian M; Harvey, Alan L; Lerche, Holger; Esguerra, Camila V; de Witte, Peter A M; Wolfender, Jean-Luc; Crawford, Alexander D

    2014-10-15

    Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay-guided microfractionation to rapidly identify novel bioactive small molecules of natural origin. PMID:25127088

  9. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants.

    Science.gov (United States)

    Tempelhoff, R; Modica, P A; Jellish, W S; Spitznagel, E L

    1990-12-01

    Previous studies have demonstrated that, with the exception of atracurium, resistance to the neuromuscular blocking effects of various muscle relaxants develops in patients receiving anticonvulsant therapy. We studied the effects of 0.5 mg/kg IV atracurium in 53 neurosurgical patients: 21 nonepileptic patients receiving no anticonvulsant therapy (MED = 0); 14 epileptic patients treated with carbamazepine for years (MED = 1); and 18 epileptic patients treated with carbamazepine plus either phenytoin or valproic acid for years (MED = 2). The evoked compound electromyogram of the adductor pollicis brevis was recorded, and results were analyzed using analysis of covariance, with weight and age as covariables. The onset time was not significantly different among the three groups. Times for recovery of baseline and train-of-four responses to stimuli were significantly shorter in the MED = 1 and MED = 2 groups than in control patients (MED = 0). The recovery index (time between 25% and 75% recovery of baseline electromyogram values) was progressively shorter in the three groups (MED = 0: 8.02 min; MED = 1: 5.93 min; MED = 2: 1.96 min; P less than 0.001). This study demonstrates that atracurium, when used on epileptic patients requiring long-term (that is, years of) anticonvulsant therapy, has a shorter duration of action than when used in nonepileptic patients. PMID:2240640

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Anticonvulsants in the treatment of aggression in the demented elderly: an update

    Directory of Open Access Journals (Sweden)

    Gonzalez-Pinto Ana

    2009-06-01

    Full Text Available Abstract Introduction Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity. Methods Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate. Results To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate. Conclusion So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.

  12. Spectrum of Side Effects of Anticonvulsants in Patients with Brain Tumours

    Directory of Open Access Journals (Sweden)

    Benit CP

    2012-01-01

    Full Text Available Seizures are a common manifestation in patients with brain tumours, and most patients need anticonvulsants. Apart from seizure control, the risk of side effects makes the proper choice of anticonvulsants a major concern. Toxicities not only exist as common side effects, but also appear as drug-drug interactions, neurotoxicities, and other organ dysfunctions. One reason for interactions is the use of the classical anti-epileptic drugs (AED, phenobarbital (PB, phenytoin (PHT, and carbamazepine (CBZ. Large differences in dose regimens with concomitant chemotherapy reflect the potency of these effects. Although valproic acid (VPA can be beneficial to prevent tumour growth, it may lead to bone marrow suppression and other toxicities because of its enzyme-inhibiting properties. Another noteworthy side effect are skin reactions, like erythema multiforme, which occasionally develops during radiation. Although this side effect is rare, it can be life-threatening. Many anti-epileptic drugs can have extra toxic effects with existing organ dysfunction, like bone-marrow suppression or liver abnormalities, this applies particularly for PB, PHT, CBZ, and VPA. Existing clinical or subclinical signs of brain damage secondary to space-occupying tumoural effects or the sequelae of previous neurosurgery, radio-, and chemotherapy enhance the chances of neurotoxicity. Besides, the intake of anticonvulsants itself and their total number strongly contribute to cognitive dysfunction. As neurocognitive decline interferes with quality of life, such changes may substantially affect daily activities of patients and their family members. The multitude of co-therapies applied with brain tumours contributes to a myriad of side effects that are almost impossible to unravel, as drugs and other therapies used can have aggravating or counteracting effects on each other. Knowledge of individual anticonvulsants and anticipation of toxicity including the recognition of already

  13. Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2.

    Science.gov (United States)

    Payandemehr, Borna; Ebrahimi, Ali; Gholizadeh, Ramtin; Rahimian, Reza; Varastehmoradi, Bardia; Gooshe, Maziar; Aghaei, Hossein Nayeb; Mousavizadeh, Kazem; Dehpour, Ahmad Reza

    2015-03-01

    Cannabinoid and PPAR receptors show well established interactions in a set of physiological effects. Regarding the seizure-modulating properties of both classes of receptors, the present study aimed to evaluate the roles of the PPAR-gamma, PPAR-alpha and CB1 receptors on the anticonvulsant effects of WIN 55,212-2 (WIN, a non selective cannabinoid agonist). The clonic seizure thresholds after intravenous administration of pentylenetetrazole (PTZ) were assessed in mice weighing 23-30 g. WIN increased the seizure threshold dose dependently. Pretreatment with pioglitazone, as a PPARγ agonist, potentiated the anticonvulsant effects of WIN, while PPARγ antagonist inhibited these anticonvulsant effects partially. On the other hand PPARα antagonist reduced the anticonvulsant effects of WIN significantly. Finally the combination of CB1 antagonist and PPARα antagonist could completely block the anticonvulsant properties of WIN. Taken together, these results show for the first time that a functional interaction exists between cannabinoid and PPAR receptors in the modulation of seizure susceptibility. PMID:25448777

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Efficiency of combined carbamazepine and nootropics to reduce side effect of anticonvulsant therapy

    Directory of Open Access Journals (Sweden)

    Ivanov A.V.

    2013-01-01

    Full Text Available Background. The high rate of epileptic disease spreading determines the need of antiepileptic drugs investigation. Carbamazepine, being one of the most effective anticonvulsant drugs, has a wide spectrum of common side effects, and one of the supposed ways to solve this problem is to combine carbamazepine with nootrops. The possibility of the combined anticonvulsant and nootropic therapy still needs further researches. Objective. To study the efficiency of the combined carbamazepine and nootrops use in the experiment on rats and mice to reduce the side effects of anticonvulsant therapy in the form of impaired cognitive brain function and performance. Methods. The research was conducted on 50 white rats and 30 white mice divided randomly in 5 groups: group 1 received carbamazepine 40mg/kg; group 2 – carbamazepine 40 mg/kg + pyracetam 500 mg/kg; group 3 – carbamazepine 40 mg/kg + citicoline 500 mg/kg; group 4 – carbamazepine 40 mg/kg + memantine 10 mg/kg; group 5 – intact animals (control group. The myorelaxing effects of the therapy, physical working capacity, neurotoxity of the drugs were estimated on the 4th day of nootrops administration and 30 minutes after single carbamazepine administration. Histological examination of the brain specimens was performed; the doses of carbamazepine used in morphological study were 40 mg/kg, 150 mg/kg and 720 mg/kg intragastrally. Results. Administration of carbamazepine occurs moderate morphological changes of brain tissue caused by a reaction on the part of the microvasculature, the severity of which depends on the dose of the drug. Conclusion. The most effective combinations that remove the central side effects of carbamazepine are carbamazepine + gliatilin and carbamazepine + citicoline.

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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....

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

    OpenAIRE

    Abhijit Kadam; Sampada Jangam; Rajesh Oswal

    2011-01-01

    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 calc...

  19. 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.

  20. 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. PMID:25684626

  1. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

    International Nuclear Information System (INIS)

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [3H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [3H]BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of [3H]BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that [3H]BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations

  2. 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.

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

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    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.

  4. Effect of anticonvulsant drugs on (35S)t-butylbicyclophosphorothionate binding in vitro and ex vivo

    International Nuclear Information System (INIS)

    Using several concentrations of eight anticonvulsant drugs in clinical use (carbamazepine, clonazepam, phenytoin, phenobarbital, ethosuximide, primidone, sodium valproate, and D,L-γ-vinyl GABA), we studied their abilities in vitro to displace (35S)t-butylbicyclophosphorothionate (35S-TBPS) from its binding site in a homogenate of rat brain. Thereafter ethosuximide (150 mg/kg), phenobarbital (30 mg/kg), clonazepam (0.3 mg/kg), or phenytoin (100 mg/kg) was injected intraperitoneally into rats for 16-20 days; and the effect of drug administration on 35S-TBPS binding was studied in the cortex and hippocampus ex vivo. Phenobarbital (100 μM, P35S-TBPS binding in vitro by 10-16%. After drug administration of phenobarbital (concentration in plasma 168 μM), the number of binding sites decreased and the binding affinity (p35S-TBPS binding in vitro at the concentration analogous to therapeutic plasma levels or ex vivo at the dose used. These results suggest that the use of phenobarbital may modulate the TBPS binding site, but the role of the present findings in the anticonvulsant action of phenobarbital needs to be further studied. (author)

  5. Convulsant and anticonvulsant actions of agonists and antagonists of group III mGluRs.

    Science.gov (United States)

    Ghauri, M; Chapman, A G; Meldrum, B S

    1996-06-17

    Group III metabotropic glutamate receptors (mGluR4, 6, 7, 8) are negatively coupled to adenylate cyclase and, when activated presynaptically, decrease the release of glutamate and GABA. We have used intracerebroventricular injections of agonists and antagonists believed to act selectively on these receptors to study the pro- or anti-convulsant effects of mGluR III activation in nonepileptic (Swiss-Webster) and epileptic (DBA/2) mice. In both mouse strains the prototypic agonists L-2-amino-4-phosphonobutanoate (LAP4) and L-serine-O-phosphate are proconvulsant. The supposed antagonists (S)-2-methyl-2-amino-4-phosphonobutanoate (MAP4) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG), have a predominantly proconvulsant effect. (S)-alpha-methyl-3-carboxyphenylalanine, which is a potent and selective antagonist for LAP4 in the cortex, is anticonvulsant in DBA/2 mice and decreases the convulsant effect of N-methyl-D-aspartate, 3,5-dihydroxyphenylglycine, LAP4 and MPPG in Swiss-Webster mice. These data suggest that reduced inhibitory transmission may be more significant than reduced synaptic release of glutamate following group III mGluR activation. PMID:8856700

  6. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

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    Masoumeh Asgarshirazi

    2015-06-01

    Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

  7. EVALUATION OF ANTICONVULSANT ACTIVITY OF ALCOHOLIC EXTRACT OF BENINCASA HISPIDA (THUNB COGN. FRUIT EXTRACTS

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    S K Nimbal

    2011-12-01

    Full Text Available Epilepsy is a common neurological condition, affecting 0.5 to 1% of the population worldwide. According to the Sanskrit texts, Benincasa Hispida fruit is useful in insanity, epilepsy, constipation, piles dyspepsia and other nervous diseases; fresh juice is given either with sugar or as an adjunct to other medicines for these diseases. In this work, the anticonvulsant properties of alcoholic extract of Benincasa Hispida studied on maximal electroshock test (MEST, pentylenetetrazole and strychnine-induced seizures model in mice. The oral acute toxicity values (LD50 in mice were also evaluated. The alcoholic extract of Benincasa Hispida of protected animals against maximal electroshock-induced convulsion and reduced the mean recovery time from convulsion. The alcoholic extract of Benincasa Hispida had a also shows anticonvulsant activity against pentylenetetrazole-induced convulsion and protect mice against strychnine-induced convulsions. These results suggest that the ethanolic extract of Benincasa Hispida contains pharmacologically active substance(s like triterpenoids, flavonoids, glycosides and steroids, which may be valuable in the treatment of convulsive disorders, especially Grand mal epilepsy.

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

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    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.

  9. 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.

  10. Evaluation of the Anticonvulsant Activity of Zanthoxylum capense (Thunb. Harv. (Rutaceae in Mice

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    G.J. Amabeoku

    2010-01-01

    Full Text Available The anticonvulsant activity of Zanthoxylum capense (Thunb. Harv. (Rutaceae was investigated by studying the effects of the leaf methanol and aqueous extracts on seizures induced by pentylenetetrazole, bicuculline, picrotoxin, N-methyl-DL-aspartic acid and strychnine in mice. Both methanol and aqueous extracts of Z. capense significantly antagonized (pZ. capense significantly antagonized (p50 value obtained following oral administration of both the leaf aqueous and methanol extracts of Z. capense was above 3200 mg kg-1 and that obtained after intraperitoneal administration was 283.6 mg kg-1. The phytochemical analysis of the plant species revealed the presence of alkaloids, triterpene steroids, reducing sugars, saponins, tannins and quinones. The data obtained indicate that the leaf methanol and aqueous extracts of Z. capense have anticonvulsant activity which may probably involve both GABAergic, glutaminergic and glycinergic mechanisms. The relatively high LD50 value obtained following oral administration of the plant extract shows that it is non-toxic and /or safe in mice.

  11. Synthesis and Anticonvulsant Activity of Various Mannich and Schiff Bases of 1,5-Benzodiazepines

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    Surendra N. Pandeya

    2012-01-01

    Full Text Available Benzodiazepines have a various behavioral effects in addition to their anxiolytic action. There is every reason to believe that the BZ/GABA receptor complex is involved in these effects, since GABAmimetic manipulations modify the effect of BZ in tests of convulsive activity, motor function, and appetitive behavior. 1,5-Benzodiazepines are biologically important molecules and are extensively used clinically as analgesic, hypnotic, sedative, and antidepressive agents. Hence, 1,5-Benzodiazepines were synthesized by condensation of o-phenylenediamine and ketones, for example, cyclohexanone and acetone in presence of sulfated zirconia (catalyst. Mannich bases were synthesized with acetophenone, p-nitroacetophenone, p-chloroacetophenone, and formaldehyde. Schiff bases were synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p-chlorophenylsemicarbazide in the presence of glacial acetic acid. All the synthesized compounds were characterized by 1H NMR and IR spectral analyses. All the synthesized derivatives were evaluated at the dose of 30 mg/kg b.w for anticonvulsant activity by isoniazid induced convulsion model, and the compounds NBZD-3 and NBZD-8 were found to be the most active among all compounds. Among all the synthesized derivatives, compounds NBZD-13 and NBZD-17 were found to be the most active among all compounds using thiosemicarbazide induced model. Although NBZD-8, NBZD-10, and NBZD-18 are the compounds which had shown good anticonvulsant activity and have an advantage over that, they were not sedative.

  12. 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.

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

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    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

  14. SYNTHESIS AND BIOLOGICAL EVALUTION OF 3-CHLORO 2- METHYL PHENYL CARBAMOYL SUBSTITUTED SEMICARBAZONE DERIVATIVES AS POTENTIAL ANTICONVULSANT AGENTS

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    Laxmi Banjare

    2012-01-01

    Full Text Available A series of 3- chloro 2- methyl phenyl carbamoyl substituted semicarbazones (4-21 was synthesized and evaluated for anticonvulsant and CNS activities. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximalelectroshock seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration . . Aryl semicarbazides have also been reported to display excellent anticonvulsant activity in mice and rats . In terms of interaction at the binding site, as proposed previously by Dimmock et al. the pharma-cophoric elements were thought to be a lipophilic aryl ring and hydrogen bonding semicarbazone moiety. The attach- ment of a second aryl ring designated as the distal ring to the proximal aryl ring to increase the van der Waal’s bonding at the binding site and to increase potency have also been reported. Substitutions in the aryl ring by halogens have been found to increase potency in the MES screen .

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

    International Nuclear Information System (INIS)

    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

  16. 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

  17. Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

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    S Sardari

    2011-10-01

    Full Text Available "n  Background and purpose of the study: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ and maximal electroshock (MES seizure tests. "n  Methods: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p. and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p. or tonic seizures induced by MES (50 mA, 50Hz, 1sec were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. "n  Results: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. "n  Major conclusion: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.

  18. Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice.

    Science.gov (United States)

    Mosińska, Paula; Socała, Katarzyna; Nieoczym, Dorota; Laudon, Moshe; Storr, Martin; Fichna, Jakub; Wlaź, Piotr

    2016-07-01

    The anticonvulsant activity of melatonin (MLT) have been tested in several in vivo models and against different convulsive stimuli. Although MLT exerts high affinity towards melatonin receptors (MTs), the potential usefulness in the treatment of epilepsy is limited mainly due to its short half-life. Therefore, the purpose of the present study was to compare the anticonvulsant properties of novel MT agonists Neu-P11 and Neu-P67 with MLT in mice. The anticonvulsant activity of tested compounds was evaluated in pentylenetetrazole-(PTZ) and electrically-induced convulsions. The effect of studied compounds on motor coordination and skeletal muscular strength in mice was assessed in the chimney test and grip test, respectively. The locomotor activity after administration of the tested compounds was also evaluated. In the MEST and 6Hz tests, only MLT (50 and 100mg/kg, i.p.) significantly increased the seizure threshold. The i.p. administration of MLT (100mg/kg) and Neu-P67 (200mg/kg) resulted in a significantly elevated PTZ seizure threshold for forelimbs tonus. The compounds did not affect muscle strength. No alterations in motor coordination were noted. However, the locomotor activity was significantly decreased after administration of all tested compounds. Our study confirms the anticonvulsant potency of MLT and shows that novel synthetic MT agonists Neu-P11 and Neu-P67 have no effect on epileptic seizures in mice. Our data suggest that the activation of MT can be used in the treatment of seizures, but further pharmacological characterization is needed to understand the anticonvulsant activity of MLT and to design efficient MT-targeting antiepileptic drugs. PMID:27016427

  19. 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. PMID:26018871

  20. Anticonvulsant treatments of dysphoric mania: a trial of gabapentin, lamotrigine and carbamazepine in Iran

    Directory of Open Access Journals (Sweden)

    Naghmeh Mokhber

    2008-05-01

    Full Text Available Naghmeh Mokhber1, Carol J Lane2, Mohamad R Azarpazhooh3, Elham Salari4, Reza Fayazi5, Mohamad T Shakeri6, Allan H Young71Assistant Professor of Psychiatry, 3Assistant Professor of Neurology, 4Mashhad Department of Forensic Psychiatry, 5Assistant Professor of Psychiatry, 6Assistant Professor of Statistics, Mashhad University of Medical Science, Mashhad, Iran; 2Department of Psychiatry, University of British Columbia, Vancouver, Canada7Abstract: The treatment of dysphoric mania is challenging given the need to treat symptoms of both depression and mania simultaneously without provoking any clinical exacerbation. The newer antiepileptic drugs such as gabapentin, lamotrogine, and carbamazepine are often used as adjuncts to either lithium or valproic acid in the treatment of bipolar disorder. We decided to undertake a monotherapy trial because previous evidence suggested mixed states may be more responsive to anticonvulsants than more traditional antimanic agents. 51 patients with a DSM IV diagnosis of dysphoric mania were randomized to three groups comprising gapbapentin, lamotrogine or carbamazepine and followed for 8 weeks. Psychiatric diagnosis was verified by the structural clinical interview for the DSM-IV (SCID. The MMPI-2 in full was used to assess symptoms at baseline and 8 weeks. All three groups showed significant changes in MMPI-2 scores for depression and mania subscales. Gabapentin showed the greatest change in depression symptom improvement relative to lamotrogine and carbamazepine, respectively. Although manic symptoms improved overall, there were no differences between groups in the degree of manic symptom improvement.Keywords: dysphoric mania, manic-depression, depression, anticonvulsant, mood stabilizer

  1. Anticonvulsant and anxiolytic activity of the leaf aqueous and ethanolic extracts of Melanthera scandens in a rat model

    Science.gov (United States)

    Twinomujuni, Silvano S.; Oloro, Joseph; Alele, Paul E.

    2016-01-01

    Modern drug therapy of epilepsy is complicated by the inability of drugs to control seizures in some patients and side effects that range in severity from minimal impairment of the central nervous system to death from aplastic anemia or hepatic failure. Medicinal plants used in traditional medicine for the treatment of epilepsy have been scientifically shown to possess promising anticonvulsant activities in animal models for screening for anticonvulsant activity and can be a source of newer anticonvulsants. The aim of this study was to investigate the preliminary phytochemical properties, anticonvulsant and anxiolytic activities of Melanthera scandens aqueous and ethanolic extracts. Phytochemicals from the aqueous and ethanolic extracts were screened by standard methods. Anticonvulsant activity was evaluated against pentylenetetrazol (PTZ)-induced seizure model in rats. The effect of the extract at oral dose levels of 250, 500 and 1000 mg/kg was evaluated in an experimental rat model, using diazepam (5 mg/kg) as positive control. Anxiolytic activity was performed using elevated plus maze method. Phytochemical screening revealed that M. scandens extracts contain carbohydrates, flavonoids, saponins, glycosides, tannins, terpenoids, phenols and phytosterols. The aqueous extract at a dose of 500 mg/kg significantly increased seizure latency (P=0.0023), while the ethanolic extract did not have a significant effect on seizure latency. Both extracts significantly reduced the seizure severity (P= 0.0155), and provided up to 100% protection against PTZ induced death at 1000 mg/kg. Both extracts had no significant effect on the duration of PTZ induced seizures. Both extracts were found to increase the number of entries and the time spent in the open arms of the maze at a dose of 250 mg/kg, indicating anxiolytic activity, which was not seen at higher doses (500 and 1000 mg/kg). The total numbers of entries into the closed arm were significantly reduced at 500 and 1000 mg

  2. Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents.

    Science.gov (United States)

    Mohammadi-Khanaposhtani, Maryam; Shabani, Mohammad; Faizi, Mehrdad; Aghaei, Iraj; Jahani, Reza; Sharafi, Zainab; Shamsaei Zafarghandi, Narges; Mahdavi, Mohammad; Akbarzadeh, Tahmineh; Emami, Saeed; Shafiee, Abbas; Foroumadi, Alireza

    2016-04-13

    A number of acridone-based oxadiazoles 11a-n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 11l with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAA receptor confirms possible binding of compound 11l with BZD receptors. PMID:26890115

  3. 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. PMID:26902360

  4. Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives

    Directory of Open Access Journals (Sweden)

    Xinghua Zhen

    2015-07-01

    Full Text Available A new series of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ-evoked convulsion model and antidepressant activity in the forced swimming test (FST model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.

  5. Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives.

    Science.gov (United States)

    Zhen, Xinghua; Peng, Zhou; Zhao, Shuilian; Han, Yan; Jin, Qinghao; Guan, Liping

    2015-07-01

    A new series of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ)-evoked convulsion model and antidepressant activity in the forced swimming test (FST) model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q) showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine. PMID:26579465

  6. 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

    The endogenous neuropeptide galanin is ubiquitously expressed throughout the mammalian brain. Through the galanin receptors GalR1-3, galanin has been demonstrated to modulate both glutamatergic and GABAergic neurotransmission, and this appears to be important in epilepsy and seizure activity....... Accordingly, galanin analogues are likely to provide a new approach to seizure management. However, since peptides are generally poor candidates for therapeutic agents due to their poor metabolic stability and low brain bioavailability, a search for alternative strategies for the development of galanin......-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...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Evaluation of anticonvulsant activity of ACE inhibitors (imidapril and quinapril) in experimentally induced animal models of epilepsy

    OpenAIRE

    VH, Pushpa; Poornima R.; HL, Kalabharathi; AM, Satish

    2016-01-01

    Background: Epilepsy is a chronic neurological disorder characterized by an enduring predisposition to generate seizures, may be associated with emotional and cognitive dysfunction. Objective of this study was to evaluate and compare the anticonvulsant activity of different doses of imidapril and quinapril in animal models of epilepsy. Methods: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: control (R.O-10 ml/kg), standard-sodium valproate (40 mg/kg), Q1...

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

    OpenAIRE

    Patil, Pravin O.; Sanjay B. Bari

    2016-01-01

    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 ...

  10. Comparison of anticonvulsant effect of competitive non-NMDA and noncompetitive NMDA receptor antagonists in adult rats

    Czech Academy of Sciences Publication Activity Database

    Lojková, Denisa; Živanovič, Dragana; Mareš, Pavel

    -, - (2005), s. 160-160. [Conference of the Czech Neuroscience Society /5./, The Annual Meeting of the Network of European Neuroscience Institutes. 19.11.2005-21.11.2005, Prague] R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : anticonvulsant effect * non-NMDA- receptor antagonist * NMDA receptor antagonist * rats Subject RIV: ED - Physiology

  11. Influence of sildenafil on the anticonvulsant action of selected antiepileptic drugs against pentylenetetrazole-induced clonic seizures in mice

    OpenAIRE

    Nieoczym, Dorota; Socała, Katarzyna; Łuszczki, Jarogniew J.; Czuczwar, Stanisław J; Wlaź, Piotr

    2012-01-01

    The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on c...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Anticonvulsant action of gamma-irradiated diazepam with correlation to certain brain amino acids and electrocorticogram activity in experimental animals

    International Nuclear Information System (INIS)

    The effect of sterilization by gamma irradiation (215 KGy) of diazepam on is anticonvulsant action, on norma and depleted cerebral gamma aminobutyric acid (GABA), on glutamic acid, as well as electrocorticogram activity (ECOG) was determined in the experimental animals. For the evaluation of the anticonvulsant action of either diazepam (D) or irradiated diazepam (ID), pentyl ene tetrazole seizure test, was used and the protective dose 50 (PD50) was determined in adult male mice. GABA, the main central inhibitory transmitter which is implicated in the mechanism of the anticonvulsant action of D and its precursor glutamic acid, were electrophoretically separated and spectrophotometrical evaluated. Moreover, brain electrical activity was recorded using an electroencephalograph apparatus. Although the PD50 of ID as well the effect on normal brain cerebral GABA and glutamic acids did not differ significantly from that of D, yet there was certain variabilities. Thus, the effect of D was about 4 times more potent than the ID on elevating depleted cerebral GABA. Also, electrocorticogram records demonstrated that D produced a slight inhibition while ID induced a decrease in B rhythm with remarkable in the amplitude of ECOG waves. The same pattern of effects were obtained when D or ID were used in combination with INH (250 mg kg-1). 1 tab. 1 fig

  14. Effect of anticonvulsant drugs on (/sup 35/S)t-butylbicyclophosphorothionate binding in vitro and ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pitkaenen, A.; Riekkinen, P.J.; Saano, V.; Tuomisto, L.

    1987-01-01

    Using several concentrations of eight anticonvulsant drugs in clinical use (carbamazepine, clonazepam, phenytoin, phenobarbital, ethosuximide, primidone, sodium valproate, and D,L-..gamma..-vinyl GABA), we studied their abilities in vitro to displace (/sup 35/S)t-butylbicyclophosphorothionate (/sup 35/S-TBPS) from its binding site in a homogenate of rat brain. Thereafter ethosuximide (150 mg/kg), phenobarbital (30 mg/kg), clonazepam (0.3 mg/kg), or phenytoin (100 mg/kg) was injected intraperitoneally into rats for 16-20 days; and the effect of drug administration on /sup 35/S-TBPS binding was studied in the cortex and hippocampus ex vivo. Phenobarbital (100 ..mu..M, P<0.001), ethosuximide (500 ..mu..M, P<0.001), and phenytoin (40 ..mu..M, P<0.001) decreased the specific /sup 35/S-TBPS binding in vitro by 10-16%. After drug administration of phenobarbital (concentration in plasma 168 ..mu..M), the number of binding sites decreased and the binding affinity (p<0.05) in the cortex increased. Other anticonvulsants did not modulate /sup 35/S-TBPS binding in vitro at the concentration analogous to therapeutic plasma levels or ex vivo at the dose used. These results suggest that the use of phenobarbital may modulate the TBPS binding site, but the role of the present findings in the anticonvulsant action of phenobarbital needs to be further studied.

  15. Preliminary Anticonvulsant and Toxicity Screening of Substituted Benzylidenehydrazinyl-N-(6-substituted benzo[d]thiazol-2-ylpropanamides

    Directory of Open Access Journals (Sweden)

    Ruhi Ali

    2014-01-01

    Full Text Available Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidenehydrazinyl-N-(substituted benzo[d]thiazol-2-yl-propanamides were synthesized with aromatic hydrophobic aryl ring (A, NH–C=O as hydrogen bonding domain (HBD, nitrogen atom as electron donor (D, and phenyl as distal aryl ring (C. Synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo anticonvulsant screening (phase I was performed by two most adopted seizure models, maximal electroshock seizure (MES and subcutaneous pentylenetetrazole (scPTZ. Based on anticonvulsant screening results, two compounds, 5h and 5p, were found to be most active; they exhibited activity comparable to standard drugs phenytoin (PHY and carbamazepine (CBZ. These active compounds were subjected to phase II and phase III screening, where they displayed much higher protective index (PI in comparison to the standard drugs. In phase IV screening, the bioavailability of active compounds was assessed on oral administration. Further, preliminary safety profiles of 5h and 5p were evaluated by the neurotoxicity testing and liver enzyme estimation.

  16. Lysine and pipecolic acid and some of their derivatives show anticonvulsant activity, and stimulation of benzodiazepine receptor activity

    International Nuclear Information System (INIS)

    Benzodiazepines are one of the most widely prescribed drugs in the treatment of anxiety, epilepsy and muscle tension. The natural products lysine and pipecolic acid known to be present in the animal, plant and microorganism, have been shown to be anticonvulsant against pentetrazol (PTZ)-induced seizures in mice. Methyl and ethyl esters of L-lysine and the N-isopropanol derivative of pipecolic acid appear to increase the anticonvulsant potency of the parent compounds, presumably due to their increase in hydrophobicity. Lysine and pipecolic acid showed significant stimulation of specific [3H]flunitrazepam (FZ) binding to mouse brain membranes. This stimulation was enhanced by chloride ions and stereospecific with L-isomer having higher effect. The dose-dependent anticonvulsant activity of lysine and pipecolic acid, and their stimulation of [3H]FZ binding appear to be correlated. The antiepileptic activity lysine, pipecolic acid and their derivatives therefore may be mediated through the γ-aminobutyric acid-benzodiazepine receptor complex

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

    Directory of Open Access Journals (Sweden)

    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

  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. 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.

  20. ANXIOLYTIC AND ANTICONVULSANT ACTIVITY OF ALCOHOLIC EXTRACT OF HEART WOOD OF CEDRUS DEODARA ROXB IN RODENTS

    Directory of Open Access Journals (Sweden)

    GL VISWANATHA,K NANDAKUMAR, SHYLAJA H

    2013-09-01

    Full Text Available The present study was undertaken to evaluate the anxiolytic and anti-convulsant activityof the alcoholic extract of heart wood of Cedrus deodara (ALCD. 50,100 and 200 mg/kg ofalcoholic extract of Cedrus deodara (ALCD were tested for its anxiolytic and anticonvulsantactivity. Elevated plus maze model (EPM, Actophotometre, Light-dark model were used fortesting anxiolytic activity and Pentylene tetrazole (PTZ induced convulsions and Maximalelectro shock (MES induced convulsions models in mice were used for the assessment of itsanticonvulsant activity, Pretreatment with ALCD and estimation of GABA in rat brain tissuesalso performed to study the effect of ALCD (30, 100 mg/kg on GABA levels of brain. InActophotometre test, higher doses (100 and 200mg/kg of ALCD has showed significant CNSdepression by reducing locomotor activity in mice. In EPM the 100 and 200mg/kg of ALCDhas increased the time spent in the open arm and decreased time spent in the closed arm. InLight-dark model the 100 and 200mg/kg of ALCD has showed significant increase in the timespent in light zone when compare to the dark zone. In PTZ induced convulsions model 100 and200 mg/kg of ALCD has increased the onset of clonus and tonic seizures.

  1. Triazolines. 14. 1,2,3-Triazolines and triazoles, a new class of anticonvulsants. Drug design and structure-activity relationships.

    Science.gov (United States)

    Kadaba, P K

    1988-01-01

    Pioneering studies in our laboratories have led to the emergence of the delta 2-1,2,3-triazolines (4,5-dihydro-1H-1,2,3-triazoles) and the closely related 1H-1,2,3-triazoles as a unique family of anticonvulsant agents hitherto unknown. Unlike the traditional anticonvulsants, the dicarboximide moiety is absent from the traiazoline ring system. This paper examines the results of evaluation of several groups of 1-aryl-5-pyridyl-substituted triazolines and triazoles with particular reference to structure-activity relationships in each compound group as well as between compounds in the different groups and the 1,5-diaryl compounds. The Topliss manual approach for application fo the Hansch method is employed for the rational design of triazoline/triazole anticonvulsants. Anticonvulsant activity was determined, after intraperitoneal administration, in two standard seizure models in the mouse, the MES and scMet tests. Central nervous system toxicity was evaluated in the rotorod ataxia test. Analysis of structure-activity relationships using the Topliss scheme indicated a clear pi + sigma dependency in the 1-aryl-5-(4-pyridyl)triazolines while an adverse steric effect (Es) from 4-substitution appeared to be present in the 1-aryl-5-(3-pyridyl) compounds. A similar but strong steric effect dominated the structure-activity pattern of the 1-aryl-5-(4-pyridyl)triazoles, although a sigma dependency was more evident in the 1-aryl-5-(3-pyridyl)- and the 1,5-diaryltriazole series. No significant activity was observed among the 1-aryl-5-(2-pyridyl)triazolines, and although the respective triazoles were active, the parameter dependency was not clearly defined. Similarly, the 1,5-diaryltriazolines, as a group, showed no pronounced anticonvulsant activity. However, replacement of the 5-aryl with a pyridyl group, particularly a 4-pyridyl, led to highly enhanced anticonvulsant activity. In addition, oxidation of triazolines with no anticonvulsant activity yielded, as a rule, triazoles

  2. Triazolines. XXI: Preformulation degradation kinetics and chemical stability of a novel triazoline anticonvulsant.

    Science.gov (United States)

    Freeke Hamelijnck, M A; Stevenson, P J; Kadaba, P K; Damani, L A

    1992-04-01

    The effect of pH, temperature, and two buffer species (citric acid-phosphate and bicarbonate-carbonate) on the stability of 1-(4-chlorophenyl)-5-(4-pyridyl)-delta 2-1,2,3-triazoline (ADD17014; 1), a novel triazoline anticonvulsant, was determined by HPLC. One of the main degradation products of 1 at pH 7.0 was isolated by TLC and identified as the aziridine derivative by MS. Investigations were carried out over a range of pH (2.2-10.7) and buffer concentration [ionic strength (mu), 0.25-4.18] at 23 degrees C. The degradation followed buffer-catalyzed, pseudo-first-order kinetics and was accelerated by a decrease in pH and an increase in temperature. The activation energy for the degradation in citric acid-phosphate buffer (pH 7.0 and constant ionic strength mu at 0.54) was 12.5 kcal/mol. General acid catalysis was observed at pH 7.0 in citric acid-phosphate buffer. The salt effect on the degradation obeyed the modified Debye-Hückel equation well; however, the observed charge product (ZAZB) value (2.69) deviated highly from the theoretical value (1.0), perhaps because of the high mu values (0.25-4.18) of the solutions used. The stability data will be useful in preformulation studies in the development of a stable, oral dosage form of 1. PMID:1501079

  3. Anticonvulsant activity and toxicity of essential oil and methanolic extract of Zhumeria majdae Rech, a unique Iranian plant in mice.

    Science.gov (United States)

    Mandegary, Ali; Sharififar, Fariba; Abdar, Maryam; Arab-Nozari, Milad

    2012-12-01

    Drug-resistance and adverse effects of current drugs are the most obstacles in the treatment of epilepsy. In a plan for finding new natural anticonvulsant agents, we studied the anticonvulsant effects of essential oil (ZMEO) and methanolic extract (ZMME) of Zhumeria majdae in pentylene tetrazol (PTZ) and maximal electro-shock (MES) models in mice. Mice received different doses of ZMEO and ZMME, 30 min before induction of chemical and electrical convulsions. Neurotoxicity (movement toxicity and sedation) was evaluated using rota-rod test. The mortality was determined after 24 h following injection of different doses of the ZMEO and ZMME. The obtained results show that ZMEO dose-dependently protected mice from tonic convulsions induced by PTZ and MES with effective doses (ED(50)) of 0.26 (0.13-0.39) and 0.27 (0.17-0.37) ml/kg respectively. Toxic doses (TD(50)) in rota-rod test for ZMEO was 0.55 (0.42-0.70) ml/kg. ZMME at dose of 2 g/kg decreased tonic convulsions as much as 40 %. For ZMEO, TD(50) of 0.55 (0.45-0.69) ml/kg was obtained. ZMME significantly decreased the walking time in rota-rod test at dose of 2 g/kg. Lethal dose (LD(50)) of ZMEO was determined as 2.35 (1.98-2.65) ml/kg. ZMME showed about 34 % death of the animals at dose 5 g/kg. The essential oil of Z. majdae could be a good candidate for further anticonvulsive studies. PMID:22890979

  4. Mechanisms of anticonvulsant and sedative actions of the ethanolic stem-bark extract of Ficus sur Forssk (Moraceae) in rodents.

    Science.gov (United States)

    Ishola, Ismail O; Olayemi, Sunday O; Yemitan, Omoniyi K; Ekpemandudiri, Ngozi K

    2013-11-01

    Ficus sur Forssk (Moraceae) is used in traditional African medicine in the treatment of epilepsy, pain and inflammations. Anticonvulsant activity was investigated using picrotoxin (PTX), strychnine (SCN), isoniazid (INZ), pentylenetetrazole (PTZ) and N-methyl-D-aspartic acid NMDA models of convulsion. The phytochemical analysis of the extract revealed the presence of flavonoids, saponins, tannins, alkaloids and anthraquinone. Oral administration of Ficus sur, 1 h before intraperitoneal injection of chemical convulsants significantly (p uses of Ficus sur in the treatment of epilepsies; mechanisms of which could involve interaction with GABAergic, glycinergic, serotonergic and glutaminergic system barks. PMID:24511736

  5. 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. PMID:26776225

  6. 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.

  7. Evaluation of Anticonvulsive Effect of Magnesium Oxide Nanoparticles in Comparison with Conventional MgO in Diabetic and Non-diabetic Male Mice

    OpenAIRE

    Jahangiri, Leila; Kesmati, Mahnaz; H Najafzadeh

    2014-01-01

    Introduction Some studies showed that magnesium has anticonvulsive effect in some animal models. Despite of the availability of well-studied anticonvulsant drugs, this evaluation was not carried on new kind of magnesium supplement, magnesium oxide nanoparticles (nMgO). According to the association between magnesium and convulsion and high prevalence of seizure and epilepsy in diabetics, this study was designed to evaluate the effect of nMgO compared to conventional MgO (cMgO) on strychnine-in...

  8. 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.

  9. 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.

  10. 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. PMID:25337354

  11. Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.

    Science.gov (United States)

    Harrison, Patrick K; Sheridan, Robert D; Green, A Chris; Tattersall, John E H

    2005-08-22

    Seizures arising from acetylcholinesterase inhibition are a feature of organophosphate anticholinesterase intoxication. Although benzodiazepines are effective against these seizures, alternative anticonvulsant drugs may possess greater efficacy and fewer side-effects. We have investigated in the guinea-pig hippocampal slice preparation the ability of a series of anticonvulsants to suppress epileptiform bursting induced by the irreversible organophosphate anticholinesterase, soman (100 nM). Carbamazepine (300 microM), phenytoin (100 microM), topiramate (100-300 microM) and retigabine (1-30 microM) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 microM) and clomethiazole (100-300 microM) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 microM) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 microM) and gabapentin (100-300 microM) were without effect. These data suggest that several compounds, in particular clomethiazole, clozapine, felbamate, topiramate and retigabine, merit further evaluation as possible treatments for organophosphate poisoning. PMID:16054127

  12. Synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives as potent anticonvulsant agents.

    Science.gov (United States)

    Edayadulla, Naushad; Ramesh, Penugonda

    2015-12-01

    An efficient synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives has been achieved under aqueous medium for the first time in good to excellent yields. All the synthesized compounds were tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most broadly employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. Seven compounds 4a, 4d, 4f, 4h, 4o, 4p and 4q showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 4d showed the MES-induced seizures with ED50 value of 10.2 mg/kg and TD50 value of 288.6 mg/kg after intraperitoneal injection to mice, which provided compound 4d with a protective index (TD50/ED50) of 28.3 in the MES test. PMID:26519928

  13. Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications.

    Science.gov (United States)

    Landgrave-Gómez, Jorge; Mercado-Gómez, Octavio Fabián; Vázquez-García, Mario; Rodríguez-Molina, Víctor; Córdova-Dávalos, Laura; Arriaga-Ávila, Virginia; Miranda-Martínez, Alfredo; Guevara-Guzmán, Rosalinda

    2016-01-01

    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 (TRF) 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 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 h 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 increase in β-HB mediated by TRF

  14. 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

  15. 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. PMID:26441377

  16. Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols.

    Science.gov (United States)

    Gunia-Krzyżak, Agnieszka; Żesławska, Ewa; Słoczyńska, Karolina; Koczurkiewicz, Paulina; Nitek, Wojciech; Żelaszczyk, Dorota; Szkaradek, Natalia; Waszkielewicz, Anna M; Pękala, Elżbieta; Marona, Henryk

    2016-01-01

    Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock--MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as RM0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 Å--from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 Å--from the phenyl ring to the amide group, and 3.112 Å--from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). PMID:26560050

  17. Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task.

    Science.gov (United States)

    Tremblay, Melanie; Winstanley, Catharine A

    2016-11-01

    Impulsivity is a major component of mania in bipolar disorder (BD), and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are observed in some patients with temporal lobe epilepsy (TLE), and incidence of problem gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of BD. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioral aspect targeted by these drugs. This project explored the effect of the three anticonvulsant drugs currently also used as mood stabilizers- carbamazepine, valproate and lamotrigine on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). In this task, rats choose between four distinct, probabilistic reinforcement schedules. Sugar pellet profits are maximized by adopting a conservative strategy, avoiding tempting high-risk, high-reward options. Effects of the anticonvulsant agents were assessed on baseline performance and also in conjunction with amphetamine administration, in order to approximate a "mania-like" state. Carbamazepine appeared to slow processing speed, decreasing premature responses and increasing choice latency, whereas valproate and lamotrigine had no effect. When administered prior to amphetamine, lamotrigine was the only drug that failed to attenuate the pro-impulsive effect of the psychostimulant. Further studies looking at chronic administration of anticonvulsants may help us understand the impact of this medication class on decision-making and impulsivity in healthy rats and disease models. PMID:27515288

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

    OpenAIRE

    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 day...

  19. Triazolines XV. Anticonvulsant profile of ADD 17014, a potentially unique 1,2,3-triazoline antiepileptic drug, in mice and rats.

    Science.gov (United States)

    Kadaba, P K; Slevin, J T

    1988-01-01

    ADD 17014[1-(4-chlorophenyl)-5-(4-pyridyl) delta 2-1,2,3-triazoline], is a representative member of a hitherto unknown, structurally novel family of anticonvulsant agents. The anticonvulsant profile of ADD 17014 following intraperitoneal (i.p.) and oral administration in mice and rats was evaluated using a battery of well-standardized anticonvulsant tests and compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). The results indicate that ADD 17014 is effective in nontoxic i.p. doses in mice by the maximal electroshock seizure (MES), Metrazol (subcutaneous, s.c. Met), bicuculline (s.c. Bic) and picrotoxin (s.c. Pic) tests, but ineffective against strychnine-induced seizures; it is also effective after nontoxic oral doses in both mice and rats by the MES and s.c. Met tests. Protective indices (PI = TD50/ED50), calculated from i.p. data in mice, were highest for ADD 17014 by the s.c. Met (26.02) and s.c. Bic (93.93) tests; the PIs, after oral administration in mice and rats, were equal to or higher than those of the prototype agents. In vitro receptor binding studies of ADD 17014 and potential metabolites indicated no significant inhibitory activity except for the beta-amino alcohol, which displaced almost 93% of [3H]glutamate from the glutamate receptors, suggesting that ADD 17014 may be functioning as a prodrug and an excitatory amino acid antagonist. The overall results indicate that ADD 17014 is a relatively nontoxic agent that more closely resembles PB and VPA, with a broad and unique spectrum of anticonvulsant activity. PMID:3371287

  20. Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

    International Nuclear Information System (INIS)

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 ± 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 ± 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in

  1. 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

  2. Towards cheminformatics-based estimation of drug therapeutic index: Predicting the protective index of anticonvulsants using a new quantitative structure-index relationship approach.

    Science.gov (United States)

    Chen, Shangying; Zhang, Peng; Liu, Xin; Qin, Chu; Tao, Lin; Zhang, Cheng; Yang, Sheng Yong; Chen, Yu Zong; Chui, Wai Keung

    2016-06-01

    The overall efficacy and safety profile of a new drug is partially evaluated by the therapeutic index in clinical studies and by the protective index (PI) in preclinical studies. In-silico predictive methods may facilitate the assessment of these indicators. Although QSAR and QSTR models can be used for predicting PI, their predictive capability has not been evaluated. To test this capability, we developed QSAR and QSTR models for predicting the activity and toxicity of anticonvulsants at accuracy levels above the literature-reported threshold (LT) of good QSAR models as tested by both the internal 5-fold cross validation and external validation method. These models showed significantly compromised PI predictive capability due to the cumulative errors of the QSAR and QSTR models. Therefore, in this investigation a new quantitative structure-index relationship (QSIR) model was devised and it showed improved PI predictive capability that superseded the LT of good QSAR models. The QSAR, QSTR and QSIR models were developed using support vector regression (SVR) method with the parameters optimized by using the greedy search method. The molecular descriptors relevant to the prediction of anticonvulsant activities, toxicities and PIs were analyzed by a recursive feature elimination method. The selected molecular descriptors are primarily associated with the drug-like, pharmacological and toxicological features and those used in the published anticonvulsant QSAR and QSTR models. This study suggested that QSIR is useful for estimating the therapeutic index of drug candidates. PMID:27262528

  3. Effects of anticonvulsant drugs on the synthesis of DNA and protein by human bone marrow cells in vitro

    International Nuclear Information System (INIS)

    Suspensions of human bone marrow cells were incubated with various concentrations of phenobarbitone or phenytoin sodium for 2 h, and the effects of this incubation on the subsequent incorporation of 3H-thymidine and 3H-leucine into DNA and protein, respectively, were studied. Both drugs caused a depression of 3H-thymidine incorporation and this phenomenon was not prevented by the addition of 100 μg of pteroylglutamic acid, folinic acid or 5-methyltetrahydrofolate per ml of marrow culture. The lowest concentration of drug which caused a statistically significant depression of 3H-thymidine incorporation was 200μg per ml for phenobarbitone and 50 μg per ml for phenytoin sodium. Both phenobarbitone and phenytoin sodium also caused an increase in the incorporation of 3H-leucine at concentrations of 50 and 20 μg per ml., respectively, suggesting the possibility that a stimulation of protein synthesis within erythropoietic cells may play an important role in the development of anticonvulsant-induced macrocytosis. (authod)

  4. 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.

  5. Triazolines. XXIII. High-performance liquid chromatographic assay in rat blood for a novel triazoline anticonvulsant (ADD17014).

    Science.gov (United States)

    Stevenson, P J; Hamelijnck, M A; Kadaba, P K; Damani, L A

    1991-02-15

    A sensitive and specific high-performance liquid chromatographic (HPLC) method for the analysis of 1-(4-chlorophenyl)-5-(4-pyridyl)-delta 2-1,2,3-triazoline (ADD17014, I), a novel anticonvulsant agent, in rat blood is described. Compound I and the internal standard (dipyridamole) were extracted into diethyl ether (5 ml) from alkalinised blood (0.25 ml of blood plus 0.75 ml of pH 10.7 buffer), with extractability nearing 100% under these conditions. The assay is based on reversed-phase HPLC (25 cm x 0.46 cm I.D. Spherisorb 5-ODS) using a mobile phase of methanol-acetonitrile-McIlvaine's citric acid-phosphate buffer (pH 8.0, 0.005 M) (30:30:40, v/v) and ultraviolet detection at 290 nm. Calibration curves were linear and reproducible (correlation coefficient greater than 0.999). Measurement of I in rat blood (250 microliters sample size) was linear in the range 0-40 microgram/ml and the coefficient of variation was less than 5%. The minimum detectable level was about 0.1 microgram/ml; however, a larger blood sample size (1-2 ml) allowed measurement of levels as low as 10 ng/ml, especially for estimation of drug levels in samples withdrawn at later time points (24 h). PMID:2056006

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

    International Nuclear Information System (INIS)

    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 α1- but is a high efficacy positive allosteric modulator at α5-containing GABAA 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 a higher

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Lithium differs from anticonvulsant mood stabilizers in prefrontal cortical and accumbal dopamine release: role of 5-HT(1A) receptor agonism.

    Science.gov (United States)

    Ichikawa, Junji; Dai, Jin; Meltzer, Herbert Y

    2005-07-12

    Anticonvulsant mood stabilizers, e.g., valproic acid and carbamazepine, and atypical antipsychotic drugs (APDs), e.g., clozapine, quetiapine, olanzapine, risperidone, and ziprasidone, have been reported to preferentially increase dopamine (DA) release in rat medial prefrontal cortex (mPFC), an effect partially or fully inhibited by WAY100635, a selective 5-HT(1A) antagonist. These atypical APDs have themselves been reported to be effective mood stabilizers, although the importance of increased cortical DA release to mood stabilization has not been established. The purpose of the present study was to determine whether zonisamide, another anticonvulsant mood stabilizer, as well as lithium, a mood stabilizer without anticonvulsant properties, also increases prefrontal cortical DA release and, if so, whether this release is also inhibited by 5-HT(1A) antagonism. As with valproic acid and carbamazepine, zonisamide (12.5 and 25 mg/kg) increased DA release in the mPFC, but not the NAC, an increase abolished by WAY100635 (0.2 mg/kg). However, lithium (100 and 250 mg/kg) decreased DA release in the NAC, an effect also attenuated by WAY100635 (0.2 mg/kg). Lithium itself had no effect in the mPFC but the combination of WAY100635 (0.2 mg/kg) and lithium (100 and 250 mg/kg) markedly increased DA release in the mPFC. Furthermore, M100907 (0.1 mg/kg), a selective 5-HT(2A) antagonist, abolished this increase in DA release in the mPFC. These results indicate that not all mood-stabilizing agents but only those, which have anticonvulsant mood-stabilizing properties, increase DA release in the cortex, and that the effect is dependent upon 5-HT(1A) receptor stimulation. However, the combination of lithium and 5-HT(1A) blockade may result in excessive 5-HT(2A) receptor stimulation, relative to 5-HT(1A) receptor stimulation, both of which can increase prefrontal cortical DA release. PMID:15936730

  9. Anti-epileptogenic and anticonvulsant activity of L-2-amino-4-phosphonobutyrate, a presynaptic glutamate receptor agonist.

    Science.gov (United States)

    Abdul-Ghani, A S; Attwell, P J; Singh Kent, N; Bradford, H F; Croucher, M J; Jane, D E

    1997-05-01

    The protective effect of amygdaloid (focally administered) doses of the presynaptic metabotropic glutamate receptor agonist, L-2-amino-4-phosphonobutyrate (L-AP4) was tested on the development of electrical kindling and in fully kindled animals. L-AP4 inhibited epileptogenesis at 10 nmol in 0.5 microl buffer, by preventing the increase in both seizure score and afterdischarge duration. The effects were reversible after withdrawal of the drug, with all treated animals subsequently progressing to the fully kindled state at the same rate as control animals. The same concentration of the drug was also effective when injected into fully kindled animals. It significantly decreased the mean seizure score by 88% (P MPPG ((RS)-alpha-methyl-4-phosphonophenyl glycine) a selective antagonist of L-AP4 at glutamate pre-synaptic receptors inhibited the depressant effect of L-AP4 in a dose-dependent manner. MPPG (10 nmol) inhibited the antiseizure activity of L-AP4, whilst MPPG (40 nmol) reduced both the anti-epileptogenic and antiseizure activities of L-AP4. MPPG (40 nmol) by itself had no effect on generalized seizure activity, and it had no detectable influence on the normal rate of kindled epileptogenesis. During in vitro studies using a microsuperfusion method, L-AP4 inhibited depolarization-induced release of [3H]D-aspartate from rat cortical synaptosomes (IC50 125.1 microM) and decreased the depolarization-evoked uptake of 45Ca2+ in a dose-dependent manner. Both actions of L-AP4 were reduced by the selective antagonist MPPG. When applied alone MPPG (200 microM) had no detectable action on veratridine-evoked 45Ca2+ uptake by the synaptosomes. These results suggest the mechanisms by which presynaptically active glutamate receptor agonists block the development of the chronically epileptic state induced by electrical kindling, and indicate that their anticonvulsive activity is due to inhibition of presynaptic glutamate and/or aspartate release following blockade of presynaptic

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. 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.

  13. Rational drug design and the discovery of the delta2-1,2,3-triazolines, a unique class of anticonvulsant and antiischemic agents.

    Science.gov (United States)

    Kadaba, Pankaja K

    2003-10-01

    The delta(2)- 1,2,3- triazoline anticonvulsants (TRs) may be considered as representing a unique class of "built-in" heterocyclic prodrugs where the active "structure element" is an integral part of the ring system and can be identified only by a knowledge of their chemical reactivity and metabolism. Investigations on the metabolism and pharmacology of a lead triazoline, ADD17014 suggest that the triazolines function as "prodrugs" and exert their anticonvulsant activity by impairing excitatory amino acid (EAA) L-Glutamate (L-Glu) neurotransmission via a unique "dual-action" mechanism. While an active primary beta-amino alcohol metabolite from the parent prodrug acts as an N-methyl-D-aspartate (NMDA)/MK -801 receptor antagonist, the parent triazoline impairs the presynaptic release of L-Glu. Various pieces of theoretical reasoning and experimental evidence have led to the clucidation of the dual-action mechanism. Based on the unique chemistry of the triazolines, and their metabolic pathways, biotransformation products of TRs were predicted to be the beta-amino alcohols V and VA, the alpha-amino acid VI, the triazole VII, the aziridine VIII and the ketimine IX. In vivo and in vitro pharmacological studies of the TR and potential metabolites, along with a full quantitative urinary metabolic profiling of TR indicated the primary beta-amino alcohol V as the active species. It was the only compound that inhibited the specific binding of [3H]MK-801 to the MK-801 site, 56% at 10 micro M drug concentration, but itself had no anticonvulsant activity, suggesting TR acted as a prodrug. Three metabolites were identified; V was the most predominant (45.7 +/- 7.6) % of administered drug, with lesser amounts of VA, (17.3 +/- 5.1) % and very minor amounts of aziridine VIII (4.0 +/- 0.02)%. Since only VIII can yield VA, its formation indicated that the biotransformation of TR occurred, at least in part, through aziridine. No amino acid metabolite was detected, which implied that no

  14. Anticonvulsant and neuroprotective effect of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate is diminished when given after the onset of seizures induced by homocysteic acid in immature rats

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Druga, Rastislav; Otáhal, Jakub; Tsenov, Grygoriy; Haugvicová, Renata; Kubová, Hana

    2007. s. 87-87. [International Epilepsy Congress /27./. 08.07.2007-12.07.2007, Singapore] R&D Projects: GA ČR(CZ) GA309/05/2015 Institutional research plan: CEZ:AV0Z50110509 Keywords : group II mGluRs * anticonvulsant action * homocysteic acid Subject RIV: ED - Physiology

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

    International Nuclear Information System (INIS)

    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 LD50 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 × LD50), 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 LD50 of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD50 soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after soman, blocked seizures.

  16. 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

  17. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    Science.gov (United States)

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  18. 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

  19. Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats

    Directory of Open Access Journals (Sweden)

    Xu Wen

    2010-08-01

    Full Text Available Abstract Background Temporomandibular disorders (TMDs are characterized by persistent orofacial pain and have diverse etiologic factors that are not well understood. It is thought that central sensitization leads to neuronal hyperexcitability and contributes to hyperalgesia and spontaneous pain. Nonsteroidal anti-inflammatory drugs (NSAIDs are currently the first choice of drug to relieve TMD pain. NSAIDS were shown to exhibit anticonvulsant properties and suppress cortical neuron activities by enhancing neuronal voltage-gated potassium KCNQ/Kv7 channels (M-current, suggesting that specific activation of M-current might be beneficial for TMD pain. Results In this study, we selected a new anticonvulsant drug retigabine that specifically activates M-current, and investigated the effect of retigabine on inflammation of the temporomandibular joint (TMJ induced by complete Freund's adjuvant (CFA in rats. The results show that the head withdrawal threshold for escape from mechanical stimulation applied to facial skin over the TMJ in inflamed rats was significantly lower than that in control rats. Administration of centrally acting M-channel opener retigabine (2.5 and 7.5 mg/kg can dose-dependently raise the head withdrawal threshold of mechanical allodynia, and this analgesic effect can be reversed by the specific KCNQ channel blocker XE991 (3 mg/kg. Food intake is known to be negatively associated with TMJ inflammation. Food intake was increased significantly by the administration of retigabine (2.5 and 7.5 mg/kg, and this effect was reversed by XE991 (3 mg/kg. Furthermore, intracerebralventricular injection of retigabine further confirmed the analgesic effect of central retigabine on inflammatory TMJ. Conclusions Our findings indicate that central sensitization is involved in inflammatory TMJ pain and pharmacological intervention for controlling central hyperexcitability by activation of neuronal KCNQ/M-channels may have therapeutic potential for

  20. 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

  1. Spectroscopic Investigations, DFT Calculations, and Molecular Docking Studies of the Anticonvulsant (2E-2-[3-(1H-Imidazol-1-yl-1-phenylpropylidene]-N-(4-methylphenylhydrazinecarboxamide

    Directory of Open Access Journals (Sweden)

    Reem I. Al-Wabli

    2016-01-01

    Full Text Available Drug discovery for the management of neurological disorders is a challenging arena in medicinal chemistry. Vibrational spectral studies of (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-(4-methylphenylhydrazinecarboxamide ((2E-IPPMP have been recorded and analyzed to identify the functional groups and intermolecular/intramolecular interactions of the title molecule. The blue shift of the C-H stretching wavenumber reveals the presence of improper C-H⋯O hydrogen bonding. The equilibrium geometry, harmonic vibrational wavenumbers, Frontier orbital energy, and natural bond orbital analyses have been carried out using density functional theory with a B3LYP/6-311++G(d,p level of the basis set. The vibrational modes have been unambiguously assigned using potential energy distribution analysis. The scaled wavenumbers are in good agreement with the experimental results. Natural bond orbital analysis has confirmed the intermolecular/intramolecular charge transfer interactions. HOMO-LUMO analysis was carried out to explore charge delocalization on the (2E-IPPMP molecule. A molecular docking study has supported the anticonvulsant activity of the title molecule.

  2. 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

  3. 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; Arnold, Jonathon C

    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

  4. 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.

  5. Triazolines--XXVII. delta2-1,2,3-triazoline anticonvulsants: novel 'built-in' heterocyclic prodrugs with a unique 'dual-action' mechanism for impairing excitatory amino acid L-glutamate neurotransmission.

    Science.gov (United States)

    Kadaba, P K; Stevenson, P J; P-Nnane, I; Damani, L A

    1996-02-01

    The delta2-1,2,3-triazoline anticonvulsants (1) may be considered as representing a unique class of 'built-in' heterocyclic prodrugs where the active 'structure element' is an integral part of the ring system and can be identified only by a knowledge of their chemical reactivity and metabolism. Investigations on the metabolism and pharmacology of a lead triazoline, ADD17014 (1a), suggest that the triazolines function as 'prodrugs' and exert their anticonvulsant activity by impairing excitatory amino acid (EAA) L-glutamate (L-Glu) neurotransmission via a unique 'dual-action' mechanism. While an active beta-amino alcohol metabolite, 2a, from the parent prodrug acts as an N-methyl-D-aspartate (NMDA)/MK-801 receptor antagonist, the parent triazoline impairs the presynaptic release of L-Glu. Various pieces of theoretical reasoning and experimental evidence led to the elucidation of the dual-action mechanism. Based on the unique chemistry of the triazolines, the potential metabolic pathways and biotransformation products of 1a were predicted to be the beta-amino alcohols 2a and 2a', the alpha-amino acid 3a, the triazole 4a, the aziridine 5a, and the ketimine 6a. In vivo and in vitro pharmacological studies of 1a and potential metabolities, along with a full quantitative urinary metabolic profiling of 1a, indicated the beta-amino alcohol 2a as the active species. It was the only compound that inhibited the specific binding of [3H]MK-801 to the MK-801 site, 56% at 10 microM drug concentration, but itself had no anticonvulsant activity, suggesting 1a acted as a prodrug. Three metabolites were identified; 2a was the most predominant, with lesser amounts of 2a', and very minor amounts of aziridine 5a. Since only 5a can yield 2a', its formation indicated that the biotransformation of 1a occurred, at least in part, through 5a. No amino acid metabolite 3a was detected, which implied that no in vivo oxidation of 2a or oxidative biotransformation of 1a or 5a by hydroxylation at

  6. 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

  7. 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.

  8. Synthesis of 1-(4-methylsulfone-phenyl)-5-(4-fluoro-phenyl)-5-[14C]-1,2,3- triazole and 1-(4-sulfonamide-phenyl)-5-(4-fluoro-phenyl)-5-[14C]-1,2,3- triazole as novel carbon-14 anticonvulsant

    International Nuclear Information System (INIS)

    Two 1,2,3-triazole anticonvulsants, 1-(4-methylsulfone-phenyl)-5-(4-fluoro-phenyl)-5-[14C]-1,2,3-triazole and 1-(4-sulfonamide-phenyl)-5-(4- fluoro-phenyl)-5-[14C]-1,2,3-triazole, both labeled with carbon-14 in the 5-position were prepared from para-fluoro-benzonitrile-[cyano-14C]. (author)

  9. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and theoretical calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide: An anticonvulsant agent

    Science.gov (United States)

    Haress, Nadia G.; Govindarajan, Munusamy; AL-Wabli, Reem I.; Almutairi, Maha S.; Al-Alshaikh, Monirah A.; Al-Saadi, Abdulaziz A.; Attia, Mohamed I.

    2016-08-01

    Vibrational characteristics of the anticonvulsant agent, (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide ((2E)-IPHC) have been investigated. The computational data are obtained by adopting ab initio Hartree-Fock (HF) and DFT/B3LYP/6-31 + G(d,p) methods. The most stable conformer is identified by a potential energy scan. The optimized geometrical parameters indicated that the overall symmetry of the most stable conformer is CS. Atoms in molecules (AIM) analysis is contained out and the chemical bondings between the atoms are as characterized. Mulliken atomic charges and simulated thermo-molecular (heat capacity and enthalpy) characteristics of the (2E)-IPHC molecule also have been analyzed. The magnitude of the molecular electrostatic potential (MEP) of oxygen, hydrogen, and nitrogen atoms as well as phenyl and imidazole rings in the title molecule were investigated along with their contribution to the biological activity. The energy gap between HOMO and LUMO orbitals has been found to be 5.1334 eV in the gaseous phase. Excitation energies, oscillator strength and wavelengths were computed by the time-dependent density function theory (TD-DFT) approach. Predicted wavenumbers have been assigned and they are consistent with the experimental values. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the (2E)-IPHC molecule were computed by the gauge independent atomic orbital (GIAO) method and were compared with the experimental results.

  10. 2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure

    Energy Technology Data Exchange (ETDEWEB)

    Mangaiyarkarasi, G.; Kalaivani, D., E-mail: kalaivbalaj@yahoo.co.in [Affiliated to Bharathidasan University, Post Graduate and Research Department of Chemistry, Seethalakshmi Ramaswami College, Tiruchirappalli-620 002 (India)

    2013-12-15

    The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) (I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, {sup 1}H-NMR, {sup 13}C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. P-bar1. They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD{sub 50} values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes.

  11. 2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure

    Science.gov (United States)

    Mangaiyarkarasi, G.; Kalaivani, D.

    2013-12-01

    The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) ( I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate ( II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, 1H-NMR, 13C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. . They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD50 values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes.

  12. Experimental and Theoretical Studies of the Vibrational and Electronic Properties of (2E-2-[3-(1H-imidazol-1-yl-1-phenyl-propylidene]-N-phenylhydrazinecarboxamide: An Anticonvulsant Agent

    Directory of Open Access Journals (Sweden)

    Munusamy Govindarajan

    2015-10-01

    Full Text Available In the current investigation, the molecular structure of the anticonvulsant agent (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide ((2E-HIPC was theoretically modelled using ab initio Hartree-Fock (HF and density functional theory (DFT/B3LYP calculations. The Fourier transform (FT infrared and FT-Raman spectra of (2E-HIPC were also recorded, and the observed bands were assigned to the vibrational normal modes. The main functional groups were identified via vibrational analysis, and their absorption bands were assigned. A comparative analysis was performed for the computed and experimental results. Subtle differences were observed between the calculated and experimental UV-Vis spectra. Time-dependent density functional theory (TD-DFT excitation energies were calculated for five excited electronic states. The calculations were applied to simulate the spectra of (2E-HIPC, and these simulated spectra exhibited excellent agreement with the experimental spectra. The DFT/B3LYP/6-311++G(d,p method, after scaling, exhibited better agreement with the experimental values than the results obtained by the HF method. The energy, oscillator strength, and wavelength computed by TD-DFT (IEFPCM are consistent with the experimental results. The molecular electrostatic potential (MEP and frontier molecular orbitals (HOMO-LUMO were also determined to enable prediction of the structural changes and reactive sites. Mulliken population charges of the title molecule were also calculated in the gas phase. The NMR chemical shifts (13C and 1H were calculated using the gauge-including atomic orbital method and the B3LYP/6-311++G(d,p approach and were compared with the experimental values.

  13. Crystal structures of 2-methoxyisoindoline-1,3-dione, 1,3-dioxoisoindolin-2-yl methyl carbonate and 1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl methyl carbonate: three anticonvulsant compounds

    Directory of Open Access Journals (Sweden)

    Fortune Ezemobi

    2014-12-01

    Full Text Available The title compounds, C9H7NO3, (1, C10H7NO5, (2, and C14H9NO5, (3, are three potentially anticonvulsant compounds. Compounds (1 and (2 are isoindoline derivatives and (3 is an isoquinoline derivative. Compounds (2 and (3 crystallize with two independent molecules (A and B in their asymmetric units. In all three cases, the isoindoline and benzoisoquinoline moieties are planar [r.m.s. deviations are 0.021 Å for (1, 0.04 and 0.018 Å for (2, and 0.033 and 0.041 Å for (3]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3° for the N—O—Cmethyl group in (1, 71.01 (4 and 80.00 (4° for the N—O—C(=OO—Cmethyl groups in (2, and 75.62 (14 and 74.13 (4° for the same groups in (3. In the crystal of (1, there are unusual intermolecular C=O...C contacts of 2.794 (1 and 2.873 (1 Å present in molecules A and B, respectively. There are also C—H...O hydrogen bonds and π–π interactions [inter-centroid distance = 3.407 (3 Å] present, forming slabs lying parallel to (001. In the crystal of (2, the A and B molecules are linked by C—H...O hydrogen bonds, forming slabs parallel to (10-1, which are in turn linked via a number of π–π interactions [the most significant centroid–centroid distances are 3.4202 (7 and 3.5445 (7 Å], forming a three-dimensional structure. In the crystal of (3, the A and B molecules are linked via C—H...O hydrogen bonds, forming a three-dimensional structure, which is consolidated by π–π interactions [the most significant inter-centroid distances are 3.575 (3 and 3.578 (3 Å].

  14. 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

  15. Anticonvulsant Effect of Drosera burmannii Vahl

    OpenAIRE

    B. Hema; S Bhupendra; T. S. Mohamed Saleem; K. Gauthaman

    2009-01-01

    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 ...

  16. 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

  17. Anticonvulsant action of allopregnanolone in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Mikulecká, Anna; Haugvicová, Renata; Kasal, Alexander

    2006-01-01

    Roč. 70, č. 2-3 (2006), s. 110-117. ISSN 0920-1211 R&D Projects: GA AV ČR(CZ) IBS5011007 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40550506 Keywords : allopregnanolone * pentetrazol * rat Subject RIV: ED - Physiology Impact factor: 2.088, year: 2006

  18. Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships.

    Science.gov (United States)

    Altintaş, Handan; Ateş, Oznur; Uyde-Doğan, B Sönmez; Alp, F Ilkay; Kaleli, Deniz; Ozdemir, Osman; Birteksöz, Seher; Otük, Gülten; Atana, Dilek; Uzun, Meltem

    2006-01-01

    In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice. PMID:16618017

  19. 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.

  20. 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

  1. Synthesis and evaluation of phenytoin derivatives as anticonvulsant agents

    OpenAIRE

    DEODHAR, Meenakshi; SABLE, Pravin; Bhosale, Ashok; JUVALE, Kapil

    2009-01-01

    2,5-Dioxo-4,4-diphenylimidazolidine-1-carboxylic acid (2) was reacted with methyl ester of different amino acids (1a-c) and substituted benzhydrols (3a-b) in pyridine and in the presence of N,N dicyclohexyl carbodiimide (DCC) to yield a series of the title compounds, methyl 2-(2,5-dioxo-4,4-diphenylimidazolidine-1-carboxamido) substituted propanoate (4a-c) and benzhydryl 2,5-dioxo-4,4-diphenyl imidazolidine-1-carboxylate (5a-b). The structures of these compounds were established on th...

  2. Synthesis and anticonvulsant activity of substituted thiourea derivatives

    Directory of Open Access Journals (Sweden)

    Feyza Arıcıoğlu

    2011-05-01

    Full Text Available 4-Aminofenilasetik asitin sübstitüe izotiyosiyanatlar ile reaksiyonu sonucu, on iki adet yeni tiyoüre bileşiği sentezlenmiştir. Bileşiklerin kimyasal yapıları IR, 1H-NMR, kütle spektroskopisi ve elementel analiz testleri ile aydınlatılmıştır. Tüm bileşiklerin antikonvulsan aktiviteleri 50mg/kg dozda farelerde pentilentetrazol (PTZ ve maksimal elektroşok nöbet (MES testleri kullanılarak tayin edilmiştir. Bileşik 1b'nin (4-{[(4-klorofeniltiyokarbamoil]amino}fenil asetik asit, diğer bileşiklere oranla daha aktif olduğu saptanmıştır. Tüm seviyelerde konvulsiyon oranını düşüren 1b bileşiği aynı zamanda nöbet eşiğini de yükseltmiştir. Ayrıca nöbet başlangıç süresini 1.20 saniyeden 2.58 saniyeye, hayatta kalma oranını ise %50'den %95'e yükseltmiştir.

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

    OpenAIRE

    Sudhakara Rao Gerapati; Kalaichelvan V K; Ganguri Sudhakara Rao

    2015-01-01

    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 ...

  4. 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...

  5. Tissue distribution of newer anticonvulsant drugs in postmortem cases.

    Science.gov (United States)

    Levine, Barry; Phipps, Rebecca Jufer; Naso, Clare; Fahie, Kisha; Fowler, David

    2010-10-01

    Levetiracetam, hydroxycarbazepine (the primary product of oxcarbazepine use), and topiramate were quantified using the acid/neutral drug screening procedure employed by this laboratory. Briefly, blood or tissue homogenate spiked with an internal standard (cyclopentobarbital) was buffered to pH 5 and applied to Chem Elut® columns. The columns were washed with methylene chloride, collected, and evaporated to dryness. The residue was reconstituted with 0.033 M trimethylanilinium hydroxide and injected into a gas chromatograph equipped with a DB-5 analytical column (25 m × 0.32-mm i.d.) and a nitrogen-phosphorus detector. A calibration curve using four calibrators ranging in concentration from 2 to 20 mg/L was used for quantification. Despite the limited number of cases for each drug, there were some trends suggested by the data. None of the drugs displayed significant differences in concentration between the heart blood and peripheral (subclavian) blood specimens. Only the hydroxycarbazepine quantifications in one case (case 5) showed significant differences between the two blood sites. This is consistent with other acid/neutral drugs such as acetaminophen and meprobamate. It also appears that the liver and kidney concentrations of the three drugs are on the same order of magnitude as the blood concentrations. Only the levetiracetam concentration in one case (case 3) reflected a liver or kidney concentration greater than 5 times the blood concentration. PMID:21819796

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

    (B) receptor agonist baclofen, gabapentin was unable to inhibit transient lower esophageal sphincter relaxations in dogs. Because of high levels of GABA(B(1a)) in the canine nodose ganglion, this finding indirectly supports the inactivity of gabapentin on the GABA(B(1a,2)) heterodimer demonstrated in various...

  12. Anticonvulsant-like actions of baclofen in the rat hippocampal slice.

    OpenAIRE

    Ault, B.; Nadler, J V

    1983-01-01

    1 The effects of baclofen were tested on epileptiform discharge in the rat hippocampal slice. Slices were superfused with bicuculline methiodide (100 microM) and maximal periods of afterdischarge were evoked by stimulating the Schaffer collateral-commissural pathway in area CA1, mossy fibres in area CA3 or perforant path fibres in the fascia dentata or by antidromic stimulation of CA1 pyramidal cells. 2 (-)-Baclofen attenuated the afterdischarge evoked by stimulating all three sets of fibres ...

  13. Anticonvulsant action of GABA-B receptor agonist SKF97541 Differs from that of Baclofen

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2008-01-01

    Roč. 57, č. 5 (2008), s. 789-792. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/05/2581 Institutional research plan: CEZ:AV0Z50110509 Keywords : PTZ seizures * GABA -B * ontogeny Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

  14. 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

  15. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

    OpenAIRE

    Chouinard, Guy

    2006-01-01

    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, ...

  16. Anticonvulsant treatments of dysphoric mania: a trial of gabapentin, lamotrigine and carbamazepine in Iran

    OpenAIRE

    Young, Allan,

    2008-01-01

    Naghmeh Mokhber1, Carol J Lane2, Mohamad R Azarpazhooh3, Elham Salari4, Reza Fayazi5, Mohamad T Shakeri6, Allan H Young71Assistant Professor of Psychiatry, 3Assistant Professor of Neurology, 4Mashhad Department of Forensic Psychiatry, 5Assistant Professor of Psychiatry, 6Assistant Professor of Statistics, Mashhad University of Medical Science, Mashhad, Iran; 2Department of Psychiatry, University of British Columbia, Vancouver, Canada7Abstract: The treatment of dysphoric mania is challenging g...

  17. Drug-induced hypersensitivity syndrome due to anticonvulsants in a two-year-old boy.

    Science.gov (United States)

    Criado, Paulo Ricardo; Criado, Roberta F J; Vasconcellos, Cidia; Pegas, Jose Roberto P; Cera, Patrícia Calil

    2004-12-01

    Drug-induced hypersensitivity syndrome (DIHS) usually refers to severe cutaneous drug eruption associated with systemic involvement and potentially fatal outcome. We report a 2-year-old Caucasian boy who developed DIHS due to phenytoin and phenobarbital and who showed extensive internal organ involvement. We are alerting that failure to recognize this drug eruption and discontinue the culprit drug may result in increased severity, greater extent of internal organ involvement, and fatal outcome. The recent research about the influence of human herpesvirus 6 co-infection on the pathogenesis of DIHS is also discussed by the authors in this paper. PMID:15801266

  18. A Multi-System Approach Assessing the Interaction of Anticonvulsants with P-gp

    OpenAIRE

    Dickens, David; Yusof, Siti R.; Abbott, N. Joan; Weksler, Babette; Romero, Ignacio A; Couraud, Pierre-Olivier; Alfirevic, Ana; Pirmohamed, Munir; Owen, Andrew

    2013-01-01

    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 assa...

  19. Synthesis molecular modeling and anticonvulsant activity of some hydrazone, semicarbazone, and thiosemicarbazone derivatives of benzylidene camphor

    OpenAIRE

    Agrawal, Saurabh

    2014-01-01

    Saurabh Agrawal,1 Jainendra Jain,2 Ankit Kumar,3 Pratibha Gupta,4 Vikas Garg5 1Meerut Institute of Engineering and Technology, Meerut, Uttar Pradesh, India; 2Ram–Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India; 3Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India; 4Atarra Degree College, Atarra, Banda, India; 5Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnata...

  20. EXAMINATION OF THE ANTICONVULSANT PROPERTIES OF VOLTAGE-SENSITIVE CALCIUM CHANNEL INHIBITORS IN AMYGDALA KINDLED SEIZURES

    Science.gov (United States)

    Representatives from three different classes of voltage-sensitive calcium (VSC) channel inhibitors were assessed for their protection against amygdala kindled seizures. dult male long Evans rats (n=12) were implanted with electrodes in the amygdala and were stimulated once daily ...

  1. Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects

    Czech Academy of Sciences Publication Activity Database

    Suchomelová, Lucie; Baldwin, R. A.; Kubová, Hana; Thompson, K. W.; Sankar, R.; Wasterlain, C. G.

    2006-01-01

    Roč. 59, č. 2 (2006), s. 237-243. ISSN 0031-3998 Grant ostatní: ILAE(BE) Fellowship; Johnson&Johnson´s(US) Pharm. Res. Institute; NINDS(US) NS13515; NINDS(US) NS046516; NINDS(US) NS045911 Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * treatment * immature rats Subject RIV: ED - Physiology Impact factor: 2.619, year: 2006

  2. Anticonvulsant action of GABA(B) receptor positive modulator CGP7930 in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2012-01-01

    Roč. 100, 1-2 (2012), s. 49-54. ISSN 0920-1211 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GAP304/10/1274 Institutional research plan: CEZ:AV0Z50110509 Keywords : GABA(B) receptors * cerebral cortex * epileptic afterdischarges * immature rats Subject RIV: FH - Neurology Impact factor: 2.241, year: 2012

  3. Five percent CO2 is a potent, fast-acting inhalation anticonvulsant

    Czech Academy of Sciences Publication Activity Database

    Tolner, E. A.; Hochman, D. W.; Hassinen, P.; Otáhal, Jakub; Gaily, E.; Haglund, M. M.; Kubová, Hana; Schuchmann, S.; Vanhatalo, S.; Kaila, K.

    2011-01-01

    Roč. 52, č. 1 (2011), s. 104-114. ISSN 0013-9580 R&D Projects: GA AV ČR(CZ) 1QS501210509; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : pH * hypercarbia * epilepsy * human * electroencephalogram Subject RIV: FH - Neurology Impact factor: 3.961, year: 2011

  4. Metabotropic glutamate receptors as a target for anticonvulsant and anxiolytic action in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Mikulecká, Anna; Tichá, Kateřina; Lojková-Janečková, Denisa; Kubová, Hana

    2010-01-01

    Roč. 51, Suppl.3 (2010), s. 24-26. ISSN 0013-9580 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabotropic glutamate receptors * pharmacology * development Subject RIV: FH - Neurology Impact factor: 3.955, year: 2010

  5. Tumor promotion by an anticonvulsant agent, phenytoin, in mouse liver: correlation with CYP2B induction.

    Science.gov (United States)

    Diwan, B A; Henneman, J R; Nims, R W; Rice, J M

    1993-11-01

    To investigate the liver tumor promoting effects of phenytoin (5,5-diphenylhydantoin; DPH), 5 week old male D2B6F1 mice were given a single i.p. dose of 90 mg N-nitrosodiethylamine (NDEA)/kg body wt in tricaprylin. Control groups received tricaprylin alone. After 2 weeks, the mice were given a diet containing 500, 250 or 125 p.p.m. DPH. Ten mice from each treatment group were killed at 30 weeks of age, at which time 10/10 mice given 500 p.p.m. DPH after NDEA initiation had developed multiple hepatocellular foci and adenomas. Such lesions were found only in 2/10 mice given NDEA alone. By 60 weeks, when the experiment was concluded, the incidences (and multiplicities, in units of tumors per tumor-bearing mouse) of hepatocellular adenomas were 60% (1.8 +/- 0.8), 100% (11.6 +/- 5.5), 77% (4.4 +/- 3.3) or 71% (2.6 +/- 1.3) in mice exposed to NDEA alone, or NDEA followed by 500, 250 or 125 p.p.m. DPH respectively. Hepatocellular carcinomas (87% incidence) and hepatoblastomas (33% incidence) were found only in mice given 500 p.p.m. DPH following NDEA initiation. Dose-dependent and profound increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylase activity were detected in livers of B6C3F1 mice exposed for 14 days to dietary DPH (125, 250, 500 or 1000 p.p.m.). Similar increases in this activity were observed in D2B6F1 mice exposed to 500 and 250 p.p.m. for 30 or 60 weeks. Thus, increased hepatic CYP2B activity in mice exposed to DPH correlates with the tumor promoting effect of this compound. PMID:8242847

  6. Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

    International Nuclear Information System (INIS)

    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

  7. Anticonvulsant action of a new analogue of allopregnanolone in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Kubová, Hana; Kasal, Alexander

    2010-01-01

    Roč. 59, č. 2 (2010), s. 305-308. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA203/06/1605 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40550506 Keywords : neuroactive steroids * pentylenetetrazol * ontogeny Subject RIV: FH - Neurology Impact factor: 1.646, year: 2010

  8. An antagonist of calcium permeable AMPA receptors, IEM1460: Anticonvulsant action in immature rats?

    Czech Academy of Sciences Publication Activity Database

    Szczurowska, Ewa; Mareš, Pavel

    2015-01-01

    Roč. 109, Jan 2015 (2015), s. 106-113. ISSN 0920-1211 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : cortical epileptic afterdischarges * AMPA receptors * ontogeny * rat Subject RIV: FH - Neurology Impact factor: 2.015, year: 2014

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

    Directory of Open Access Journals (Sweden)

    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. Epilepsy therapy: anticonvulsants, lessons learned and unmet medical needs. Interview by Rona Williamson.

    Science.gov (United States)

    Klitgaard, Henrik

    2013-01-01

    Henrik Klitgaard, PhD, is currently Vice-President, UCB Fellow, Neurosciences Therapeutic Area and is based in Braine-l'Alleud, Belgium. He received a PhD in Human Physiology in 1989 at the August Krogh Institute at the University of Copenhagen (Denmark). During his university career, Klitgaard worked at the Pasteur Institute in Paris (France) and at Harvard University (MA, USA). Klitgaard is a leading figure in the epilepsy research community, thanks to more than 80 peer-reviewed papers and 15 reviews and book chapters, as well as frequent lectures at top neuroscience and epilepsy science meetings. His memberships and accolades include a position on the US National Institute of Health's epilepsy advisory committee, membership of the Neurobiology Committees of both the International League Against Epilepsy and American Epilepsy Society and a seat on the Scientific Advisory Committee of the patient organization C.U.R.E. (Citizens United for Research in Epilepsy). For more than two decades, Klitgaard has conducted antiepileptic drug discovery in the pharmaceutical industry. He has contributed numerous publications on basic and applied aspects of epilepsy research and has frequently been an invited speaker at epilepsy congresses and meetings. During his career in the pharmaceutical industry, Klitgaard has been involved in the discovery and development of antiepileptic drugs at both Novo Nordisk A/S and UCB Pharma. He is also currently involved in the development of two clinical and several preclinical AED candidates. PMID:23253386

  11. Aminoalkylpyridines (AAPs), triazoline metabolite analogues, as anticonvulsants highly effective in the MES test.

    Science.gov (United States)

    Kadaba, Pankaja K; Dixit, Trupti

    2003-10-01

    Elucidation of the metabolism and pharmacology of 1,2,3-triazolines (TRs) led to the identification of the triazoline pharmacophore and the evolution of the aminoalkylpyridines (AAPs). The AAPs have no activity in the scMet test but are highly effective in the MES seizure test by the oral route. The AAPs bind to the sigma(1) receptor with low affinity, but high selectivity. They impair Glu release to the same extent as the triazolines and afforded a high degree of protection in the kindled rat. They show no affinity for the NMDA/PCP receptor sites; thus the toxic side effects of NMDA antagonists are absent in the sigma selective AAPs. Variations of the heterocyclic unit, the alkyl chain and the amino group in the AAP leads, indicated that the 4-pyridyl substituent along with a methyl (alkyl) group, and a 4-C1, 3-C1 or 3,4-C1(2) substitution on the N-phenyl group, afforded the most active compounds. Amino group modification by acylation did not improve activity. The hydrazone compounds were the most active. Although the AAPs are very effective in the MES and the kindling models of epilepsy, they showed only low to moderate activity in protecting neuronal cells in stroke-induced cerebral ischemia. In the case of the TR compounds, even the least effective TR afforded 47% protection from neuronal injury. It is not known at this point, whether activity in both the MES and scMet tests, which would imply a role for both Glu and GABA, is a prerequisite for antiischemic activity. PMID:12871088

  12. Solvent effects on the structure-property relationship of anticonvulsant hydantoin derivatives: A solvatochromic analysis

    Directory of Open Access Journals (Sweden)

    Trišović Nemanja

    2011-10-01

    Full Text Available Abstract Considering the pharmaceutical importance of hydantoins, a set of 25 derivatives of phenytoin, nirvanol and 5-methyl-5-phenylhydantoin, the lipophilicities of which were gradually increased by the introduction of different alkyl, cycloalkyl and alkenyl groups in position N3, was synthesized. Their properties under consideration were either estimated empirically, by UV/Vis spectroscopy, or calculated using established medicinal chemistry software. The UV absorption spectra of the investigated compounds were recorded in the region from 200 to 400 nm, in selected solvents of different polarities. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER concept proposed by Kamlet and Taft. Furthermore, the relationships between solvent-solute interactions and selected structural features of the solutes, which are believed to markedly affect the processes of absorption, distribution, metabolism, excretion and toxicity (ADMETox, were discussed. Satisfactory correlations were found between hydrogen bonding properties and solute size and the in silico calculated bioactivity descriptors, in particular %Abs. (human intestinal absorption, log BB (blood-brain barrier permeation and log kA (protein binding affinities parameters. In view of the results of this study, the investigated hydantoin derivatives met the pharmacokinetic criteria for pre-selection as drug candidates and qualified them for the pharmacodynamic phase of antiepileptic drug development.

  13. Anticonvulsant and behavioral effects of GABA(B) receptor positive modulator CGP7930 in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Tichá, Kateřina; Mikulecká, Anna

    2013-01-01

    Roč. 28, č. 1 (2013), s. 113-120. ISSN 1525-5050 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GAP304/10/1274 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : GABAB receptor * pharmacology * ontogeny * rat Subject RIV: FH - Neurology Impact factor: 2.061, year: 2013

  14. Age-dependent anticonvulsant action of antagonists of group I glutamate metabotropic receptors in rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2009-01-01

    Roč. 83, 2-3 (2009), s. 215-223. ISSN 0920-1211 R&D Projects: GA ČR(CZ) GA305/06/1188 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabotropic glutamate receptors * anticonvulsan effect * ontogeny Subject RIV: FH - Neurology Impact factor: 2.479, year: 2009

  15. 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

  16. Identification of both GABAA receptors and voltage-activated Na+ channels as molecular targets of anticonvulsant α-asarone

    Directory of Open Access Journals (Sweden)

    Ze-JunWang

    2014-03-01

    Full Text Available Alpha (α-asarone, a major effective component isolated from the Chinese medicinal herb Acorus tatarinowii, is clinically used as medication for treating epilepsy, cough, bronchitis, and asthma. In the present study, we demonstrated that α-asarone targets central nervous system GABAA receptor as well as voltage-gated Na+ channels. Using whole-cell patch-clamp recording, -asarone inhibited spontaneous firing of output neurons, mitral cells (MCs, in mouse olfactory bulb brain slice preparations and hyperpolarized the membrane potential of MCs. The inhibitory effect of α-asarone persisted in the presence of ionotropic glutamate receptor blockers but was eliminated after adding a GABAA receptor blocker, suggesting that GABAA receptors mediated the inhibition of MCs by α-asarone. This hypothesis was supported by the finding that α-asarone evoked an outward current, but did not influence inhibitory postsynaptic currents (IPSCs. In addition to inhibiting spontaneous firing, α-asarone also inhibited the Nav1.2 channel, a dominant rat brain Na+ channel subtype. The effects of α-asarone on a defined Nav1.2 were characterized using transfected cells that stably expressed the Nav1.2 channel isoform. α-Asarone displayed strong tonic inhibition of Nav1.2 currents in a concentration- and membrane potential-dependent fashion. α-Asarone reduced channel availability in steady-state inactivation protocols by enhancing or stabilizing Na+ channel inactivation. Both Na+ channel blockade and activation of GABAA receptors provide a possible mechanism for the known anti-epileptic effects of α-asarone. It also suggests that α-asarone could benefit patients with cough possibly through inhibiting a Na+ channel subtype to inhibit peripheral and/or central sensitization of cough reflexes.

  17. Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.

    OpenAIRE

    Turski, L.; Meldrum, B. S.; E.A. Cavalheiro; Calderazzo-Filho, L S; Bortolotto, Z A; Ikonomidou-Turski, C; Turski, W. A.

    1987-01-01

    We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizur...

  18. Evaluation of anticonvulsant activity of ACE inhibitors (imidapril and quinapril in experimentally induced animal models of epilepsy

    Directory of Open Access Journals (Sweden)

    Pushpa VH

    2016-06-01

    Conclusions: Quinapril and imidapril in a dose dependent manner showed increase in antiepileptic activity, imidapril has better antiepileptic activity when compared to quinapril. [Int J Basic Clin Pharmacol 2016; 5(3.000: 798-801

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

    OpenAIRE

    Ricardo Alberto Moreno; Doris Hupfeld Moreno; Márcia Britto de Macedo Soares; Roberto Ratzke

    2004-01-01

    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 ac...

  20. Anticonvulsant and neuroprotective effect of (S)-3,4-dicarboxyphenylglycine against seizures induced in immature rats by homocysteic acid

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Druga, Rastislav; Haugvicová, Renata; Mareš, Pavel; Otáhal, Jakub

    2008-01-01

    Roč. 54, č. 4 (2008), s. 665-675. ISSN 0028-3908 R&D Projects: GA ČR GA309/02/1238; GA ČR(CZ) GA309/05/2015 Institutional research plan: CEZ:AV0Z50110509 Keywords : DL-homocysteic acid induced seizures * mGluR8 agonist (S)-3,4-DCPG * protection Subject RIV: FH - Neurology Impact factor: 3.383, year: 2008

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

    OpenAIRE

    Gao, Fei

    2014-01-01

    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&rsq...

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

    OpenAIRE

    Luszczki Jarogniew J.; Marzeda Ewa; Kondrat-Wrobel Maria W.; Pyrka Daniel; Kocharov Sergey L.; Florek-Luszczki Magdalena

    2014-01-01

    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 ...

  3. [The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

    Science.gov (United States)

    Belkina, L M; Korchazhkina, N B; Kamskova, Iu G; Fomin, N A

    1997-01-01

    The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta. The cardioprotective effect of the drug was shown due to its positive chronotropic action rather than its inotropic one. Thus, SV may be used as an effective drug for the prevention and treatment of postinfarct cardiac dysfunctions. PMID:9235532

  4. Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method

    OpenAIRE

    Elsas, S.-M.; Rossi, D J; Raber, J.; White, G.; Seeley, C.-A.; Gregory, W. L.; Mohr, C.; Pfankuch, T.; Soumyanath, A.

    2010-01-01

    Potential mechanisms of Passiflora incarnata extracts and the effect of extraction methods on ingredients and biological effects were explored. Using the same batch of plant material, total flavonoid yields as measured by high performance liquid chromatography coupled to diode array detection (HPLC-DAD) increased substantially with hot vs. cold extraction methods.

  5. Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHT-untreated epileptic patients. I. Sister chromatid exchange (SCE) analysis.

    Science.gov (United States)

    Kaul, A; Goyle, S

    1999-01-01

    Phenytoin (PHT) is a widely prescribed antiepileptic drug. Its potential to interact with genetic material was investigated in a set of 30 epileptic patients (age 10-30 years) prior to and following the administration of PHT over a period of 9 months (grouped in a multiple of 3 months) and 40 control subjects in relation to age, sex, duration of drug therapy, and plasma concentration of PHT, using the sister chromatid exchange (SCE) frequency assay. Plasma levels of the phenytoin were measured by biochemical assay in epileptic patients before and after the PHT therapy. The peripheral blood lymphocytes were cultured and harvested at 72 h. The frequency of SCE was significantly higher (P genotoxic effect as expressed by the induction of increased SCE rates in treated epileptics, while disease does not play any role in inducing genetic damage as shown by no difference in SCE frequencies between control subjects and PHT-untreated epileptic patients. PMID:10321411

  6. 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

    OpenAIRE

    Melania Maria Ramos de Amorim; Luiz Carlos Santos; Ana Maria Feitosa Porto; Leila Katz Dias Martins; Valdson Vieira

    2000-01-01

    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 aco...

  7. Hepatic enzymes' level during chronic use of anticonvulsant drugs Dosagens de enzimas hepáticas em pacientes em uso crônico de drogas antiepiléticas

    Directory of Open Access Journals (Sweden)

    Mauricio Hoshino

    1995-12-01

    Full Text Available We studied retrospectively 894 adult epileptic patients treated during the period from 1983 to 1992. Hepatic enzymes abnormal values were seen in 49%(n=438. In 22.3%(n=200, at least 2 enzyme levels in different moments were altered. They were divided in three groups: GI with alterations at transaminases (3%, n=6, GII with alterations at GGT and AP enzymes (72%,n=144 and GIII with alterations in both groups (25%, n=50. No patient developed clinical symptoms of liver disease. The increase of gamma-glutamil-transferase (GGT and alkaline phosphatase (AP levels is frequent and not necessarily pathological. Slight increase of transaminases can occur with no clinical correlation. The routine screening of hepatic enzymes level during the chronic use of anticonvulsivant drugs in adults has a questionable value.Oitocentos e noventa e quatro pacientes epiléticos adultos tratados no período de 1983 a 1992 foram estudados retrospectivamente. Valores anormais de enzimas hepáticas foram detectados em 49% (n=438 dos casos. Em 200 pacientes (22,3%, ao menos duas dosagens obtidas em momentos diferentes estavam alteradas. Estes últimos foram divididos em 3 grupos: GI, com alterações de transaminases (3%, n=6; GII com alterações de gama-glutamil-transferase (GGT e fosfatase alcalina (AP (72%, n=144 e GIII com alterações nos dois grupos de enzimas (25%, n=50. Nenhum paciente desenvolveu sinais ou sintomas de doença hepática. O aumento de GGT e AP em pacientes em uso de drogas antiepiléticas é frequente e pode não ter significado patológico. Pequenos aumentos de transaminases também podem ocorrer sem correlação clínica.

  8. Spectroscopic Investigations, DFT Calculations, and Molecular Docking Studies of the Anticonvulsant (2E)-2-[3-(1H-Imidazol-1-yl)-1-phenylpropylidene]-N-(4-methylphenyl)hydrazinecarboxamide

    OpenAIRE

    Reem I. Al-Wabli; Manimaran, Devarasu; John, Liji; Joe, Isaac Hubert; Haress, Nadia G.; Attia, Mohamed I.

    2016-01-01

    Drug discovery for the management of neurological disorders is a challenging arena in medicinal chemistry. Vibrational spectral studies of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]-N-(4-methylphenyl)hydrazinecarboxamide ((2E)-IPPMP) have been recorded and analyzed to identify the functional groups and intermolecular/intramolecular interactions of the title molecule. The blue shift of the C-H stretching wavenumber reveals the presence of improper C-H⋯O hydrogen bonding. The equilibrium...

  9. 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

    OpenAIRE

    Jazmín Arteaga-Vázquez; Leonora Luna-Muñoz; Mutchinick, Osvaldo M.

    2012-01-01

    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 (RY...

  10. 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; Krogsgaard-Larsen, Povl; Schousboe, Arne; White, H Steve

    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...

  11. 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.

  12. Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish)

    OpenAIRE

    Torres-Hernández, Bianca A.; Del Valle-Mojica, Lisa M.; Ortíz, José G.

    2015-01-01

    Background Anticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs. Methods All drug treatments we...

  13. Role of Various Vitamins in the Patients with Epilepsy

    Directory of Open Access Journals (Sweden)

    Mohammad Asif

    2013-04-01

    Full Text Available In this review, we study the effect of various vitamins in the epileptic patients. These vitamins are generally may reduce seizure frequency and treating adverse effect of anticonvulsant drugs. Supplementation with folic acid, vitamin B6, vitamin E, biotin, vitamin D, may be needed to prevent or treat deficiencies resulting from the use of anticonvulsant drugs. Thiamine may improve cognitive function in the epileptic patients. Vitamin K1 has been recommended near the end of pregnancy for women taking anticonvulsant drugs. Vitamins therapy is not a substitute for anticonvulsant medications.

  14. Angelman syndrome

    Science.gov (United States)

    ... condition. Anticonvulsant medicines help control seizures Behavior therapy helps manage hyperactivity, sleep problems, and development problems Occupational and speech therapy manage speech problems and teach living skills Physical ...

  15. Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorder

    NARCIS (Netherlands)

    Post, RM; Altshuler, LL; Frye, MA; Suppes, T; McElroy, SL; Keck, PE; Leverich, GS; Kupka, R; Nolen, WA; Luckenbaugh, DA; Walden, J; Grunze, H

    2005-01-01

    Objective: Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar disord

  16. Phenytoin Induced Osteopathy -Too Common to be Neglected

    OpenAIRE

    Patil, Milind Machhindra; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar; Pillai, Vivekanandan

    2015-01-01

    Anticonvulsants have the broad spectrum of side effects on the bone that are collectively known as osteopathy. Anticonvulsant induced osteopathy can have detrimental consequences. We present an unusual case that uniquely highlights both adverse effects of phenytoin on bone metabolism and side effects of its overtreatment.

  17. Toxic epidermal necrolysis in a patient receiving concurrent phenytoin and whole brain and thoracic radiotherapy

    Science.gov (United States)

    Ahmed, Imtiaz; Biswas, Ahitagni; Krishnamurthy, Sapna; Julka, Pramod K.

    2014-01-01

    Toxic epidermal necrolysis (TEN) is a severe drug induced type IV hypersensitivity syndrome that can be caused by anticonvulsant drugs, especially the aromatic anticonvulsants such as phenytoin. Most patients with brain metastasis receive whole brain radiotherapy along with anti-edema measures and anticonvulsants either as prophylactic or for symptom control; phenytoin being the most commonly used drug. In a subset of patients, cranial irradiation may act as a precipitating factor along with anticonvulsants for the development of TEN. We report a 54-year-old patient with metastatic non-small cell lung cancer treated with palliative whole brain and mediastinal radiotherapy with concurrent phenytoin-developing TEN, which started within the radiation portals with subsequent generalization. Though a rare, but serious complication, avoidance of the use of phenytoin concurrent with radiotherapy, replacing phenytoin with newer anticonvulsants, early recognition, aggressive management and awareness of this possible complication has been implied upon in this report. PMID:25399219

  18. 半夏与钩藤生物总碱联合抗惊厥作用及毒性反应的定量评价%Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice

    Institute of Scientific and Technical Information of China (English)

    张密; 李禄金; 吕映华; 郑青山

    2010-01-01

    目的:利用已发表的半夏生物总碱(pinellia total alkaloid,PTA)与钩藤生物总碱(uncaria total alkaloid,UTA)联合抗惊厥和毒性作用数据,全面定量评价其相互作用和组方合理性.方法:采用等效图法(isobologram)和计算机模拟技术,定量评价不同强度(0%~99%)有效剂量(ED)和致死剂量(LD)的相互作用,并综合计算其获益指数(BI)和治疗指数(TI).结果:3个配比(PTA:UTA=1:4,1:1,4:1)有协同作用趋势.由于最高剂量的有效率均低于70%,给参数计算和研究结论带来不确定性.PTA和UTA按4:1联用的毒性呈现拮抗作用,其它2个配比毒性拮抗作用不明确.基于ED和LD参数的综合分析,3个配比的BI均大于1,其中4:1配比的减毒增效作用明确,TI增大.结论:PTA和UTA按4:1给药后安全性和有效性提高,呈现配伍优势.从方法学角度,本研究可对同类实验的设计和分析提供参考.

  19. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... epilepsy to discuss these medication issues with her health care providers. Additionally, some anticonvulsant medications can interact with ... hormones, seizures, and medications. Issues of Importance for Health Care Providers An important point for adults with TSC ...

  20. 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

  1. [The pharmacological differences between kynurenine- and korazol-induced seizures (the participation of GABA-B receptors and dopamine)].

    Science.gov (United States)

    Lapin, I P

    1998-01-01

    In experiments of male SHR (nonbred) and C57B1/6 mice [correction of rats] bicucullin intensified corasole-induced convulsions but had no effect on kynurenine convulsions, removed the anticonvulsive effect of phenibut against kynurenine and did not affect the anticonvulsive effect of diazepam against corasole. Phenibut and baclofen reduced the anticonvulsive effect of diazepam against corasole and caffeine. Haloperidol increased kynurenine-induced convulsions and had no effect on those caused by corasole. Dopamine removed the effect of haloperidol. Haloperidol and 6-oxydopamine weakened the sedative effect of phenibut. Blockade of GAMAB-receptors and weakening of dopaminergic activity are important in the mechanisms of kynurenine convulsions, and blockage of GABAA-receptors unrelated to it is important in the mechanisms of corasole convulsions. A functional antagonism in anticonvulsive activity may exist between these receptors. Bicucullin may probably have an effect both on GABAA- and GABAB-receptors. PMID:9621167

  2. Interleukin-6-type cytokines in neuroprotection and neuromodulation: Oncostatin M, but not leukemia inhibitory factor, requires neuronal Adenosine A1 receptor function

    NARCIS (Netherlands)

    Moidunny, S.; Dias, R.; Van Calker, D.; Boddeke, H.; Sebastiao, A.; Biber, K.

    2010-01-01

    Objective: Adenosine is a neuromodulator in the central nervous system exhibiting anticonvulsive, neuroprotective and sedating/sleep regulating properties. A pathophysiological importance of adenosine in various neuropsychiatric diseases (e.g. epilepsy, neurodegenerative disorders, apoplexia and moo

  3. [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.

  4. Lamotrigine

    Science.gov (United States)

    ... effective when people experience the actual episodes of depression or mania, so other medications must be used to help people recover from these episodes. Lamotrigine is in a class of medications called anticonvulsants. It works by decreasing ...

  5. Carbamazepine

    Science.gov (United States)

    ... depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing ...

  6. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... everolimus) was approved by the Food and Drug Administration (FDA) in October 2010 for treatment of TSC- ... epilepsy to discuss these medication issues with her health care providers. Additionally, some anticonvulsant medications can interact ...

  7. 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.

  8. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... which the liver metabolizes estrogen. The dosage for emergency contraception (morning after pill) will also depend on the type of anticonvulsant medication a woman takes. The use of barrier methods such as a diaphragm, sponges, ...

  9. Painful Diabetic Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment and Management

    DEFF Research Database (Denmark)

    Tesfaye, S; Vileikyte, L; Rayman, G;

    2011-01-01

    , taking into consideration co-morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include the tricyclic antidepressants (TCA), the selective serotonin and noradrenaline reuptake inhibitors (SNRIs), anticonvulsants, opiates, membrane stabilizers, the antioxidant alpha...

  10. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... 525-4526). If you are transitioning from a pediatric neurologist to an adult neurologist then ask that ... epilepsy to discuss these medication issues with her health care providers. Additionally, some anticonvulsant medications can interact ...

  11. Appearing and disappearing CT scan abnormalities and seizures.

    OpenAIRE

    P K Sethi; Kumar, B.R.; Madan, V S; Mohan, V

    1985-01-01

    A group of patients presenting with seizures (focal or generalised) and abnormal CT scans who, on follow up, showed complete resolution of the CT scan changes, without any treatment other than anticonvulsants, are described.

  12. Could antagonists of excitatory amino acid receptors be used as antiepileptics in pediatric epileptology?

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2006. s. 76-76. [Eilat conference on new antiepileptic drugs /8./. 10.09.2006-14.09.2006, Sitges] Institutional research plan: CEZ:AV0Z50110509 Keywords : anticonvulsive effect * antagonists * glutamate receptors Subject RIV: ED - Physiology

  13. Metabotropní glutamátové receptory jako možný cíl antiepileptické terapie

    Czech Academy of Sciences Publication Activity Database

    Lojková, Denisa; Mareš, Pavel

    2007-01-01

    Roč. 56, č. 2 (2007), s. 60-68. ISSN 0009-0557 Institutional research plan: CEZ:AV0Z50110509 Keywords : experimental model * anticonvulsant action * metabotropic glutamate receptors Subject RIV: ED - Physiology

  14. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... epilepsy to discuss these medication issues with her health care providers. Additionally, some anticonvulsant medications can interact ... hormones, seizures, and medications. Issues of Importance for Health Care Providers An important point for adults with ...

  15. Restless Legs Syndrome

    Science.gov (United States)

    ... sitting, and toss and turn in bed. A classic feature of RLS is that the symptoms are ... exacerbation of sleep apnea, and the risk of addiction. Anticonvulsants such as gabapentin and pregabalin can decrease ...

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Treatment of Generalized Anxiety Disorder: A Comprehensive Review of the Literature for Psychopharmacologic Alternatives to Newer Antidepressants and Benzodiazepines

    OpenAIRE

    Huh, John; Goebert, Deborah; Takeshita, Junji; Lu, Brett Y.; Kang, Mark

    2011-01-01

    Objective: Generalized anxiety disorder (GAD) is common, chronic, and debilitating. Treatment with benzodiazepines and newer antidepressants is often inadequate. This article reviews the effectiveness of alternative and augmenting medications, such as older antidepressants, antipsychotics, anticonvulsants, and β-blockers.

  1. Central mechanisms of cranial nerve stimulation for epilepsy

    OpenAIRE

    Fanselow, Erika E

    2012-01-01

    Stimulation of peripheral cranial nerves has been shown to exert anticonvulsant effects in animal models as well as in human patients. Specifically, stimulation of both the trigeminal and vagus nerves has been shown in multiple clinical trials to be anticonvulsant, and stimulation of these nerves at therapeutic levels does not cause pain or negatively affect brain function. However, the neuronal mechanisms by which such stimulation exerts therapeutic effects are not well understood. In this r...

  2. Study of efficacy of the combination of carbamazepine with nootropics on cognitive processes in epilepsy

    OpenAIRE

    Ivanov A.V.; Opryshko V.I.

    2013-01-01

    The authors studied the efficacy of combination of carbamazepine with nootropic drugs on cognitive processes in patients with epilepsy in experiment in order to reduce the side effects of anticonvulsant therapy. Analysis of anticonvulsant effect of the combination of drugs was carried out on 36 white nonlinear rats of both sexes weighing 160-180 g by the method of maximum electroshock, and the analysis of antiamnestic effect - using a model of retrograde amnesia on 80 white adult male rats we...

  3. Cerebroprotective prevention of memory disorders using sodium valproate

    OpenAIRE

    Ivanov, A. V.

    2013-01-01

    Epilepsy is the disease resulting in impaired cognitive function. The paper deals with the use of nootropics against the background of an anticonvulsant effect. Results of experiments on rats showed that investigated nootropics piracetam (500 mg/kg), citicoline (500 mg/kg), memantine (10 mg/kg) in combination with sodium valproate (80 mg/kg) improve memory and do not change its anticonvulsant effect.

  4. Prevalence of Treated Epilepsy in Korea Based on National Health Insurance Data

    OpenAIRE

    Lee, Seo-Young; Jung, Ki-Young; Lee, Il Keun; Yi, Sang Do; Cho, Yong Won; Kim, Dong Wook; Hwang, Seung-Sik; Kim, Sejin; ,

    2012-01-01

    The Korean national health security system covers the entire population and all medical facilities. We aimed to estimate epilepsy prevalence, anticonvulsant utilization pattern and the cost. We identified prevalent epilepsy patients by the prescription of anticonvulsants under the diagnostic codes suggesting seizure or epilepsy from 2007 Korean National Health Insurance databases. The information of demography, residential area, the kind of medical security service reflecting economic status,...

  5. Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

    OpenAIRE

    Russell, Jason L.; Spiller, Henry A.; Baker, Daniel D.

    2015-01-01

    Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potent...

  6. 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.

  7. Anti epileptic activity of ocimum species: A brief review

    Directory of Open Access Journals (Sweden)

    Chhaya Agarwal, N. L. Sharma, S. S. Gaurav

    2013-12-01

    Full Text Available The Ocimum species is a medicinal herb used in the indigenous system of medicine. Ocimum sp. have variety of biological, pharmacological properties such as antibacterial, antiviral, antifungal, antimalarial, anthelmentic, antidiarrhoeal, antiinflammatory, antihypertensive, cardioprotective, central nervous system (CNS depressant, antidiabetic, antithyroidic, antioxidant, anticancer, chemopreventive, radioprotective, immunomodulatory, antifertility, antiulcer, antiarthritic, antistress, antileucodermal and anticoagulant activities. Sevral species of Ocimum are used to cure central nervous system (CNS disorders.in various part of the world due to its anticonvulsant property .epilepsy is a chronic disorder which is characterized by seizures. Seizures are resistant to treatment with currently available anticonvulsant drug (AEDs in about one out of three patient with epilepsy. This review refers to the study of ocimum as an antiepileptic drug (AEDs because of its specific anticonvulsant property.

  8. Lithium and renal and upper urinary tract tumors

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVES: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions for...... lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals. METHODS: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all......) benign. Analyses were adjusted for the number of prescriptions for lithium/anticonvulsants, antipsychotic agents, antidepressants, and use of all other types of medication; age; gender; employment status; calendar year; and a diagnosis of bipolar disorder. RESULTS: Continued treatment with lithium was...

  9. Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats.

    Science.gov (United States)

    Frankel, Sari; Medvedeva, Natalia; Gutherz, Samuel; Kulick, Catherine; Kondratyev, Alexei; Forcelli, Patrick A

    2016-04-01

    Anticonvulsant drugs, when given during vulnerable periods of brain development, can have long-lasting consequences on nervous system function. In rats, the second postnatal week approximately corresponds to the late third trimester of gestation/early infancy in humans. Exposure to phenobarbital during this period has been associated with deficits in learning and memory, anxiety-like behavior, and social behavior, among other domains. Phenobarbital is the most common anticonvulsant drug used in neonatology. Several other drugs, such as lamotrigine, phenytoin, and clonazepam, have also been reported to trigger behavioral changes. A new generation anticonvulsant drug, retigabine, has not previously been evaluated for long-term effects on behavior. Retigabine acts as an activator of KCNQ channels, a mechanism that is unique among anticonvulsants. Here, we examined the effects retigabine exposure from postnatal day (P)7 to P14 on behavior in adult rats. We compared these effects with those produced by phenobarbital (as a positive control) and saline (as a negative control). Motor behavior was assessed by using the open field and rotarod, anxiety-like behavior by the open field, elevated plus maze, and light-dark transition task, and learning/memory by the passive avoidance task; social interactions were assessed in same-treatment pairs, and nociceptive sensitivity was assessed via the tail-flick assay. Motor behavior was unaltered by exposure to either drug. We found that retigabine exposure and phenobarbital exposure both induced increased anxiety-like behavior in adult animals. Phenobarbital, but not retigabine, exposure impaired learning and memory. These drugs also differed in their effects on social behavior, with retigabine-exposed animals displaying greater social interaction than phenobarbital-exposed animals. These results indicate that neonatal retigabine induces a subset of behavioral alterations previously described for other anticonvulsant drugs and extend

  10. 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.

  11. 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.

  12. 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

  13. Secondary hypogammaglobilinemia after use of carbamazepine: case report and review

    Directory of Open Access Journals (Sweden)

    Castro Ana Paula B Moschione

    2001-01-01

    Full Text Available Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

  14. Prevention of strychnine-induced seizures and death by the N-methylated glycine derivatives betaine, dimethylglycine and sarcosine.

    Science.gov (United States)

    Freed, W J

    1985-04-01

    Betaine (N,N,N-trimethylglycine) and N,N-dimethylglycine have been reported to have anticonvulsant properties in animals. The purpose of the present study was to determine whether these compounds can antagonize strychnine-induced seizures when administered intraperitoneally and to compare their effects with those of sarcosine (N-methylglycine) and glycine. Betaine, N,N-dimethylglycine and sarcosine were equipotent in decreasing the incidence of seizures and death, causing a 38 to 72 percent decrease in the incidence of seizures and death at a dosage of 5 mmole/kg. Glycine had no effect. Thus anticonvulsant activity is conferred to glycine by a single N-methylation. PMID:2581277

  15. A Case of Vascular Hemichorea Responding to Topiramate

    Directory of Open Access Journals (Sweden)

    Jee-Ae Kim

    2009-10-01

    Full Text Available Although vascular chorea often comes into remission spontaneously, a few patients may remain with persistent movement disorder. Most movements respond well to neuroleptics as well as other antidopaminergic drugs, but some patients show poor responses to those neuroleptics. Topiramate is a widely used of broad-spectrum anticonvulsant possessing a complex mechanism of action. It has been proven to enhance gamma-aminobutyrate acid activity and to be effective in the control of other movement disorders. We describe a 63-year-old woman with intractable vascular hemichorea which was controlled with anti-convulsant, topiramate.

  16. Toxic epidermal necrolysis associated with radiotherapy and phenytoin in a patient with non-Hodking's lymphoma: A case report.

    Science.gov (United States)

    Keklik, Fatma; Özkan, Melda Cömert; Yenipazar, Gizem Kocabaş; Yaman, Banu; Saydam, Güray; Şahin, Fahri

    2016-01-01

    Toxic epidermal necrolysis (TEN) is a disease which is characterized by fever and desquamation of the skin and mucosal membranes. It is usually related with drugs, especially aromatic anticonvulsants which are recognized as the most common cause of this disorder. Cranial irradiation may act as a precipitating factor along with anticonvulsants for the development of TEN. We report a 28-year-old patient with central nervous system (CNS) relapsed non-Hodgkin lymphoma (NHL) who developed TEN after cranial radiotherapy and concurrent phenytoin treatment. PMID:26900363

  17. Functionalized formazans: A review on recent progress in their pharmacological activities

    Directory of Open Access Journals (Sweden)

    Ahmad S. Shawali

    2015-05-01

    Full Text Available This review provides an up to date information about the diverse pharmaceutical activities of formazans. The bibliography includes 97 references which have been published during the period from 1980 to 2013. The covered biological activities of the title compounds include antioxidant, anticonvulsant, therapeutic, anthelmintic, anti-tubercular, antiviral, anti-inflammatory, anticancer, anti-HIV, antimicrobial, antiparkinsonian, cardiovascular and antiproliferative activities.

  18. Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice.

    OpenAIRE

    Puatanachokchai, Rawiwan; Kakuni, Masakazu; Wanibuchi, Hideki; KINOSHITA, ANNA; Kang, Jin Seok; Salim, Elsayed I.; Morimura, Keiichirou; Tamano, Seiko; Merlino, Glenn T.; FUKUSHIMA, SHOJI

    2009-01-01

    KEYWORDS-CLASSIFICATION: administration & dosage;Animals;Anticonvulsants;Carcinogenicity Tests;Carcinogens;chemically induced;Diethylnitrosamine;Dose-Response Relationship,Drug;genetics;Japan;Liver Neoplasms;mechanisms of carcinogenesis;metabolism;Mice;Mice,Transgenic;pathology;Phenobarbital;Research;toxicity;Transforming Growth Factor alpha;

  19. Effect of various antiepileptic drugs in zebrafish PTZ-seizure model

    Directory of Open Access Journals (Sweden)

    P Gupta

    2014-01-01

    Full Text Available Recently zebrafish larvae have emerged as a high-throughput model for screening pharmacological activities. The present study was undertaken to investigate the effect of established anticonvulsants, such as valproic acid, carbamazepine, gabapentin, diazepam, lacosamide and pregabalin against pentylenetetrazole (6 mM seizures in adult zebrafish. Different phases of seizures (increase swim activity, rapid whirlpool-like circling swim behaviour and brief clonus-like seizures leading to loss of posture were elicited in zebrafish on exposure for 15 min to 6 mM pentylenetetrazole. The exposure of zebrafish to an increasing concentration of the anticonvulsants alongside 6 mM pentylenetetrazole showed concentration-dependent elevation of seizure latency against pentylenetetrazole-induced seizures except for pregabalin, which failed to produce any anticonvulsant activity in zebrafish. Moreover the proconvulsant activity of caffeine was also evaluated using suboptimal concentration (4 mM of pentylenetetrazole in adult zebrafish. Decrease in seizure latency of different phases of seizures was observed with increasing concentration of caffeine compared with its respective control group. In view of the above findings, the results of the present study suggested that adult zebrafish produce the expected anticonvulsive and proconvulsive effects and could potentially be used as a screen in future epilepsy research.

  20. Chorea

    Science.gov (United States)

    ... levodopa, anti-convulsants, and anti-psychotics) metabolic and endocrine disorders, and vascular incidents. Is there any treatment? There ... dosages can treat drug-induced chorea. Metabolic and endocrine-related choreas are ... research on movement disorders such as chorea. The goals of this research ...

  1. Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and Older

    Science.gov (United States)

    ... close relative with history of fracture as an adult long-term low calcium intake inadequate physical activity current cigarette smoking alcoholism use of certain medications such as corticosteroids and anticonvulsants history of anorexia nervosa. What Is Osteoporosis? Osteoporosis is a disease that ...

  2. The Histone Deacetylase Inhibitor Valproic Acid Enhances Acquisition, Extinction, and Reconsolidation of Conditioned Fear

    Science.gov (United States)

    Bredy, Timothy W.; Barad, Mark

    2008-01-01

    Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its…

  3. Universelle kramper og respirationsstop som komplikation i forbindelse med lokalanalgesi ved circumcision

    DEFF Research Database (Denmark)

    Heiberg, Ida Louise; Nebrich, Lars; Pedersen, Pernille

    2015-01-01

    We present two cases in which two boys of four weeks and four and a half months, respectively, experienced seizures and respiratory insufficiency as complications to the local anaesthesia administered for ritual circumcision. They both needed intubation and anticonvulsive therapy and acquired an...

  4. Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice

    Directory of Open Access Journals (Sweden)

    Karadag C.H.

    2000-01-01

    Full Text Available We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20 produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

  5. Vitamin D deficiency is prevalent in girls and women with rett syndrome

    Science.gov (United States)

    The aim of the study was to determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D (25-(OH)D) levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in girls and women with Rett syndrome (RTT). Retrospective review of...

  6. Functional effects of the KCNQ modulators retigabine and XE991 in the rat urinary bladder

    DEFF Research Database (Denmark)

    Rode, Frederik; Svalø, Julie; Sheykhzade, Majid; Rønn, L. C B; Jakobsen, Julie Svalø

    The anticonvulsant retigabine has previously been reported to inhibit bladder overactivity in rats in vivo but the mechanism and site of action are not known. In the present study we investigated the effect of retigabine in isolated rat bladder tissue. Bladders from Sprague-Dawley rats were cut t...

  7. Effects of two GABA-B receptor agonists on cortical epileptic afterdischarges in immature rats are not identical

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Tabashidze, Nana

    Praha : The Czech Neuroscience Society, 2007. s. 34-34. [Conference of the Czech Neuroscience Society /6./. 19.11.2007-20.11.2007, Praha] R&D Projects: GA ČR(CZ) GA305/05/2581 Institutional research plan: CEZ:AV0Z50110509 Keywords : spr2 * GAGA-B receptor agonists * anticonvulsant effect * proconvulsant effect Subject RIV: FH - Neurology

  8. Landau-Kleffner Syndrome

    Science.gov (United States)

    ... parts of the brain that control comprehension and speech. The disorder usually occurs in children between the ages of 5 and 7 years. ... of medications, such as anticonvulsants and corticosteroids, and speech therapy, ... severe language disorder, while others may regain much of their language ...

  9. Nutritional Considerations for Severely Handicapped Children.

    Science.gov (United States)

    Sobsey, Dick

    Children and adults with severe disabilities may have nutritional problems due to the effects of the primary disability (including such syndromes as phenylketonuria, galactosemia, and Hurler's Disease), effects related to medications (including anticonvulsants, tranquilizers, and laxatives), effects of food preferences (restrictive food…

  10. Cytotoxic and anthelmintic potential of crude saponins isolated from Achillea Wilhelmsii C. Koch and Teucrium Stocksianum boiss

    OpenAIRE

    Ali Niaz; Shah Syed; Shah Ismail; Ahmed Ghayour; Ghias Mehreen; Khan Imran

    2011-01-01

    Abstract Background Saponins isolated from plant sources have a number of traditional and industrial applications. Saponins have pharmacological effects like anti-inflammatory, molluscicidal, antimicrobial, antispasmodic, antidiabetic, anticancer, anticonvulsant, anthelmintic, antitussive and cytotoxic activities. The current work describes the anthelmintic and cytotoxic activities of crude saponins of Achillea Wilhelmsii and Teucrium Stocksianum as these plants are rich with saponins. Method...

  11. Epilepsy in Adults with TSC

    Medline Plus

    Full Text Available ... for women using epilepsy drugs that affect the rate at which the liver metabolizes estrogen. The dosage for emergency contraception (morning after pill) will also depend on the type of anticonvulsant medication a woman takes. The use of barrier methods such as a diaphragm, sponges, ...

  12. Hypoglycemia-induced seizures following physical exercise in a man with type 1 diabetes and latent epilepsy

    OpenAIRE

    Marit R Bjorgaas

    2011-01-01

    A 42 year old solicitor suffered episodes of loss of consciousness in his late twenties before type 1 diabetes was diagnosed at the age of 32. After commencing insulin therapy, he experienced numerous hypoglycemia-induced seizures, all occurring in relation to exercise or consuming alcohol. Rationalization of his treatment with insulin and anticonvulsant medication has almost abolished the hypoglycemia-induced seizures.

  13. Ciradian dysrhythmias in the EEG of children with clonazepam treatment

    OpenAIRE

    Arbogast, B.; Hallek, M.; Arbogast, Helmut; Hellbrügge, T.; Schmid, R

    1984-01-01

    The effects of different anticonvulsants on the system of cir-cadian and ultradian rhythms in the EEG of children was investigated in ten 24*-h recordings of children with different forms of epilepsy. Circadian dysrhythmias could be found in children with Clonazepam treatment.

  14. Which drugs are contraindicated during breastfeeding? Practice guidelines.

    OpenAIRE

    Moretti, M. E.; Lee, A.; Ito, S.

    2000-01-01

    QUESTION: Many breastfeeding mothers are concerned about taking medications that might affect their babies. Are there any guidelines on which drugs are safe? ANSWER: Only a few drugs pose a clinically significant risk to breastfed babies. In general, antineoplastics, drugs of abuse, some anticonvulsants, ergot alkaloids, and radiopharmaceuticals should not be taken, and levels of amiodarone, cyclosporine, and lithium should be monitored.

  15. Pharmacologic treatment of pain in polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Jensen, Troels Staehelin

    2000-01-01

    Tricyclic antidepressants and anticonvulsants have become the mainstay in the treatment of pain in polyneuropathy. Within the last decade, controlled trials have shown that numerous other drugs relieve such pain. To estimate the efficacy of the different treatments, the authors identified all pla...

  16. NEUROPHARMACOLOGICAL EXPLORATION OF THUJA OCCIDENTALIS LINN.

    OpenAIRE

    Deb Lokesh; Dey Amitabha; Agrawal Sachin; Jain Avijeet

    2011-01-01

    In present study, oral administration of 100, 200 and 400 mg/kg doses of the aqueous extract of Thuja occidentalis Linn in rats and mice were evaluated for its anxiolytic, nootropic, anticonvulsant and motor coordination activity by using different animal models. The number of entries as well as the duration of stay in the open arms significantly increased (***p

  17. PHYTO-PHARMACOLOGICAL REVIEW OF ARGYREIA NERVOSA

    OpenAIRE

    Krishnaveni, A; T. Sant Rani

    2011-01-01

    Herbal medicines are the significant and reliable sources for treating various diseases. Argyreia nervosa is traditionally used in wound healing, syphilius,diuretics,rheumatic affections, leucohorrhoea.,cerebral disorders, ulcers, as anti-tumour and to prevent contraception.Phytoconstituents such as flavanoids, steroids, ergoline alkaloids and triterpenoids were identified. Pharmacological studies proved its anticonvulsant, immunomodulatory, hypotensive, anti- inflammatory and no...

  18. Argyreia speciosa (Linn. f.) sweet: A comprehensive review

    OpenAIRE

    Galani, V. J.; B G Patel; Patel, N B

    2010-01-01

    Argyreia speciosa (Linn. f.) Sweet is a popular Indian medicinal plant, which has long been used in traditional Ayurvedic Indian medicine for various diseases. This plant is pharmacologically studied for nootropic, aphrodisiac, immunomodulatory, hepatoprotective, antioxidant, antiinflammatory, antihyperglycemic, antidiarrheal, antimicrobial, antiviral, nematicidal, antiulcer, anticonvulsant, analgesic and central nervous depressant activities. A wide range of phytochemical constituents have b...

  19. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report

    OpenAIRE

    Sriratanaviriyakul, Narin; Nguyen, Lam-Phuong; Henderson, Mark C.; Timothy E Albertson

    2014-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflam...

  20. 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.

  1. 77 FR 12309 - Determination That PHENURONE (Phenacemide) Tablet, 500 Milligrams, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2012-02-29

    ... Abbott Laboratories, and initially approved on June 28, 1951. PHENURONE is an oral anticonvulsant indicated for the treatment of epilepsy. In a letter dated May 14, 2003, Abbott Laboratories requested withdrawal of NDA 007707 for PHENURONE (phenacemide) Tablet. In the Federal Register of May 5, 2004 (69...

  2. Pain

    Science.gov (United States)

    ... pre-gaB-uh-lin) and other anticonvulsant medicines • sleeping longer and better by changing bedtime and sleep habits or using medicines to help you sleep • low-impact physical activity, such as walking or swimming • reducing stress • massage If you have ...

  3. Aspirin induced fixed drug eruptions: a case report

    Directory of Open Access Journals (Sweden)

    Rama R. Bhosale

    2013-04-01

    Full Text Available Fixed drug eruptions are common cutaneous adverse drug reactions, commonly caused by anticonvulsants, antibiotics and analgesics. Here, we report a case of a 27-year-old male of fixed drug eruptions due to Aspirin which was used in treatment of headache. [Int J Basic Clin Pharmacol 2013; 2(2.000: 220-221

  4. Medication Use among Australian Adults with Intellectual Disability in Primary Healthcare Settings: A Cross-Sectional Study

    Science.gov (United States)

    Doan, Tan N.; Lennox, Nicholas G.; Taylor-Gomez, Miriam; Ware, Robert S.

    2013-01-01

    Background: There is concern about widespread medication use by people with intellectual disability (ID), especially psychotropic and anticonvulsant agents. However, there is sparse information on prescribing patterns in Australia. Method: This cross-sectional study was conducted between 2000 and 2002 among adults with ID who live in the community…

  5. Stevens–Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

    OpenAIRE

    Ajay Kumar; Sukanto Sarkar; Samir Kumar Praharaj; Sayeed Akhtar; Diwakar, M.

    2011-01-01

    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.

  6. GABA System Dysfunction in Autism and Related Disorders: From Synapse to Symptoms

    OpenAIRE

    Coghlan, Suzanne; Horder, Jamie; Inkster, Becky; Mendez, M. Andreina; Murphy, Declan G; Nutt, David J

    2012-01-01

    Autism Spectrum Disorders (ASDs) are neurodevelopmental syndromes characterised by repetitive behaviours and restricted interests, impairments in social behavior and relations, and in language and communication. These symptoms are also observed in a number of developmental disorders of known origin, including Fragile X Syndrome, Rett syndrome, and Fetal Anticonvulsant Syndrome. While these conditions have diverse etiologies, and poorly understood pathologies, emerging evidence suggests that t...

  7. 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....

  8. Toxic encephalopathy in a child after brief exposure to insect repellents.

    OpenAIRE

    Roland, E H; Jan, J. E.; Rigg, J M

    1985-01-01

    Seizures and acute behaviour change developed in an 8-year-old girl following exposure to Muskol and Off insect repellents. She recovered within 3 days with supportive treatment, including anticonvulsant medication. The assumed toxic agent was N,N-diethyltoluamide.

  9. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    X. Qiao

    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

  10. Review on plants with CNS-effects used in traditional South African medicine against mental diseases

    DEFF Research Database (Denmark)

    Stafford, Gary Ivan; Pedersen, Mikael Egebjerg; van Staden, Johannes;

    2008-01-01

    -related dementia and debilitative mental disorders. Details of the recent scientific studies conducted on some of these plants are reviewed. Extracts of Searsia chirindensis, Cotelydon orbiculata and Leonotis leonurus have shown in vivo anticonvulsant activity. Extracts from Searsia dentata and Searsia pyroides...

  11. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix;

    2005-01-01

    neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment...

  12. Synthesis of carbon-14 analogue of 1,5 diaryl-5-[14C]-1,2,3-triazoles

    International Nuclear Information System (INIS)

    Two 1,2,3-triazole anticonvulsants, 1-(4-methylsulfone-phenyl)-5-(4-methyl-phenyl)-1,2,3-triazole and 1-(4-methylsulfone-phenyl)-5-phenyl-1,2,3-triazole, both labeled with carbon-14 in the 5-position were prepared from para-tolunitrile-[cyano-14C] and benzonitrile-[cyano-14C], respectively

  13. 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.

  14. The wide pharmacological versatility of semicarbazones, thiosemicarba-zones and their metal complexes.

    Science.gov (United States)

    Beraldo, Heloisa; Gambino, Dinorah

    2004-01-01

    The more significant bioactivities of a variety of semicarbazones (anti-protozoa, anticonvulsant) and thiosemicarbazones (antibacterial, antifungal, antitumoral, antiviral) and their metal complexes are reviewed together with proposed mechanisms of action and structure-activity relationships. Clinical or potential pharmacological applications of these versatile compounds are discussed. PMID:14754441

  15. Óleos essenciais com propriedades anticonvulsivantes

    OpenAIRE

    Reinaldo De Almeida Nóbrega; Simone Cristina Motta; José Roberto Leite

    2003-01-01

    Óleos essenciais com propriedades anticonvulsivantes (Aceites esenciales con propiedades anticolvulsivantes - Oil essen-tial with anticonvulsivants properties): The present study constitutes a systematic review of various plantderived essentials oils with anticonvulsant activity in different parts of the world, including Brazil

  16. Antiepileptic drugs in neuroprotection

    Czech Academy of Sciences Publication Activity Database

    Pitkanen, A.; Kubová, Hana

    2004-01-01

    Roč. 5, č. 4 (2004), s. 777-798. ISSN 1465-6566 R&D Projects: GA MZd NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : antiepileptic drugs * anticonvulsant * epilepsy Subject RIV: FH - Neurology

  17. The potential of sec-butylpropylacetamide (SPD) and valnoctamide and their individual stereoisomers in status epilepticus.

    Science.gov (United States)

    Shekh-Ahmad, Tawfeeq; Mawasi, Hafiz; McDonough, John H; Yagen, Boris; Bialer, Meir

    2015-08-01

    sec-Butylpropylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a chiral constitutional isomer of valproic acid's (VPA) corresponding amide--valpromide. Racemic-SPD and racemic-VCD possess a unique and broad-spectrum antiseizure profile superior to that of VPA. In addition, SPD blocks behavioral and electrographic status epilepticus (SE) induced by pilocarpine and the organophosphates soman and paraoxon. Valnoctamide has similar activity as SPD in the soman-induced SE model. The activity of SPD and VCD against SE is superior to that of diazepam and midazolam in terms of rapid onset, potency, and ability to block SE when given 20 to 60 min after seizure onset. sec-Butylpropylacetamide and VCD possess two stereogenic carbons in their chemical structure and, thus, exist as a racemic mixture of four individual stereoisomers. The anticonvulsant activity of the individual stereoisomers of SPD and VCD was comparatively evaluated in several anticonvulsant rodent models including the benzodiazepine-resistant SE model. sec-Butylpropylacetamide has stereoselective pharmacokinetics (PK) and pharmacodynamics (PD). The higher clearance of (2R,3S)-SPD and (2S,3R)-SPD led to a 50% lower plasma exposure and, consequently, to a lower anticonvulsant activity compared to racemic-SPD and its two other stereoisomers. Racemic-SPD, (2S,3S)-SPD, and (2R,3R)-SPD have similar anticonvulsant activities and PK profiles that are better than those of (2R,3S)-SPD and (2S,3R)-SPD. Valnoctamide has a stereoselective PK with (2S,3S)-VCD exhibiting the lowest clearance and, consequently, a twice-higher plasma exposure than all other stereoisomers. Nevertheless, there was less stereoselectivity in VCD anticonvulsant activity, and each stereoisomer had similar ED50 values in most models. sec-Butylpropylacetamide and VCD stereoisomers did not cause teratogenicity (i.e., neural tube defect) in mice at doses 3-12 times higher than their anticonvulsant-ED50 values. This article is part of a

  18. Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

    Directory of Open Access Journals (Sweden)

    Adriana Monserrath Orellana-Paucar

    Full Text Available In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ. In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf] in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

  19. Transient Pseudohypoparathyroidism Manifested as Recurrent Convulsion in a Neonate

    Directory of Open Access Journals (Sweden)

    Archan Sil

    2015-06-01

    Full Text Available We report case of a neonate who presented with recurrent seizure attacks at the age of 12 days. The baby was managed with anticonvulsant drugs. Eighteen days later, the neonate had repeated episodes of convulsion and was referred to our clinic. During initial work-up, we detected hypocalcaemia and started calcium supplementation along with anticonvulsants. There was another episode of convulsion after 3 days, which prompted us to do a repeat serum calcium assay. It showed hypocalcaemia which was persistent and resistant to calcium supplementation. On further investigation, hyperphosphatemia and raised concentration of parathyroid hormone were detected. Serum magnesium and 25(OHD level was normal. We suspected pseudohypoparathyroidism-and-hypocalcaemia was managed with calcium and vitamin D therapy. There was no further episode of convulsion and the baby was stable with corrected serum calcium and phosphorus levels during follow-up. Turk Jem 2015; 19: 65-66

  20. 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 and an...... increase in severity with time. Recurrence of episodes in bipolar disorders is suggested to reflect a process of sensitization. Repeated intermittent administration of amphetamine in rodents gives rise to a behavioral sensitization phenomena argued to have similarities to the sensitization found in humans....... The aims were therefore to explore the predictive validity of the amphetamine sensitization model as a behavioral model of mania by testing the effect of a range of antimanic drugs and to evaluate the effect of retigabine on the sensitized amphetamine response. Furthermore, since withdrawal from...

  1. 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......, significantly and dose-dependently attenuates the induced hyperactivity at a lowest effective dose of 1.0 mg/kg, whereas basal locomotor activity is reduced only at doses 4.0 mg/kg. In conclusion, retigabine was found to have an antimanic-like effect in the AMPH+CDP-induced hyperactivity model, suggesting a...

  2. Mechanisms and pharmacology of neuropathic pain in multiple sclerosis.

    Science.gov (United States)

    Iannitti, T; Kerr, B J; Taylor, B K

    2014-01-01

    The neuropathic pain of multiple sclerosis is quite prevalent and severely impacts quality of life. A few randomized, placebo-controlled, blinded clinical trials suggest that cannabis- and anticonvulsant-based treatments provide partial pain relief, but at the expense of adverse events. An even smaller, but emerging, number of translational studies are using rodent models of experimental autoimmune encephalomyelitis (EAE), which exhibit pain-like behaviors resembling those of Multiple sclerosis (MS) patients. These studies not only support the possible effectiveness of anticonvulsants, but also compel further clinical trials with serotonin-norepinephrine reuptake inhibitors, the immunosuppressant drug rapamycin, or drugs which interfere with glutamatergic neurotransmission. Future behavioral studies in EAE models are essential toward a new pharmacotherapy of multiple sclerosis pain. PMID:24590824

  3. Fetal valproate syndrome

    Directory of Open Access Journals (Sweden)

    Parmarth G Chandane

    2014-01-01

    Full Text Available Antenatal use of anticonvulsant valproic acid can result in a well-recognized cluster of facial dysmorphism, congenital anomalies and neurodevelopmental retardation. In this report, we describe a case with typical features of fetal valproate syndrome (FVS. A 26-year-old female with epilepsy controlled on sodium valproate 800 mg/day since 3 years, gave birth to a male child with characteristic features of FVS. She also had 3 spontaneous first-trimester abortions during those 3 years. Sodium valproate, a widely used anticonvulsant and mood regulator, is a well-recognized teratogen that can result in facial dysmorphism, craniosynostosis, neural tube defects, and neurodevelopmental retardation. Therefore, we strongly recommend avoidance of valproic acid and supplementation of folic acid during pregnancy.

  4. Neurological Complications of Pregnancy.

    Science.gov (United States)

    Block, H Steven

    2016-07-01

    Physiologic alterations during pregnancy create an environment for the occurrence of disease states that are either unique to pregnancy, occur more frequently in pregnancy, or require special management considerations that may be different from the nonpregnancy state. In the realm of cerebrovascular disease, preeclampsia, eclampsia, reversible cerebral vasoconstriction syndrome, sources of cardiogenic embolization including peripartum cardiomyopathy, cerebral venous thrombosis, pituitary apoplexy, subarachnoid hemorrhage, intracerebral hemorrhage, and special considerations for anticoagulation during pregnancy will be discussed. Management of epilepsy during pregnancy counterbalances maternal freedom from seizures against the potential for major, minor, cognitive, and behavioral fetal deformities. Teratogenic potential of the most common anticonvulsants are described. Considerations for anticonvulsant level monitoring during pregnancy are based upon differences in medication clearance in comparison to the prepregnancy state. The most common neuromuscular disorders of pregnancy are reviewed. PMID:27230113

  5. Osthole suppresses seizures in the mouse maximal electroshock seizure model.

    Science.gov (United States)

    Luszczki, Jarogniew J; Andres-Mach, Marta; Cisowski, Wojciech; Mazol, Irena; Glowniak, Kazimierz; Czuczwar, Stanislaw J

    2009-04-01

    The aim of this study was to determine the anticonvulsant effects of osthole {[7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one]--a natural coumarin derivative} in the mouse maximal electroshock-induced seizure model. The antiseizure effects of osthole were determined at 15, 30, 60, and 120 min after its systemic (i.p.) administration. Time course of anticonvulsant action of osthole revealed that the natural coumarin derivative produced a clear-cut antielectroshock activity in mice and the experimentally-derived ED(50) values for osthole ranged from 259 to 631 mg/kg. In conclusion, osthole suppresses seizure activity in the mouse maximal electroshock-induced seizure model. It may become a novel treatment option following further investigation in other animal models of epilepsy and preclinical studies. PMID:19236860

  6. Mood-stabilizing pharmacological treatment in bipolar disorders and risk of suicide

    DEFF Research Database (Denmark)

    Søndergård, Lars; Lopez, A.G.; Andersen, Per Kragh; Kessing, L.V.

    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 w...... similar reduction in the rate of suicide, the results suggest that treatment with lithium may have some superiority in relation to prevention of suicide Udgivelsesdato: 2008......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 was...... investigated among all patients discharged nationwide from hospital psychiatry as an in- or outpatient in a period from 1995 to 2000 in Denmark with a diagnosis of BD. Results: A total of 5,926 patients were included in the study and among these 51 patients committed suicide eventually during the study period...

  7. Neuropsychological assessment of chronic non-malignant pain patients treated in a multidisciplinary pain centre

    DEFF Research Database (Denmark)

    Sjøgren, Per; Christrup, Lona Louring; Petersen, Morten Aa;

    2005-01-01

    The aim of the study was to investigate the influence of pain, sedation, pain medications and socio-demographics on cognitive functioning in chronic non-malignant pain patients. Chronic non-malignant pain patients (N=91) treated in a multidisciplinary pain centre were compared with age and sex...... matched healthy volunteers (N=64). Furthermore four subgroups of patients were examined: Group 1 (N=21) received no pain medications, group 2 (N=19) were in long-term oral opioid treatment, group 3 (N=18) were treated with antidepressants and/or anticonvulsants and group 4 (N=33) were treated with a...... combination of long-term oral opioids and antidepressants and/or anticonvulsants. Assessments comprised pain (PVAS) and sedation (SVAS), Continuous Reaction Time (CRT) testing for sustained attention, Finger Tapping Test (FTT) testing for psychomotor speed, Paced Auditory Serial Addition Task (PASAT) testing...

  8. Tic Douloureux

    Directory of Open Access Journals (Sweden)

    John D Loeser

    2001-01-01

    Full Text Available Tic douloureux is an excruciatingly painful condition that primarily affects elderly people. It consists of unilateral electric shock-like facial pains triggered by non-noxious stimulation with clear-cut pain-free intervals. It should be discriminated from all other types of facial pain by the history and physical examination. Primary treatment includes anticonvulsant drugs if these fail or side effects prevent their use, a surgical procedure is warranted. Almost every patient with tic douloureux can be relieved of his or her pain with anticonvulsant medications or surgery. Stereotactic radiosurgery, percutaneous gangliolysis and suboccipital craniectomy with microvascular decompression are the primary surgical options. The common aspects of tic douloureux and some of the rarer variations are reviewed, and treatment options are presented.

  9. Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: A retrospective study of causative drugs and clinical outcome

    Directory of Open Access Journals (Sweden)

    Sharma Vinod

    2008-01-01

    Full Text Available Background and Aims: Stevens Johnson syndrome (SJS, toxic epidermal necrolysis (TEN and SJS-TEN overlap are serious adverse cutaneous drug reactions. Drugs are often implicated in these reactions. Methods: A retrospective analysis of inpatients′ data with these dermatological diagnoses were carried out for three years, to study the causative drugs, clinical outcome, and mortality in these conditions. Results: Thirty patients (15 TEN, nine SJS-TEN overlap, and six SJS were admitted. In 21 cases, multiple drugs were implicated whereas single drugs were responsible in nine. Anticonvulsants (35.08% were the most commonly implicated drugs followed by antibiotics (33.33% and NSAIDS (24.56%. Twenty-five patients recovered whereas five died (four TEN, one SJS-TEN overlap. Conclusion: Anticonvulsants, antibiotics and NSAIDs were the most frequently implicated drugs. TEN causes higher mortality than both SJS and SJS-TEN overlap.

  10. Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy

    International Nuclear Information System (INIS)

    The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks. Four cases are described of adverse reactions of phenytoin during the cocomitant use of cranial radiotherapy. In one patient this proved fatal. There is increasing anecdotal support in the literature for a synergistic effect between phenytoin therapy and cranial radiotherapy that can result in the life-threatening Stevens-Johnson syndrome. While the association is uncommon, four cases within 24 months in one department suggest that the routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures may not be warranted, particularly if the patient is to receive cranial radiotherapy. (orig.)

  11. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin

    International Nuclear Information System (INIS)

    In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder is probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice

  12. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.

    Science.gov (United States)

    Damar, U; Gersner, R; Johnstone, J T; Schachter, S; Rotenberg, A

    2016-06-01

    Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity. PMID:27086593

  13. Goldenhar syndrome, anterior encephalocele, and aqueductal stenosis following fetal primidone exposure.

    Science.gov (United States)

    Gustavson, E E; Chen, H

    1985-08-01

    Fetal exposure to primidone was associated with Goldenhar syndrome, hemifacial microsomia, tetralogy of Fallot, aqueductal stenosis, and anterior encephalocele in this male infant. No similar cases in anticonvulsant-exposed pregnancies were found on literature review, despite the increased incidence of other anomalies following such exposure. Goldenhar syndrome, especially related to rare central nervous system anomalies, is reviewed. Experimental production of hemifacial microsomia by a folic acid antagonist, triaxene, is mediated via hemorrhage in the fetus. Intraventricular hemorrhage was noted in this infant as were dilated lateral and third ventricles. The hemorrhagic diathesis and/or the folic acid depletion of newborns following fetal anticonvulsant exposure may have been the underlying mechanism. PMID:4035586

  14. Carbamazepine overdose after exposure to simethicone: a case report

    OpenAIRE

    Guneysel Ozlem; Onur Ozge; Denizbasi Arzu; Saritemur Murat

    2008-01-01

    Abstract Introduction Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine. Case presentation We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twi...

  15. Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice

    DEFF Research Database (Denmark)

    Lehre, A C; Rowley, N M; Zhou, Y;

    2011-01-01

    the GAT1 by the clinically available anti-epileptic drug tiagabine has been an effective strategy for the treatment of some patients with partial seizures. Recently, the investigational drug EF1502, which inhibits both GAT1 and BGT1, was found to exert an anti-convulsant action synergistic to that of...... the control of seizure susceptibility and cannot provide a mechanistic understanding of the synergism that has been previously reported with tiagabine and EF1502....

  16. NEW DERIVATIVES OF 2-R1-N-(5-R)-1,3,4-THIADIAZOL-2-YL-BENZOLSULFONAMIDES: SYNTHESIS, PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY PREDICTION

    OpenAIRE

    Sych I.V.; Perekhoda L.О.; Іеremina Z.G.

    2015-01-01

    Introduction: The analysis of modern literature, including overseas one, showed that a lot of the scientific researches is devoted to finding and creating biologically active compounds on base 1,3,4-thiadiazole. Derivatives of 1,3,4-thiadiazole are the large group of heterocyclic compounds with high rates of antimicrobial, antituberculosis, antidiabetic, antineoplastic and anticonvulsant activity. Material and methods: The purpose of this study was the expansion of sulfone derivati...

  17. Acute isoniazid intoxication: case report

    OpenAIRE

    Dilek Altun; Halil Cetingok; Gulay AsIk Eren; Zafer Cukurova; Oya Hergunsel

    2015-01-01

    Isoniazid is a bactericidal antituberculosis drug, used commonly for treatment and prophylaxis of tuberculosis. Acute isoniazid intoxication is characterized by a clinical triad consisting of metabolic acidosis with a high anion gap resistant to treatment with sodium bicarbonate, seizures which may be fatal and refractory to standard anticonvulsant therapy, and coma. Pyridoxine, in a dose equivalent to the amount of isoniasid ingested, is the only effective antidote. Here, we reported a 14 ye...

  18. Montelukast reduces seizures in pentylenetetrazol-kindled mice

    OpenAIRE

    Fleck, J.; F.R. Temp; Marafiga, J.R.; A.C. Jesse; Milanesi, L.H.; L.M. Rambo; C.F. Mello

    2016-01-01

    Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Mon...

  19. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy

    OpenAIRE

    Bagci, S.; Zschocke, J.; Hoffmann, G F; Bast, T.; Klepper, J; Müller, A.; Heep, A; Bartmann, P.; Franz, A R

    2009-01-01

    Pyridox(am)ine-5′-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5′-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unrespons...

  20. Antimicrobial activity against Helicobacter pylori strains and antioxidant properties of blackberry leaves (Rubus ulmifolius) and isolated compounds

    OpenAIRE

    2009-01-01

    Abstract Rubus spp. (Rosaceae) provide extracts used in traditional medicine as antimicrobial, anticonvulsant, muscle relaxant and radical scavenging agents. Resistance to antibiotics used to treat Helicobacter pylori infection as well as their poor availability in developing countries prompted us to test the antimicrobial activity of Rubus ulmifolius leaves and isolated polyphenols against two H. pylori strains with different virulence (CagA+ strain 10K and CagA? strain G21). The ...

  1. Hypoglycemia-induced seizures following physical exercise in a man with type 1 diabetes and latent epilepsy

    Directory of Open Access Journals (Sweden)

    Marit R Bjorgaas

    2011-01-01

    Full Text Available A 42 year old solicitor suffered episodes of loss of consciousness in his late twenties before type 1 diabetes was diagnosed at the age of 32. After commencing insulin therapy, he experienced numerous hypoglycemia-induced seizures, all occurring in relation to exercise or consuming alcohol. Rationalization of his treatment with insulin and anticonvulsant medication has almost abolished the hypoglycemia-induced seizures.

  2. Transection spinale et injection intrathécale de BDNF : deux modèles pertinents de douleur neuropathique chez le rat ?

    OpenAIRE

    M'Dahoma, Saïd

    2013-01-01

    Neuropathic pain, caused by lesions of central or peripheral nervous system, is difficult to treat because of its resistance to classical antalgic treatments. Most of pharmacotherapeutic treatments of neuropathic pain (antidepressants, anticonvulsants) currently used are only based on empirical data and are not specifically aimed at relieving pain. Better knowledge of the mechanisms underlying neuropathic pain is an absolute prerequesite to develop new and innovative treatments. With the aim ...

  3. Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines

    OpenAIRE

    Spurny, R.; Ramerstorfer, J.; Price, K; Brams, M.; M. Ernst; Nury, H.; Verheij, M.; Legrand, P.; Bertrand, D.; Bertrand, S.; Dougherty, D A; de Esch, I. J. P.; Corringer, P.-J.; Sieghart, W.; Lummis, S. C. R.

    2012-01-01

    GABA_A receptors are pentameric ligand-gated ion channels involved in fast inhibitory neurotransmission and are allosterically modulated by the anxiolytic, anticonvulsant, and sedative-hypnotic benzodiazepines. Here we show that the prokaryotic homolog ELIC also is activated by GABA and is modulated by benzodiazepines with effects comparable to those at GABA_A receptors. Crystal structures reveal important features of GABA recognition and indicate that benzodiazepines, depending on their conc...

  4. Ketogenic diet and epilepsy: an up-date review

    OpenAIRE

    Verrotti, Alberto; Pascotto, Antonio; Operto, Francesca; FORTUNATO, Delia; Rita Della CORTE; Coppola, Giangennaro; Alfredo D'Aniello

    2009-01-01

    Background and Aims: Ketogenic diet is currently a therapeutic option for the treatment of epilepsy other than anticonvulsant drugs, for which there is a growing interest in Europe and worldwide, mainly due to the persisting number of refractory patients and the adverse side effects of antiepileptic old and new drugs. Aim of the present article is to review literature data regarding the use of the diet in the different types of epilepsies and epilepsy syndromes, trying to better understand th...

  5. Ketogenic Diets: Evidence for Short and Long-term Efficacy

    OpenAIRE

    Kossoff, Eric H.; Rho, Jong M

    2009-01-01

    The use of dietary treatments for epilepsy (ketogenic, modified Atkins, and low glycemic index diets) has been in continuous use since 1921. These treatments have been well-studied in the short-term, with approximately 50% of children having at least a 50% reduction in seizures after 6 months. Approximately one-third will have >90% reduction in their seizures as well. Animal studies confirm these findings, with broad evidence demonstrating the diet's acute anticonvulsant effects. In addition,...

  6. Dietary Approaches to Epilepsy Treatment: Old and New Options on the Menu

    OpenAIRE

    Stafstrom, Carl E.

    2004-01-01

    Dietary therapies represent a potentially valuable adjunct to other epilepsy treatments, such as anticonvulsant medications, epilepsy surgery, and vagus nerve stimulation. Although the ketogenic diet (high fat, adequate protein, low carbohydrate) is the most well-established dietary therapy for epilepsy, other possible approaches include the Atkins diet (high fat, high protein, low carbohydrate), a diet enriched in polyunsaturated fatty acids, or overall restriction of calorie intake. This re...

  7. Biological Aspects of Emerging Benzothiazoles: A Short Review

    OpenAIRE

    Ruhi Ali; Nadeem Siddiqui

    2013-01-01

    In recent years heterocyclic compounds analogues and derivatives have attracted wide attention due to their useful biological and pharmacological properties. Benzothiazole is among the usually occurring heterocyclic nuclei in many marine as well as natural plant products. Benzothiazole is a privileged bicyclic ring system with multiple applications. It is known to exhibit a wide range of biological properties including anticancer, antimicrobial, and antidiabetic, anticonvulsant, anti-inflamma...

  8. New Methodology for the Synthesis of Thiobarbiturates Mediated by Manganese(III Acetate

    Directory of Open Access Journals (Sweden)

    Patrice Vanelle

    2012-04-01

    Full Text Available A three step synthesis of various thiobarbiturate derivatives 17–24 was established. The first step is mediated by Mn(OAc3, in order to generate a carbon-carbon bond between a terminal alkene and malonate. Derivatives 1–8 were obtained in moderate to good yields under mild conditions. This key step allows synthesis of a wide variety of lipophilic thiobarbiturates, which could be tested for their anticonvulsive or anesthesic potential.

  9. Shellfish Toxins Targeting Voltage-Gated Sodium Channels

    OpenAIRE

    Fan Zhang; Xunxun Xu; Tingting Li; Zhonghua Liu

    2013-01-01

    Voltage-gated sodium channels (VGSCs) play a central role in the generation and propagation of action potentials in excitable neurons and other cells and are targeted by commonly used local anesthetics, antiarrhythmics, and anticonvulsants. They are also common targets of neurotoxins including shellfish toxins. Shellfish toxins are a variety of toxic secondary metabolites produced by prokaryotic cyanobacteria and eukaryotic dinoflagellates in both marine and fresh water systems, which can acc...

  10. The Impact of Open Access to Atypical Antipsychotics on Treatment Costs for Medi-Cal Patients with Bipolar Disorder

    OpenAIRE

    Sangeeta Narayan; Kimberly L. Sterling; McCombs, Jeffrey S.

    2006-01-01

    Background: The California Medicaid Program (Medi-Cal) provided open access to atypical antipsychotics in October 1997. This study investigated the impact of open access to atypical antipsychotics on the costs and duration of therapy for patients with bipolar disorders. Methods: Paid claims data from Medi-Cal were used to identify episodes of treatment using antipsychotics, antidepressants, mood stabilizers, or selected anticonvulsants initiated by patients with bipolar disorders. Episodes of...

  11. Mechanisms and Pharmacology of Neuropathic Pain in Multiple Sclerosis

    OpenAIRE

    Iannitti, T; Kerr, B.J.; Taylor, BK

    2014-01-01

    The neuropathic pain of multiple sclerosis is quite prevalent and severely impacts quality of life. A few randomized, placebo-controlled, blinded clinical trials suggest that cannabis- and anticonvulsant-based treatments provide partial pain relief, but at the expense of adverse events. An even smaller, but emerging, number of translational studies are using rodent models of experimental autoimmune encephalomyelitis (EAE), which exhibit pain-like behaviors resembling those of MS patients. The...

  12. Anaesthetic management of nesidioblastosis in a newborn.

    OpenAIRE

    Soares A.; Karapurkar S; Suresh S.

    1996-01-01

    This report details the management of a newborn with nesidioblastosis who underwent a 95% pancreatectomy under general anaesthesia. The baby presented with hypoglycemic convulsions, due to hyperinsulinism, and was treated with 12.5% dextrose infusions, glucagon and anticonvulsants. Intraoperatively and postoperatively the baby remained hyperglycemic. A postoperative osmotic diuresis necessitated the use of insulin for brief period. The infant remained euglycemic and convulsion f...

  13. [GABA-ergic system in defense against excitatory kynurenines].

    Science.gov (United States)

    Lapin, I P

    1997-01-01

    Protection against the excitatory action of L-kynurenine and quinolinic acid in mice is related to the activation of GABA-B and dopamine receptors of the brain and to much lesser degree to the activation of GABA-A receptors. It is hardly believable that the anticonvulsant effect of phenibut (beta-phenyl-GABA), baclofen (CL-phenibut), sodium hydroxybutyrate and taurine against seizures induced by these two kynurenines is determined by alterations in metabolism of GABA. PMID:9503572

  14. Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology

    OpenAIRE

    Jagdale, Swati C.; Ajay S. Bhadoriya; Chabukswar, Aniruddha R.

    2012-01-01

    Clonazepam (CLZ) is an anticonvulsant benzodiazepine widely used in the treatment of epilepsy. CLZ is a BCS Class II drug and its bioavailability is thus dissolution limited. The objective of the present study was to prepare solid dispersions (SDs) of CLZ by various techniques, using the amphiphilic carrier Gelucire 50/13 in various proportions, to increase its water solubility. Drug-polymer interactions were investigated by Fourier-transform infrared (FTIR) and UltraV...

  15. Endocrine abnormalities in human temporal lobe epilepsy.

    OpenAIRE

    Gallagher, B. B.

    1987-01-01

    Patients with temporal lobe epilepsy secrete ACTH at higher rates and in greater amounts than normal subjects. Temporal lobectomy restores ACTH secretion to normal amounts and rates. The ACTH secretion in temporal lobe epilepsy is independent of anticonvulsant drug effect and seizure frequency. Electrical stimulation of medial temporal lobe structures in patients with temporal lobe epilepsy affected ACTH secretion in a manner consistent with the hypothesis that ACTH secretion is regulated by ...

  16. Tuberous sclerosis: case report and investigation of family members

    OpenAIRE

    Wilson, R. Douglas; Hall, Judith G.; McGillivray, Barbara C

    1985-01-01

    Familial tuberous sclerosis probably occurs more often than is indicated by the literature: many family members show signs of being carriers of the gene for the disease when carefully examined. This article reports on a family with documented tuberous sclerosis in three generations and discusses the examination and investigation of at-risk family members, including the newborn, for signs of the disease. The potential teratogenic effects of anticonvulsants, used to control seizures in tuberous...

  17. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

    OpenAIRE

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both ...

  18. Baclofen overdose.

    OpenAIRE

    Lipscomb, D J; Meredith, T. J.

    1980-01-01

    A 57-year-old woman suffering from multiple sclerosis took an estimated 1500 mg of baclofen. She became deeply unconscious with generalized flaccid muscle paralysis and absent tendon reflexes. Toxicological analysis confirmed the presence of baclofen together with small amounts of paracetamol and glutethimide. Supportive therapy, including assisted ventilation for 3 days, led to complete recovery; anticonvulsant drugs were necessary for the treatment of grand mal fits. The clinical features a...

  19. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS)

    OpenAIRE

    Shaman Gill; Amitabh Sagar; Shankar, S.; Velu Nair

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, ...

  20. Synthesis of New Imidazolidin-2,4-dione and 2-Thioxoimidazolidin-4-ones via C-Phenylglycine Derivatives

    OpenAIRE

    José Alixandre de Sousa Luis; José Maria Barbosa Filho; Bruno Freitas Lira; Isac Almeida Medeiros; Liana Clébia Soares Lima de Morais; Alexsandro Fernandes dos Santos; Cledualdo Soares de Oliveira; Petrônio Filgueiras de Athayde-Filho

    2009-01-01

    Hydantoins and their derivatives constitute a group of pharmaceutical compounds with anticonvulsant and antiarrhythmic properties, and are also used against diabetes. N-3 and C-5 substituted imidazolidines are examples of such products. As such, we have developed a synthesis of 2,4-dione and 2-thioxo-4-one imidazolidinic derivatives by reaction of amino acids with C-phenylglycine, phenyl isocyanate and phenyl isothiocyanate. Four amino-derivatives IG(1-4) and eight imidazolidinic derivatives,...

  1. THE EFFECT OF NIGELLA SATIVA L. ON INTRACTABLE PEDIATRIC SEIZURES

    OpenAIRE

    J Akhondian; Parsa, A; H. RAKHSHANDE

    2009-01-01

    Background:Despite availability and administration of numerous antiepileptic drugs (AEDs) nearly 15% of childhood epilepsy cases are resistant to treatment; in traditional medicine however Nigella sativa L. (Black seed) has been known for its anticonvulsant effects.Materials and Methods:In this double-blind clinical trial conducted on children with refractory epilepsy we administered the aqueous extract of black seed as an adjunct therapy and compared the effects with those of a placebo. The ...

  2. Ozone oxidation of antidepressants in wastewater –Treatment evaluation and characterization of new by-products by LC-QToFMS

    OpenAIRE

    Lajeunesse André; Blais Mireille; Barbeau Benoît; Sauvé Sébastien; Gagnon Christian

    2013-01-01

    Abstract Background The fate of 14 antidepressants along with their respective N-desmethyl metabolites and the anticonvulsive drug carbamazepine was examined in a primary sewage treatment plant (STP) and following advanced treatments with ozone (O3). The concentrations of each pharmaceutical compound were determined in raw sewage, effluent and sewage sludge samples by LC-MS/MS analysis. The occurrence of antidepressant by-products formed in treated effluent after ozonation was also investigat...

  3. Ali je uporaba kognitivnih modulatorjev smiselna pri zdravljenju bipolarne motnje razpoloženja?: Is the use of cognitive modulators reasonable in treatment of bipolar mood disorder?:

    OpenAIRE

    Dernovšek, Mojca Zvezdana; Kržišnik, Julija

    2011-01-01

    A significant proportion of patients with bipolar disorder do not respond satisfactorily to conventional pharmacological treatment with lithium, anticonvulsants, antipsychotics and antidepressants. Several studies point to high risk for chronic illness and relapse despite receiving available therapy.At this moment we do not even have a common definition for treatment-resistant bipolar disorder, which makes assessing the number of patients refractory to treatment very difficult. Not only resis...

  4. A critical review of the recent literature and selected therapy guidelines since 2006 on the use of lamotrigine in bipolar disorder

    OpenAIRE

    Tränkner A; Sander C.; Schönknecht P

    2013-01-01

    Anja Tränkner, Christian Sander, Peter SchönknechtDepartment of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, GermanyAbstract: The anticonvulsant drug lamotrigine (LTG), a sodium channel blocker and inhibitor of glutamate release, has been found to have antidepressant effects in the treatment of bipolar disorder. It is recommended by certain therapy guidelines as a first-line agent for acute and maintenance therapy in bipolar depression, but there have ...

  5. Unilateral periventricular heterotopia and epilepsy in a girl with Ehlers–Danlos syndrome

    Directory of Open Access Journals (Sweden)

    Salvatore Savasta

    2015-01-01

    Conclusion: To our knowledge, this is the first report of unilateral periventricular heterotopia associated with Ehlers–Danlos syndrome. We first hypothesized a mosaicism as the cause of both, a unilateral localization of the heterotopias and a favorable long-term course with good response to anticonvulsant therapy; however, intriguingly, we could not demonstrate a mosaicism as the genetic condition in our patient and the neuroradiological findings and the favorable clinical outcome still remain unexplained.

  6. EFFICACY OF THE KETOGENIC DIET AS A THERAPY FOR INTRACTABLE EPILEPSY IN CHILDREN

    OpenAIRE

    MIRJAVADI Seyed Alireza; TONEKABONI, Seyed Hassan; GHAZAVI, Mohammadreza; Azargashb, Eznollah; ABDOLLAH GORJI, Fatemeh; Mohammad GHOFRANI

    2010-01-01

    ObjectiveTo determine the role of ketogenic diet in the treatment of intractable epilepsy in children.Materials & MethodsSixty six consecutive children (1-16 years old) with intractable epilepsy whose seizure were not neurodegenerative nor febrile in origin were recruited. They received the ketogenic diet and we evaluated its effect on seizure frequency for 3 months. All these children had more than five seizures per week despite adequate therapy with at least 3-4 anticonvulsant medications. ...

  7. Evaluation of developmental toxicity of guaifenesin using pregnant female rats

    OpenAIRE

    Arham Shabbir; Sadia Shamsi; Muhammad Shahzad; Hajra Ikram Butt; Khurram Aamir; Javed Iqbal

    2016-01-01

    Objectives: Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats. Materials and Methods: Twenty-five dams were divided into five groups. Group 1 served as a control, while Group-2, -3, -4, and -5 were administered with 250, 350, 500, and 600 (mg...

  8. Clonazepam induced maculopapular rash: a case report

    Directory of Open Access Journals (Sweden)

    S. Mabu Shareef

    2013-10-01

    Full Text Available Clonazepam is a benzodiazepine with prominent anticonvulsant action than other members of the group at equisedating doses. It especially blocks pentylenetetrazole-induced seizures. Other important actions include anxiolysis. Common adverse effects to Clonazepam include drowsiness and lethargy. In this submission we report a case of Clonazepam induced maculopapular rash in a 30 year old female treated for panic disorder. [Int J Basic Clin Pharmacol 2013; 2(5.000: 647-649

  9. Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

    OpenAIRE

    Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Charles F. Zorumski

    2010-01-01

    Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectivel...

  10. Differential effects of alprazolam and clonazepam on the immune system and blood vessels of non-stressed and stressed adult male albino rats

    OpenAIRE

    Elmesallamy, Ghada E.; Abass, Marwa A.; Ahmed Refat, Nahla A.G.; Atta, Amal H.

    2011-01-01

    Benzodiazepines belongs to one of the most commonly used anxiolytic and anticonvulsant drugs in the world. Full description of toxic effects on different organs is lacking for nearly all the current benzodiazepines. The aim of the current work was to study the immunologic and vascular changes induced by sub-chronic administration of alprazolam and clonazepam in non-stressed and stressed adult male albino rats. Forty-two adult male albino rats were divided into 6 groups (I): (Ia) Negative cont...

  11. Respiratory and sedative effects of clobazam and clonazepam in volunteers.

    OpenAIRE

    Wildin, J D; Pleuvry, B J; Mawer, G E; Onon, T; Millington, L

    1990-01-01

    1. The respiratory and psychomotor effects of two benzodiazepines used mainly as anticonvulsants were compared in healthy volunteers, using a double-blind placebo controlled design. 2. Clobazam (10 and 20 mg) produced significantly fewer psychomotor side effects than clonazepam (0.5 and 1 mg). Neither drug at either dose affected the ventilatory response to CO2. 3. Although clonazepam produced significant effects on psychomotor performance, these did not correlate with plasma drug concentrati...

  12. Clonazepam induced maculopapular rash: a case report

    OpenAIRE

    S. Mabu Shareef; P. Sai Krishna; Naser A. Tadvi; C. Dinesh M. Naidu

    2013-01-01

    Clonazepam is a benzodiazepine with prominent anticonvulsant action than other members of the group at equisedating doses. It especially blocks pentylenetetrazole-induced seizures. Other important actions include anxiolysis. Common adverse effects to Clonazepam include drowsiness and lethargy. In this submission we report a case of Clonazepam induced maculopapular rash in a 30 year old female treated for panic disorder. [Int J Basic Clin Pharmacol 2013; 2(5.000): 647-649

  13. Ketogenic Diets and Pain

    OpenAIRE

    Masino, Susan A.; Ruskin, David N.

    2013-01-01

    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

  14. Oxcarbazepine: validation and application of an analytical method

    OpenAIRE

    Paula Cristina Rezende Enéas; Renata Barbosa de Oliveira; Gerson Antônio Pianetti

    2010-01-01

    Oxcarbazepine (OXC) is an important anticonvulsant and mood stabilizing drug. A pharmacopoeial monograph for OXC is not yet available and therefore the development and validation of a new analytical method for quantification of this drug is essential. In the present study, a UV spectrophotometric method for the determination of OXC was developed. The various parameters, such as linearity, precision, accuracy and specificity, were studied according to International Conference on Harmonization ...

  15. Epilepsy and marijuana - a review Epilepsia e maconha - uma revisão

    OpenAIRE

    Fábio Galvão Dantas

    2005-01-01

    ABSTRACT The medicinal use of components of Cannabis sativa (marijuana) has been studied around the world. Some of these components may have anti-convulsive properties, though the reports are controversial, and sometimes come from single case reports and clinical anecdotes. Because of ethical aspects, as some of the components of cannabis have psychotropic effects, this is a very important issue. New researches have demonstrated that some components of cannabis that don't have psychotropic ac...

  16. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review

    OpenAIRE

    Khorasany, Alireza Rezaee; Hosseinzadeh, Hossein

    2016-01-01

    Saffron, the dried red-orange stigmas of Crocus sativus L, has been known as a flavoring agent, food coloring and traditional herbal medicine. Pharmacological effects of saffron are mainly attributed to crocin, crocetin, picrocrocin and safranal. These components especially crocin, have significant effects including antidepressant and anticonvulsant, analgesic, anti-cancer and other therapeutic effects on different parts of our body namely cardiovascular, immune, respiratory, genital-urinary ...

  17. Saffron as an antidote or a protective agent against natural or chemical toxicities

    OpenAIRE

    Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2015-01-01

    Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, m...

  18. Seizures and X-linked intellectual disability

    OpenAIRE

    Stevenson, Roger E.; Holden, Kenton R; Rogers, R. Curtis; Schwartz, Charles E

    2012-01-01

    Intellectual disability occurs as an isolated X-linked trait and as a component of recognizable X-linked syndromes in the company of somatic, metabolic, neuromuscular, or behavioral abnormalities. Seizures accompany intellectual disability in almost half of these X-linked disorders. The spectrum of seizures found in the X-linked intellectual disability syndromes is broad, varying in time of onset, type of seizure, and response to anticonvulsant therapy. The majority of the genes associated wi...

  19. Phase II trial of irinotecan and thalidomide in adults with recurrent glioblastoma multiforme

    OpenAIRE

    Puduvalli, Vinay K.; Giglio, Pierre; Groves, Morris D.; Hess, Kenneth R.; Gilbert, Mark R.; Mahankali, Srikanth; Jackson, Edward F.; Levin, Victor A.; Conrad, Charles A.; Hsu, Sigmund H.; Colman, Howard; de Groot, John F.; Ritterhouse, MeLesa G.; Ictech, Sandra E.; Alfred Yung, W. K.

    2008-01-01

    This phase II study aimed at determining the efficacy and safety of irinotecan combined with thalidomide in adults with recurrent glioblastoma multiforme (GBM) not taking enzyme-inducing anticonvulsants (EIACs). Adult patients (⩾18 years) with recurrent GBM with up to three relapses following surgery and radiation therapy were eligible for this trial. The primary end point was rate of progression-free survival at 6 months (PFS-6); secondary end points were response rate, overall survival, and...

  20. Experimental study of neuropharmacological profile of Euphorbia pulcherrima in mice and rats

    Directory of Open Access Journals (Sweden)

    Kundan Kr Singh

    2012-01-01

    Full Text Available Context: Euphorbia pulcherrima (EP belongs to the family: Euphorbiaceae and Genus: Euphorbia. Many species of Euphorbia have been reported as having beneficial properties like anticonvulsive effect, central analgesic properties, antipyretic action, central depressant action and strong sedative effect. However, little study has been done and published on EP. Aims: To observe and evaluate various neuropharmacological effects like antinociceptive effect, anticonvulsant effect, motor in-coordination, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats. Setting and Design: Quantitative experimental study in mice and rats by various experimental models. Materials and Methods: Different experimental models were used to assess the antinociceptive effect (hotplate, tail flick and acetic acid induced writhing test, anticonvulsant effect (Maximal Electroshock Seizure test [MES] and Pentylenetetrazole induced seizures [PTZ], motor in-coordination effect (Rota rod test, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats after oral administration of EP crude dried extracts in three different doses (250, 500 and 1000 mg/kg. Statistical Analysis Used: The significance of difference with respect to control was evaluated using the Mann-Whitney U test. A probability (P-value level less than 0.05 was considered as significant. Results: In MES test model, duration of tonic hind limb extension in mice treated with EP was significantly less as compared to vehicle treated group. EP was most effective in a dose of 1000 mg/kg. There was also significant increase in the latency and decrease in the incidence of convulsions with the use of EP in three different doses in PTZ induced seizure model. Conclusions: This study showed EP (crude dried extracts to possess anticonvulsant properties but no effect on motor co-ordination and anxiety.

  1. Pharmacognostical study on fruit of ziziphus xylopyrus (retz.) Willd

    OpenAIRE

    Singhal U; Goyal A; Solanki N S; Jain V K; Goyal P K

    2012-01-01

    Ziziphus xylopyrus (Retz.) willd known as katber is used traditionally in the treatment of various diseases like Bronchial Asthma, Thirst, Diarrhoea and as Aphrodisiac, Antimicrobial, Antiinflammatory Antinoceceptive and as Anticonvulsants. Present Paper deals with Pharmacognostic study of fruit part of Ziziphus xylopyrus (Retz.) willd.,for its identification and to distinguish it from the coexisting weeds and adulterants. The Secton of fruit has thick pericarp, hard and thick seeds and scler...

  2. Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus

    OpenAIRE

    Rob Mason; Cheer, Joseph F

    2009-01-01

    Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg/kg, i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid a...

  3. Cannabinoid Receptor Activation Reverses Kainate-Induced Synchronized Population Burst Firing in Rat Hippocampus

    OpenAIRE

    Mason, Rob; Cheer, Joseph F

    2009-01-01

    Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg kg−1, i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid a...

  4. Phyto-pharmacology of Celastrus paniculatus: An Overview

    OpenAIRE

    Bhanumathy, M.; S B Chandrasekar; Uma Chandur; Somasundaram, T

    2010-01-01

    Celastrus paniculatus (CP), a traditional Ayurvedic medicinal plant used for centuries as a memory enhancing, anti-inflammatory, analgesic, sedative and antiepileptic agent. The seed extract has been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, anticonvulsant and other pharmacological effects of CP preparations/extra...

  5. Effect of intracerebroventricular injection of COX-1 inhibitor (ketoprofen) on PTZ-induced seizures in male rat

    OpenAIRE

    Elham norouzi; Keyvan Keramati; Morteza Zendehdel

    2010-01-01

    Introduction: Ketoprofen is an NSAID and selective COX-1 inhibitor. In our previous study the role of flunixin meglumine, a nonselective COX inhibitor was studied on seizure and its anticonvulsant effects were confirmed. Therefore this research is performed to assess the role of a selective COX-1 inhibitor, ketoprofen in treatment of seizures induced by PTZ. Methods: In this research, male Wistar rats (200±20 g) were given intracerebroventricular injections (1μl volume in each), of saline or ...

  6. Aqueous stem bark extract of Stereospermum kunthianum (Cham, Sandrine Petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in rodents.

    Science.gov (United States)

    Ching, F P; Omogbai, E K I; Otokiti, I O

    2009-01-01

    Stereospermum kunthianum, Cham Sandrine Petit (Bignoniaceae) known in English as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 - 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 - 400mg/kg, i.p.) remarkably protected (76.9% and 84.6 % respectively) the rats against electroshock-induced seizures. However, the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3% and 55.6% respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg, i.p.) significantly delayed (pmice. Although the findings in the present study do not provide conclusive evidence, it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions. PMID:20606775

  7. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    OpenAIRE

    Krasowski, Matthew D

    2010-01-01

    In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monito...

  8. Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action

    OpenAIRE

    Soares-da-Silva, Patrício; Pires, Nuno; Bonifácio, Maria João; Loureiro, Ana I; Palma, Nuno; Wright, Lyndon C

    2015-01-01

    Eslicarbazepine acetate (ESL) is a once daily antiepileptic drug (AED) approved by the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and Health Canada as an adjunctive therapy in adults with partial-onset seizures (POS). In humans and in relevant animal laboratory species, ESL undergoes extensive first pass hydrolysis to its major active metabolite eslicarbazepine that represents ∼95% of circulating active moieties. ESL and eslicarbazepine showed anticonvulsant activ...

  9. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study

    OpenAIRE

    Jacobson, Mercedes P.; Pazdera, Ladislav; Bhatia, Perminder; Grinnell, Todd; Cheng, Hailong; Blum, David; ,

    2015-01-01

    Background Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. The possible role of ESL as monotherapy to treat POS has not yet been established. Methods This study was an 18-week, multicenter, randomized double-blind trial of gradual conversio...

  10. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models

    OpenAIRE

    Qing, Hong; He, Guiqiong; Ly, Philip T. T.; Fox, Christopher J; Staufenbiel, Matthias; Cai, Fang; Zhang, Zhuohua; Wei, Shengcai; Sun, Xiulian; Chen, Chia-Hsiung; Zhou, Weihui; Wang, Ke; Song, Weihong

    2008-01-01

    Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-secretase cleavage. The molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. Valproic acid (VPA) is one of the most widely used anticonvulsant and mood-stabilizing agents for treating epileps...

  11. CONTEMPORARY APPROACHES TO THE TRIGEMINAL NEURALGIA THERAPEUTIC MANAGEMENT

    OpenAIRE

    Khatuaeva, Aminat; Karpov, Sergey; Frantseva, Anastasia

    2014-01-01

    Trigeminal neuralgia is one of the most widespread cases of prosopalgia characterized by a high intensiveness of pain attacks as well as by an exclusive resistance to different therapeutic methods. [2, 39-41; 3, 326-329]. Specific paroxysmal character of pain attacks in trigeminal neuralgia defines its therapy techniques. The first medication which gave a significant effect in the therapy of trigeminal neuralgia was Dilantin. Blom in 1973 was the first who used anticonvulsants for pain manage...

  12. Pharmacognostical and physicochemical evaluation of Agasti leaf

    OpenAIRE

    Yadav, Pramod; Harisha, C. R.; Prajapati, P. K.

    2010-01-01

    Sesbania grandiflora (L.) Pers., commonly known as Agasti, is widely used in Ayurveda for the treatment of diseases and for processing of various formulations in Rasashastra. It is used for its astringent, antihistaminic, anxiolytic, anticonvulsive and febrifugal activities. Moreover, because of its edible nature, the leaves and pods are used as flavoring items in the cuisine of South India. A detailed investigation of fresh and powder of leaves of Agasti was carried out. The diagnostic chara...

  13. Phenytoin induced life threatening macroglossia in a child

    Directory of Open Access Journals (Sweden)

    Rakesh Mondal

    2013-01-01

    Full Text Available Isolated acquired macroglossia of tongue rarely reported. It occurs due to causes like hereditary angioedema, localized angioedema, etc., Here we describe an 8-year-old boy developing life threatening localized angioedema of tongue due to phenytoin without any association with drug reaction with eosinophilia and systemic symptoms (DRESS syndrome or pseudolymphoma encountered in rural medical college. Anticonvulsants, that is, phenytoin induced this isolated peculiar complication, which was not described before.

  14. Mannich reaction: A versatile and convenient approach to bioactive skeletons

    Indian Academy of Sciences (India)

    Selva Ganesan Subramaniapillai

    2013-05-01

    This review gives an insight into the recent applications of Mannich reaction and its variants in the construction of bioactive molecules. Emphasis is given to the Mannich reaction that provides bioactive molecules and/or modifies the property of an existing bioactive molecule. The role of Mannich reaction in the construction of antimalarial, antitumour, antimicrobial, antitubercular, antiinflammatory and anticonvulsant molecules and also the significance of aminoalkyl Mannich side chain on the biological property of molecules is discussed here.

  15. Stevens–Johnson syndrome induced by a combination of lamotrigine and valproic acid

    OpenAIRE

    Kavitha, S.; Anbuchelvan, T.; Mahalakshmi, V; Sathya, R.; Sabarinath, T. R.; Gururaj, N.; Kalaivani, S.

    2015-01-01

    Lamotrigine and valproic acid are well-tolerated anticonvulsants, but frequently associated with severe cutaneous reactions, such as the Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis, when used in combination. We report a case of SJS likely induced by the use of a lamotrigine and valproic acid regimen and as a dental surgeon it is important to identify such lesion and report to pharmacovigilance.

  16. [3 cases of gingival hyperplasia during nifedipine therapy].

    Science.gov (United States)

    Doria, G; Cangemi, F; Gulizia, M; Lo Giudice, P; Circo, A

    1990-03-01

    The authors report the cases of three male patients, aged 36, 54 and 52 years, who developed gingival hypertrophy during treatment with nifedipine at a dose of 40 mg/daily. Hypertrophy was the same as that observed in patients treated with anti-convulsive or cytostatic drugs, and may probably be due to interference with calcium ions and local factors. Full recovery was achieved by suspending nifedipine treatment in all patients. PMID:2348911

  17. Trimethoprim-sulfamethoxazole induced toxic epidermal necrolysis: a case report

    Directory of Open Access Journals (Sweden)

    Rama R. Bhosale

    2013-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a rare but serious dermatological disorder commonly caused as an idiosyncratic reaction to drugs and the most common drugs implicated are antibiotics, anticonvulsants and non-steroidal anti-inflammatory drugs. Here, we report a case of trimethoprim-sulfamethoxazole induced TEN in a 26 years old female. [Int J Basic Clin Pharmacol 2013; 2(6.000: 841-842

  18. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival

    OpenAIRE

    Jariya Umka Welbat; Apiwat Sirichoat; Wunnee Chaijaroonkhanarak; Parichat Prachaney; Wanassanun Pannangrong; Poungrat Pakdeechote; Bungorn Sripanidkulchai; Peter Wigmore

    2016-01-01

    Valproic acid (VPA) is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC) activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella as...

  19. Ovarian steroids in rat and human brain : effects of different endocrine states

    OpenAIRE

    Bixo, Marie

    1987-01-01

    Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have ...

  20. Tiagabine May Reduce Bruxism and Associated Temporomandibular Joint Pain

    OpenAIRE

    Kast, R. E.

    2005-01-01

    Tiagabine is an anticonvulsant gamma-aminobutyric acid reuptake inhibitor commonly used as an add-on treatment of refractory partial seizures in persons over 12 years old. Four of the 5 cases reported here indicate that tiagabine might also be remarkably effective in suppressing nocturnal bruxism, trismus, and consequent morning pain in the teeth, masticatory musculature, jaw, and temporomandibular joint areas. Tiagabine has a benign adverse-effect profile, is easily tolerated, and retains ef...

  1. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

    Science.gov (United States)

    Shingade, Pravin U; Wankhede, Vaishali; Kataria, Pritam S; Sonone, Nitin

    2014-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides. Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin. PMID:24700960

  2. Pregabalin for the management of fibromyalgia syndrome

    OpenAIRE

    Boomershine, Chad

    2010-01-01

    Chad S BoomershineDepartment of Medicine, Vanderbilt University, Nashville, TN, USAAbstract: This last article in a three-part series on approved medications for managing fibromyalgia syndrome (FMS) reviews pregabalin (Lyrica®). Pregabalin was the first drug approved for FMS management and, as an anticonvulsant, differs from the other approved agents that are antidepressants. Pregabalin inhibits presynaptic excitatory neurotransmitter release by blocking a2d calcium channels....

  3. Nitric oxide (NO) and an NMDA receptor antagonist in pentylenetetrazole-induced convulsions

    OpenAIRE

    Jelenković Ankica V.; Jovanović Marina D.; Ninković Milica; Maksimović Milan; Bošković Bogdan

    2003-01-01

    Controversy about proconvulsant and anticonvulsant nitric oxide (NO) effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) antagonist, in pentylenetetrazole (PTZ)-induced convulsions. Pentylenetetrazole was applied to adult Wistar...

  4. Prevention of disorders of behavioral reactions in rats using nootropics with sodium valproate

    Directory of Open Access Journals (Sweden)

    Ivanov A.V.

    2013-06-01

    Full Text Available Using of anticonvulsants can trigger a number of side effects, such as possible changes in behavior and emotional state of people with epilepsy, risk of unwarranted aggression, nervousness, discoordination, sleepiness, encephalopathies. However, the epilepsy itself as a chronic neurological pathology causes cognitive and "epileptic" deficiency, in patients general retardation, sluggishness of mental activity, decreased cognitive abilities de¬velop. Therefore it is advisable to combine anticonvulsants with nootropics with their ability to protect the brain and increase body's resistance to extreme stress, reduce neurological deficits, restore damaged mnestic and mental functions. The author considered the use of nootropics on the background of anticonvulsant sodium valproate (80 mg/kg. Behavioral reactions of white rats in the test "Open field" and muscle tone of white mice in the test "muscle relaxation" were performed on the day 4 nootropics introduction in 1 hour after a single sodium valproate application. It’s shown experimentally that sodium valproate provided systemic depriming action on orientation and exploratory activity of rats: locomotor activity reduced in the number of squares strolled by 62.8% and in the number of vertical uprights by 80%, the amount of peeping into the burrows decreased by 58.7% as compared with the control. In the test "muscle relaxation" sodium valproate reduced muscle strength of mice by 38.6%. Against the background of anticonvulsant application piracetam (500 mg/kg had no effect on the behavioral responses of rats and muscle tone of mice. Citicoline (500 mg/kg increased locomotor activity in the number of squares crossed by 29.7%, in the number of vertical racks – by 20%, and the endurance of mice by 18.6%. Memantine (10 mg/kg in combination with sodium valproate insignificantly decreased (by 8.4% locomotor activity of rats, but increased exploratory activity by 30.5%; withholding of mice on the wire

  5. [Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam].

    Science.gov (United States)

    Bobkov, Iu G; Morozov, I S; Glozman, O M; Nerobkova, L N; Zhmurenko, L A

    1983-04-01

    The central neurotropic effects of 4-phenylpyracetam, a new phenyl analog of pyracetam, were studied and compared with the effects of pyracetam, morpholene and 4-phenylpyrrolidone. 4-Phenylpyracetam was found to activate the operant behavior more powerfully, to remove psychodepressant effects of diazepam, to inhibit post-rotational nystagmus, and to prevent the development of retrograde amnesia. Unlike pyracetam, 4-phenylpyracetam exhibits a specific anticonvulsant action. When given in high doses, the compound under study produces psychodepressant effects. PMID:6403074

  6. Acute and long-term treatment of mania

    OpenAIRE

    Vieta, Eduard; Sanchez-Moreno, Jose

    2008-01-01

    The treatment of mania starts with a correct diagnosis and elementary measures to prevent risks for the patient, relatives, and others. Sometimes, compulsory admission and treatment may be required for a few days. Patients with psychotic or mixed mania may be more difficult to treat. At the present time, there is solid evidence supporting the use of lithium, the anticonvulsants valproate and carbamazepine, and the antipsychotics chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine...

  7. The Role of Flavonoids on Oxidative Stress in Epilepsy

    OpenAIRE

    2015-01-01

    Backgrounds. Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. Objective. This review provides an overview about the role of flavonoids in oxidative stress in epil...

  8. Derivatives of valproic acid are active against pentetrazol-induced seizures in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Kubová, Hana; Hen, N.; Yagen, B.; Bialer, M.

    2013-01-01

    Roč. 106, 1-2 (2013), s. 64-73. ISSN 0920-1211 R&D Projects: GA ČR(CZ) GAP304/10/1274; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : experimental seizures * anticonvulsant action * derivatives of valproic acid * immature rats Subject RIV: FH - Neurology Impact factor: 2.190, year: 2013

  9. Silk Fibroin Encapsulated Powder Reservoirs for Sustained Release of Adenosine

    OpenAIRE

    Pritchard, Eleanor M.; Szybala, Cory; Boison, Detlev; Kaplan, David L.

    2010-01-01

    Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the...

  10. Evaluation of central nervous system effects of Citrus limon essential oil in mice

    Directory of Open Access Journals (Sweden)

    Lidianne Mayra Lopes Campêlo

    2011-08-01

    Full Text Available The central nervous system (CNS depressant and anticonvulsant activities of Citrus limon (L. Osbeck, Rutaceae, essential oil (EO were investigated in animal models. The EO (50, 100 and 150 mg/kg injected by oral route (p.o. in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to thirty days after the administration and the dose of 150 mg/kg significantly reduced the remaining time of the animals on the Rota-rod apparatus. Additionally, C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ. The administration of FLU (10 mg/kg, i.p., GABA A-benzodiazepine (GABA-BZD receptor antagonist, antagonized the effect of C. limon essential oil at higher dose. This C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC at higher dose. In the same way, the anticonvulsant effect of the EO was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities in mice that needs further investigation.

  11. Support vector machines using EEG features of cross-frequency coupling can predict treatment outcome in Mecp2-deficient mice.

    Science.gov (United States)

    Colic, Sinisa; Wither, Robert G; Min Lang; Zhang Liang; Eubanks, James H; Bardakjian, Berj L

    2015-08-01

    Anti-convulsive drug treatments of epilepsy typically produce varied outcomes from one patient to the next, often necessitating patients to go through several anticonvulsive drug trials until an appropriate treatment is found. The focus of this study is to predict treatment outcome using a priori electroencephalogram (EEG) features for a rare genetic model of epilepsy seen in patients with Rett Syndrome. Previous work on Mecp2-deficient mice, exhibiting the symptoms of Rett syndrome, have revealed EEG-based biomarkers that track the pathology well. Specifically the presence of cross-frequency coupling of the delta-like (3-6 Hz) frequency range phase with the fast ripple (400 - 600 Hz) frequency range amplitude in long duration discharges was found to track seizure pathology. Support Vector Machines (SVM) were trained with features generated from phase-amplitude comodulograms and tested on (n=6) Mecp2-deficient mice to predict treatment outcome to Midazolam, a commonly used anti-convulsive drug. Using SVMs it was shown that it is possible to generate a likelihood score to predict treatment outcomes on all of the animal subjects. Identifying the most appropriate treatment a priori would potentially lead to improved treatment outcomes. PMID:26737563

  12. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Hsin-Cheng Hsu

    2013-01-01

    Full Text Available Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA, which causes intracellular mitogen-activated protein kinase (MAPK signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR and rhynchophylline (RP have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p. to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg, RP (0.25 mg/kg, and valproic acid (VA, 250 mg/kg for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  13. Cutaneous adverse drug reactions: clinical pattern and causative agents--a 6 year series from Chandigarh, India.

    Directory of Open Access Journals (Sweden)

    Sharma V

    2001-04-01

    Full Text Available AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR and to determine the causative drugs. MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study. The most common types of cutaneous ADR patterns were maculopapular rash (34.6%, fixed drug eruption (FDE (30% and urticaria (14%. The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%, anticonvulsants (22.2% and NSAIDs (18%. Anticonvulsants were implicated in 41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3% and penicillins(20%. Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations. Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.

  14. Natural approaches to epilepsy.

    Science.gov (United States)

    Gaby, Alan R

    2007-03-01

    This article reviews research on the use of diet, nutritional supplements, and hormones in the treatment of epilepsy. Potentially beneficial dietary interventions include identifying and treating blood glucose dysregulation, identifying and avoiding allergenic foods, and avoiding suspected triggering agents such as alcohol, aspartame, and monosodium glutamate. The ketogenic diet may be considered for severe, treatment-resistant cases. The Atkins diet (very low in carbohydrates) is a less restrictive type of ketogenic diet that may be effective in some cases. Nutrients that may reduce seizure frequency include vitamin B6, magnesium, vitamin E, manganese, taurine, dimethylglycine, and omega-3 fatty acids. Administration of thiamine may improve cognitive function in patients with epilepsy. Supplementation with folic acid, vitamin B6, biotin, vitamin D, and L-carnitine may be needed to prevent or treat deficiencies resulting from the use of anticonvulsant drugs. Vitamin K1 has been recommended near the end of pregnancy for women taking anticonvulsants. Melatonin may reduce seizure frequency in some cases, and progesterone may be useful for women with cyclic exacerbations of seizures. In most cases, nutritional therapy is not a substitute for anticonvulsant medications. However, in selected cases, depending on the effectiveness of the interventions, dosage reductions or discontinuation of medications may be possible. PMID:17397265

  15. Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures

    International Nuclear Information System (INIS)

    L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific 3H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of 3H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor

  16. Analysis of β-Subunit-dependent GABAA Receptor Modulation and Behavioral Effects of Valerenic Acid Derivatives.

    Science.gov (United States)

    Khom, S; Hintersteiner, J; Luger, D; Haider, M; Pototschnig, G; Mihovilovic, M D; Schwarzer, C; Hering, S

    2016-06-01

    Valerenic acid (VA)-a β2/3-selective GABA type A (GABAA) receptor modulator-displays anxiolytic and anticonvulsive effects in mice devoid of sedation, making VA an interesting drug candidate. Here we analyzed β-subunit-dependent enhancement of GABA-induced chloride currents (IGABA) by a library of VA derivatives and studied their effects on pentylenetetrazole (PTZ)-induced seizure threshold and locomotion. Compound-induced IGABA enhancement was determined in oocytes expressing α1β1γ2S, α1β2γ2S, or α1β3γ2S receptors. Effects on seizure threshold and locomotion were studied using C57BL/6N mice and compared with saline-treated controls. β2/3-selective VA derivatives such as VA-amide (VA-A) modulating α1β3γ2S (VA-A: Emax = 972 ± 69%, n = 6, P tetrazole (α1β3γ2S: VA-TET: EC50 = 6.0 ± 1.0 μM, P < 0.05; VA-TET: 0.3 mg/kg: 47.3 ± 0.5 mg/kg PTZ versus VA: 10 mg/kg: 49.0 ± 1.8 mg/kg PTZ, P < 0.05). At higher doses (≥10 mg/kg), VA-A, VA-MA, and VA-TET reduced locomotion. In contrast, unselective VA derivatives induced anticonvulsive effects only at high doses (30 mg/kg) or did not display any behavioral effects. Our data indicate that the β2/3-selective compounds VA-A, VA-MA, and VA-TET induce anticonvulsive effects at low doses (≤10 mg/kg), whereas impairment of locomotion was observed at doses ≥10 mg/kg. PMID:27190170

  17. Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats

    Institute of Scientific and Technical Information of China (English)

    Qing LI; Chun-lei JIN; Li-sha XU; Zheng-bin ZHU-GE; Li-xia YANG; Lu-ying LIU; Zhong CHEN

    2005-01-01

    Aim: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. Methods:Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and γ-aminobutyric acid levels were measured by high performance liquid chromatography (HPLC). Results: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no meliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. Conclusion: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.

  18. Use of select medications prior to duloxetine initiation among commercially-insured patients

    Directory of Open Access Journals (Sweden)

    Bernauer M

    2012-08-01

    Full Text Available Mark Bernauer,1 Ning Wu,2 Shih-Yin Chen,2 Xiaomei Peng,1 Luke Boulanger,2 Yang Zhao11Eli Lilly and Company, Indianapolis, IN, 2United BioSource Corporation, Lexington, MA, USABackground: The purpose of this study was to assess select medication utilization prior to duloxetine initiation among patients with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain associated with osteoarthritis or low back pain.Methods: Commercially insured duloxetine initiators between January 1, 2007 and March 31, 2010 were identified from a large US administrative claims database. Disease subgroups were constructed based on diagnosis from medical claims during the 12 months prior to duloxetine initiation. Prior use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, and muscle relaxants was assessed during the 12-month preinitiation period.Results: This study identified 56,845 (2007, 44,838 (2008, and 65,840 (January 2009 to March 2010 duloxetine initiators. Among the 2009 initiators, utilization patterns were similar for patients with major depressive disorder and generalized anxiety disorder, with antidepressants being the most used (84% and 80%, respectively, followed by opioids (58% and 55%, respectively. Patients across pain-related conditions also had similar utilization patterns, with opioid use being the highest (76%–82%, followed by antidepressants (65%–72%. Use of other medication classes was common (29%–63% but less frequent, and over 50% of the patients used any antidepressants, 70% used any antidepressants or anticonvulsants, and 90% used any antidepressants, anticonvulsants, or opioids. Trends in the use of these select medications were similar between 2007 and 2009.Conclusion: Patients used several types of medications over the 12 months prior to initiating duloxetine across disease states, with antidepressants and opioids being the

  19. Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

    Science.gov (United States)

    Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y

    2005-08-01

    Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211

  20. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models

    Science.gov (United States)

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias

    2016-01-01

    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID:27281030

  1. Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity

    Directory of Open Access Journals (Sweden)

    K. N. Venugopala

    2013-01-01

    Full Text Available Coumarin (2H-1-benzopyran-2-one is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further.

  2. Febrile convulsion--a clinical survey and a review of its current concept of management.

    Science.gov (United States)

    Saw, A H; Ho, L; Lim, K W; Cheng, H K

    1989-01-01

    Between February 1986 to November 1986, 335 cases of febrile convulsion were admitted to the paediatric ward, Tan Tock Seng Hospital. The study revealed 87 cases (26%) were complex febrile convulsion and 73 cases (21.8%) were recurrent febrile convulsion. 51 patients with complex febrile convulsion and 32 patients with recurrent febrile seizures were put on long term phenobarbitone. The number of patients with recurrent and complex convulsion was big. The role of anticonvulsant prophylaxis is reviewed and its efficacy discussed. PMID:2638720

  3. Progress in the research of restless legs syndrome

    Directory of Open Access Journals (Sweden)

    WU Wei

    2013-05-01

    Full Text Available Restless legs syndrome (RLS is a neurological disorder characterized by an irresistible urge to move the legs especially at rest. Symptoms worsen in the evening and night and improve with activity such as walking. RLS may be secondary to, or exacerbated by, a number of conditions that include iron deficiency, pregnancy, end stage renal disease, diabetes and rheumatoid arthritis, or with neurological disorders such as peripheral neuropathy. Treatments for RLS include: dopaminergic agents, dopamine receptor agonists, opioids, sedative hypnotics, anticonvulsants, clonidine, minerals and vitamins et al.

  4. Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard;

    2013-01-01

    β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

  5. MODIFIED ATKINS DIET FOR INTRACTABLE CHILDHOOD EPILEPSY

    OpenAIRE

    Mohammad BARZEGAR; Poupak IRANDOUST; Ebrahimi Mameghani, Mehrangiz

    2010-01-01

    ObjectiveThe aim of the present study was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy.Materials & MethodsTwenty one children with medically intractable epilepsy were enrolled in the study. Inclusion criteria were at least four seizures per month and a trial of at least three anticonvulsants without becoming seizure-free. The subjects received the diet over a 6-month period.ResultsThree months after diet initiation, 15 patients (71.4%)...

  6. Perinatal Influences of Valproate on Brain and Behaviour: An Animal Model for Autism.

    Science.gov (United States)

    Ranger, Peter; Ellenbroek, Bart A

    2016-01-01

    Valproic acid or valproate (VPA) is an anti-convulsant and mood stabiliser effective in treating epilepsy and bipolar disorders. Although in adults VPA is well tolerated and safe, there is convincing evidence that it has teratogenic properties, ranging from mild neurodevelopmental changes to severe congenital malformations. In particular, studies involving humans and other animals have shown that prenatal exposure to VPA can induce developmental abnormalities reminiscent of autism spectrum disorder (ASD). In this chapter, we discuss the connection between VPA and ASD, evaluate the VPA animal model of ASD, and describe the possible molecular mechanisms underlying VPA's teratogenic properties. PMID:26510739

  7. Microsomal metabolism of erythraline: an anxiolitic spiroalkaloid

    Directory of Open Access Journals (Sweden)

    Lucas Maciel Mauriz Marques

    2015-10-01

    Full Text Available ABSTRACTThe genus Erythrina, Fabaceae, is widely distributed in tropical and subtropical regions. Their flowers, fruits, seeds and bark are frequently used in folk medicine for its effects on the central nervous system such as anticonvulsant, antidepressant, analgesic, sedative, and hypnotic effects. Erythraline has been reported as one of the active compounds from Erythrina, but until now there are no pharmacokinetics data about this compound and only few results showing a putative metabolism were reported. To improve the information about erythraline metabolism, this article reports and discusses, for the first time, the in vitrometabolism biotransformation of erythraline by cytochrome P450 enzymes.

  8. Efficacy of concomitant use of dexmedetomidine and propofol in tetanus.

    Science.gov (United States)

    Miya, Ken; Shimojo, Nobutake; Koyama, Yasuaki; Enomoto, Yuki; Hagiya, Keiichi; Yamasaki, Yuichiro; Nishino, Tomofumi; Kawano, Satoru; Mizutani, Taro

    2015-12-01

    Tetanus is an infectious disease caused by Clostridium tetani, which manifests systemic convulsion and autonomic instability associated with high case fatality. Despite proper medical intervention, management of those symptoms is often difficult. We report a case of 67-year-old man with tetanus in which a concomitant use of dexmedetomidine, an adrenaline α-2 receptor agonist, and propofol, a GABA(A) receptor binding agent, was successful in the management of systemic convulsion and autonomic instability without necessitating conventional anticonvulsant, neuromuscular blocking agents, or tracheostomy. PMID:25989896

  9. Structure-activity relationships in cinnamamides. 1. Synthesis and pharmacological evaluation of some (E)- and (Z)-N-alkyl-alpha,beta-dimethylcinnamamides.

    Science.gov (United States)

    Balsamo, A; Barili, P L; Crotti, P; Macchia, D; Macchia, F; Pecchia, A; Cuttica, A; Passerini, N

    1975-08-01

    Two series of (E)- and (Z)-N-alkyl-alpha,beta-dimethylcinnamamide derivatives were prepared and the biological activity of these compounds was investigated in a series of pharmacological tests. All compounds tested had clear activity on the CNS; generally, this was depressant with E isomers, while Z isomers always caused marked stimulation (tremors and convulsions). Some of the E isomers also had a clear-cut anticonvulsant activity as shown by the antagonistic effect on pentylenetetrazole-induced seizures in the mouse. The NMR spectra of these compounds, which confirm their configurations, are discussed. PMID:1159703

  10. Driving and Epilepsy: a Review of Important Issues.

    Science.gov (United States)

    Kang, Joon Y; Mintzer, Scott

    2016-09-01

    Driving restrictions in people with epilepsy (PWE) is a highly contentious topic. The fundamental difficulty lies in achieving a balance between safety and practicality. The aim of this review is to provide an overview, history, and rationale behind current laws regarding driving restriction in PWE. We also discuss recent findings that may be helpful to practitioners during individual discussions with PWE including seizure recurrence risk after first seizure, recurrent seizure, and anticonvulsant with drawl and driving restrictions in patients with psychogenic non-epileptic seizures (PNES). PMID:27443647

  11. An updated review on the parasitic herb of Cuscuta reflexa Roxb.

    Directory of Open Access Journals (Sweden)

    Satish Patel

    2012-03-01

    Full Text Available ABSTRACT: Cuscuta reflexa Roxb. is a golden yellow, leafless, perennial, parasitic herb of the family Convolvulaceae. C. reflexa has been investigated for antispasmodic, hemodynamic, anticonvulsant, antisteroidogenic, antihypertensive, muscle relaxant, cardiotonic, antiviral, antibacterial, antioxidant, cholinergic, diuretic and hair growth activities. Many chemical constituents have been isolated from C. reflexa such as cuscutin, amarbelin, β-sitosterol, stigmasterol, kaempferol, dulcitol, myricetin, quercetin, coumarin and oleanolic acid. This review presents a detailed survey of the literature on pharmacognosy, phytochemistry and traditional and biological medicinal uses of C. reflexa.

  12. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS).

    Science.gov (United States)

    Gill, Shaman; Sagar, Amitabh; Shankar, S; Nair, Velu

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids. PMID:24014920

  13. Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders

    International Nuclear Information System (INIS)

    Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane. Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative, hypnosis, anticonvulsion and anxiolysis. PET can be utilized to study the binding of the receptors in vivo. PET radioligands of gamma-aminobutyric acid type A-benzodiazepine receptors can be classified into 3 types: antagonists,agonists and reverse agonists, of which antagonist radiotracer 11C-flumazenil is the most commonly applied in epilepsy, anxiety disorders, depression, vegetative state,addiction and other neuro-psychiatric disorders. (authors)

  14. Status epilepticus in scleromyxedema

    Institute of Scientific and Technical Information of China (English)

    Soifa Markoula; Soifa Zouroudi; Soitrios Giannopoulos; Kimon Tsoukanelis; Ananstasia Zikou; Athanassios P Kyritsis

    2016-01-01

    Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yelowish lichenoid waxy papules. Neurological manifestations are rare but wel-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradualy recovered fuly. A complete remission of the lesions was shown in a folow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especialy when combined with brain MRI lesions, and treat the patient appropriately.

  15. Simultaneous occurrence of toxic epidermal necrolysis and neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Muhammed K

    2005-01-01

    Full Text Available Toxic epidermal necrolysis (TEN is an acute life-threatening blistering disease characterized by involvement of the skin, multiple mucous membranes and internal organs. It is most commonly precipitated by the administration of medications like anticonvulsants. Neuroleptic malignant syndrome (NMS is a rare complication of neuroleptic therapy characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction. An 18-year-old girl presenting with simultaneous appearance of TEN and NMS following anti-psychotic drugs given for bipolar mood disorder, is reported for the rare association and her complete recovery.

  16. Critical evaluation of P2X7 receptor antagonists in selected seizure models

    OpenAIRE

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A; Henshall, David C.; Engel, Tobias

    2016-01-01

    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable ...

  17. Acute hemolysis in a patient with a newly diagnosed glioblastoma.

    Science.gov (United States)

    Murphy, Adrian G; Grossman, Stuart A

    2016-07-01

    We describe a 62-year-old of Egyptian origin who presented with sudden, severe and symptomatic anemia requiring hospitalization shortly after beginning concurrent radiation and temozolomide for his newly diagnosed glioblastoma. He had also recently been started on steroids, anticonvulsants and Pneumocystis jirovecii prophylaxis. He was ultimately diagnosed with G6PD deficiency with an acute hemolytic anemia precipitated by dapsone. Screening for G6PD deficiency should be considered in high-risk patient populations where P. jirovecii prophylaxis is planned. PMID:27230975

  18. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model

    OpenAIRE

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Kondrat-Wrobel, Maria W.; Tutka, Piotr; Jarogniew J Luszczki

    2014-01-01

    The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were...

  19. [Chemotherapy induced peripheral neuropathy].

    Science.gov (United States)

    Kolak, Agnieszka; Starosławska, Elzbieta; Kubiatowski, Tomasz; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Mocarska, Agnieszka; Burdan, Franciszek

    2013-11-01

    Modern cancer therapy prolongs patients life but commonly increases incidence of treatment-related complications. One of such adverse effect is a neurotoxicity, which usually manifestates as peripheral neuropathies (CIPN), characterised by various sensory (tingling, numbness, pain), motor (foot and hands drop, fastening buttons difficulties) and autonomic (constipation, arythmia) abnormalities as well as pain. Despite of intensive epidemiological and clinical studies, standardized diagnostic criteria and methods of the neuropathy prevention and treatment have not been fully established. The most commonly used form of treatment is symptomatic therapy, including anticonvulsant and antidepressant drugs. Proper education of patients and their families of symptoms and neuropathy consequences is desirable to reduce anxiety and stress. PMID:24575651

  20. Drug: D00280 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00280 Drug Clonazepam (JP16/USP/INN); Klonopin (TN) C15H10ClN3O3 315.0411 315.7112...gents affecting central nervous system 113 Antiepileptics 1139 Others D00280 Clonazepam (JP16/USP/INN) Anato... ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AE Benzodiazepine derivatives N03AE01 Clonazepam D00280 Clonazepam (J...P16/USP/INN) USP drug classification [BR:br08302] Anticonvulsants Gamma-aminobutyric Acid (GABA) Augmenting Agents Clonazepam... D00280 Clonazepam (JP16/USP/INN) Anxiolytics Benzodiazepines Clonazepam D00280 Clonazepam

  1. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS

    Directory of Open Access Journals (Sweden)

    Shaman Gill

    2013-01-01

    Full Text Available Drug rash with eosinophilia and systemic symptoms (DRESS syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids.

  2. Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

    International Nuclear Information System (INIS)

    Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated 36Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced by them

  3. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine; Pedersen, J L; Kehlet, H

    2001-01-01

    BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1...... stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). RESULTS: The burn injury induced significant primary and secondary hyperalgesia...... inflammation following a thermal injury. These observations suggest a clinical potential of gabapentin in the treatment of postoperative pain....

  4. Management of neuropathic pain following treatment for breast cancer in the absence of recurrence: a challenge for the radiation oncologist

    International Nuclear Information System (INIS)

    This report reviews various management options for treatment-induced neuropathic pain in breast cancer. First-line options include tricyclic antidepressants and anticonvulsant drugs. Opioids should be prescribed according to published guidelines. Second-line treatments include lignocaine, mexiletine and ketamine. Sympatholytic therapies are available to patients with features of chronic regional pain syndrome. Anti-inflammatory agents are used for neurogenic inflammation. Surgical interventions are considered for refractory neuropathic pain. Interdisciplinary management is appropriate when persisting pain causes physical and psychosocial disabilities. Copyright (2004) Blackwell Science Pty Ltd

  5. Therapeutic management of locally unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10 % of patients can undergo surgery with an overall 5-year survival rate of less than 2 %. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used. (author)

  6. Inhibition of delayed rectifier K+ channels by phenytoin in rat neuroblastoma cells

    OpenAIRE

    Nobile, Mario; Vercellino, Paolo

    1997-01-01

    The action of the anticonvulsant drug phenytoin on K+ currents was investigated in neuroblastoma cells by whole-cell voltage-clamp recording.Neuroblastoma cells expressed an outward K+ current with a voltage- and time-dependence which resembled the delayed-rectifier K+ current found in other cells. When added to the standard external solution at concentrations ranging between 1 and 200 μM, phenytoin reduced the current (n=65). Inhibition was concentration-dependent with a half-maximal inhibit...

  7. A Steered Molecular Dynamics Study of Binding and Translocation Processes in the GABA Transporter

    DEFF Research Database (Denmark)

    Skovstrup, Soren; David, Laurent; Taboureau, Olivier;

    2012-01-01

    The entire substrate translocation pathway in the human GABA transporter (GAT-1) was explored for the endogenous substrate GABA and the anti-convulsive drug tiagabine. Following a steered molecular dynamics (SMD) approach, in which a harmonic restraining potential is applied to the ligand...... residues in the extracellular vestibule including two lysines (K76 (TM1) and K448 (TM10)) and a TM6-triad (D281, E283, and D287) in attracting and relocating substrates towards the secondary/interim substrate-binding site (S2). Likewise, E101 is highlighted as essential for the relocation of the substrate...

  8. Chronic administration of citalopram inhibited El mouse convulsions and decreased monoamine oxidase-A activity.

    OpenAIRE

    Kabuto, Hideaki; Yokoi, Isao; Endo, Atsushi; Takei, Mineo; Kurimoto, Tadashi; Mori, Akitane

    1994-01-01

    Serotonin (5-HT) is thought to play an important role in the seizures of El mice because the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by chronic administration of citalopram (80 mg/kg/day, p.o. for 2 weeks), but were not inhibited by acute administration of citalopram (80 mg/...

  9. PHYTO-PHARMACOLOGICAL REVIEW OF ARGYREIA NERVOSA

    Directory of Open Access Journals (Sweden)

    A. Krishnaveni

    2011-02-01

    Full Text Available Herbal medicines are the significant and reliable sources for treating various diseases. Argyreia nervosa is traditionally used in wound healing, syphilius,diuretics,rheumatic affections, leucohorrhoea.,cerebral disorders, ulcers, as anti-tumour and to prevent contraception.Phytoconstituents such as flavanoids, steroids, ergoline alkaloids and triterpenoids were identified. Pharmacological studies proved its anticonvulsant, immunomodulatory, hypotensive, anti- inflammatory and nootropic effect.The present form of article highlights the phytochemical and pharmacological studies including traditional practice of Argyreia nervosa have been carried out so far.

  10. Argyreia speciosa (Linn. f. sweet: A comprehensive review

    Directory of Open Access Journals (Sweden)

    V J Galani

    2010-01-01

    Full Text Available Argyreia speciosa (Linn. f. Sweet is a popular Indian medicinal plant, which has long been used in traditional Ayurvedic Indian medicine for various diseases. This plant is pharmacologically studied for nootropic, aphrodisiac, immunomodulatory, hepatoprotective, antioxidant, antiinflammatory, antihyperglycemic, antidiarrheal, antimicrobial, antiviral, nematicidal, antiulcer, anticonvulsant, analgesic and central nervous depressant activities. A wide range of phytochemical constituents have been isolated from this plant. A comprehensive account of the morphology, phytochemical constituents and pharmacological activities reported are included in view of the many recent findings of importance on this plant.

  11. The effect of extracts of Searsia species on epileptiform activity in slices of the mouse cerebral cortex

    DEFF Research Database (Denmark)

    Pedersen, Mikael Egebjerg; Vestergaard, Henrik Tang; Stafford, Gary Ivan; van Staden, Johannes; Jäger, Anna Katharina

    2008-01-01

    ETHNOPHARMACOLOGICAL RELEVANCE: Searsia dentata and Searsia pyroides are used in traditional South African medicine to treat convulsions and epilepsy. Previous studies have demonstrated that extracts of these plants comprise compounds that bind to the flumazenil-sensitive site on the GABA......(A) receptor. However, their use as anticonvulsant medicinal plants cannot be adequately explained by these findings. AIMS: The aim of this study was to examine the possible involvement of the glutamatergic system of extracts from the plants. MATERIALS AND METHODS: The mouse cortical wedge preparation was used...... effect of the crude ethanolic extracts of these two South African medicinal plants was demonstrated....

  12. Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures.

    Science.gov (United States)

    da Silva, Ana Paula dos S C L; Lopes, Joselma S L; Vieira, Priscila de S; Pinheiro, Emanuelly E A; da Silva, Mirna L de G; Silva Filho, José Carlos C L; da Costa, Joaquim S; David, Jorge M; de Freitas, Rivelilson M

    2014-09-01

    Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases in both humans and animals as well as the seed decoction has been used to treat diarrheas and inflammatory diseases. However, there is no research on GFC effects in the central nervous system of rodents. The present study aimed to evaluate the GFC effects at doses of 25, 50 or 75 mg/kg on seizure parameters to determine their anticonvulsant activity and its effects on amino acid (γ-aminobutyric acid (GABA), glutamine, aspartate and glutathione) levels as well as on acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC produced an increased latency to first seizure, at doses 25mg/kg (20.12 ± 2.20 min), 50mg/kg (20.95 ± 2.21 min) or 75 mg/kg (23.43 ± 1.99 min) when compared with seized mice. In addition, GABA content of mice hippocampus treated with GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55% and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed an increase in AChE activity (63.30%) when compared with seized mice. The results indicate that GFC can exert anticonvulsant activity and reduce the frequency of installation of pilocarpine-induced status epilepticus, as demonstrated by increase in latency to first seizure and decrease in mortality rate of animals. In conclusion, our data suggest that GFC may influence in epileptogenesis and promote anticonvulsant actions in pilocarpine model by modulating the GABA and glutamate contents and of AChE activity in seized mice hippocampus. This compound may be useful to produce neuronal protection and it can be considered as an anticonvulsant agent. PMID:24911645

  13. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie;

    2012-01-01

    reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive...... action in animal models of epilepsy. In our study, the anticonvulsant effect of the AEDs was investigated in vivo using several observational parameters (i.e., incidence and duration of convulsions, latency to clonic convulsions, and severity of convulsions). We found that including the observational...

  14. Antidepressant-like effects and mechanisms of flavonoids and related analogues.

    Science.gov (United States)

    Guan, Li-Ping; Liu, Bing-Yu

    2016-10-01

    Flavonoids, possessing a basic phenylbenzopyrone core, are important components of the human diet, and are found in many medicinal plants. Flavonoids include chalcones, flavanones and their derivatives. Synthetic and natural isolated flavonoids display an enormous number of biological activities such as antitumor, antiplatelet, anti-malarial, anti-inflammatory, antidepressant and anticonvulsant properties. This review article focuses on the antidepressant-like effect, structure-activity relationship and mechanism of action of total flavonoid extracts isolation from natural sources, flavonoid compounds and their related analogues. PMID:27214511

  15. Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

    Science.gov (United States)

    Findling, Robert L

    2016-01-01

    Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. PMID:27570928

  16. Evaluation of central nervous system effects of Citrus limon essential oil in mice

    OpenAIRE

    Lidianne Mayra Lopes Campêlo; Sidney Gonçalo Lima; Chistiane Mendes Feitosa; Rivelilson Mendes de Freitas

    2011-01-01

    The central nervous system (CNS) depressant and anticonvulsant activities of Citrus limon (L.) Osbeck, Rutaceae, essential oil (EO) were investigated in animal models. The EO (50, 100 and 150 mg/kg) injected by oral route (p.o.) in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to thirty days after the administration and the dose of 150 mg/kg significantly reduced the remaining time of the animals on the Rota-rod apparatus. Additio...

  17. Resistant Convulsion Due to Emergent Hipocalsemia Dependent Upon Antiepileptic Treatment

    OpenAIRE

    Oğuztürk, Hakan; Turtay, Muhammet Gökhan; Kablan, Yüksel

    2010-01-01

    A case of resistant convulsion led by hypocalcemia in association with long-term treatment with antiepileptic drugs has been reported. A 37-year-old, mentally retarded woman was presented with a 12-month history of loss of seizure control, after being seizure-free for 4 years on a fixed regimen of oxcarbazepine, sodium valproate and phenytoin. She had been institutionalized at the age of 7 years and had received anticonvulsant drugs since she was diagnosed with tonic-clonic epilepsy 30 y...

  18. Toxic Epidermal Necrolysis induced by rarely implicated drugs

    Directory of Open Access Journals (Sweden)

    Sujit Rajagopalan

    2012-01-01

    Full Text Available Toxic Epidermal Necrolysis (TEN and Steven-Johnson Syndrome (SJS are serious disorders commonly caused as idiosyncratic reactions to drugs, the most common ones being oxicams, anticonvulsants, allopurinol, and sulfonamides. We present a case of TEN in a patient who developed the lesions after ingesting multiple drugs including paracetamol, metoclopramide, antihistamines, and multivitamins. These drugs have rarely been implicated in this disorder. The suspected drugs in this case were paracetamol and metoclopramide. However, the role of other drugs could not be ruled out definitely. The patient was managed with antibiotics, corticosteroids, and parenteral fluids and recovered well.

  19. DIVERSE PHARMACOLOGICAL ACTIVITIES OF 3-SUBSTITUTED COUMARINS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Batra Nikhil

    2012-07-01

    Full Text Available Coumarins belong to the family of lactones having benzopyrone system that can be isolated from plants as well as total synthesis can be carried out in the laboratory. To date, many chemical reactions have been established that can be used to synthesize coumarins like Knoevenagel condensation, Perkin, Pechmann, Reformatsky and Wittig reactions. Coumarins have attracted considerable attention of medicinal chemists and pharmacologists in recent years as they have been demonstrated to bear many pharmacological activities like anti-inflammatory & analgesic, antimicrobial, antioxidant, anticancer, analgesic & ulcerogenic, anticonvulsant, antihyperlipidemic, tyrosinase inhibitor and anti-parkinsonism activity. The aim of the present paper is to review the available information on 3-substituted coumarins.

  20. Medicaid's expenditures for newer pharmacotherapies for adults with disabilities.

    Science.gov (United States)

    Shireman, Theresa I; Hall, Jean P; Rigler, Sally K; Moore, Janice M

    2007-01-01

    Medicaid's drug expenditures have grown at double-digit inflation rates since 2000. These prescription drug costs are important contributors to increasing health care costs for disabled persons. In spite of this knowledge, little has been reported about specific patterns of medication use among disabled enrollees. We analyzed Kansas Medicaid data to describe trends in medication use patterns across 3 years among disabled beneficiaries. The marked shifts toward newer medications and disproportionate contributions of newer, more expensive medications to overall prescription costs for antipsychotics, antidepressants, anticonvulsants, antiulcer medications, anti-inflammatory agents, and opioids have implications for both policy and practice. PMID:17722749

  1. Drug: D05775 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05775 Drug Rufinamide (JAN/USAN/INN); Banzel (TN) C10H8F2N4O 238.0666 238.1935 D05775... Agents affecting central nervous system 113 Antiepileptics 1139 Others D05775 Ru...03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AF Carboxamide derivatives N03AF03 Rufinamide D05775 Rufinamide (JA...N/USAN/INN) USP drug classification [BR:br08302] Anticonvulsants Sodium Channel Agents Rufinamide D05775... Rufinamide (JAN/USAN/INN) CAS: 106308-44-5 PubChem: 47207436 LigandBox: D05775 NIKKA

  2. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

    Directory of Open Access Journals (Sweden)

    Pravin U Shingade

    2014-01-01

    Full Text Available Acute generalized exanthematous pustulosis (AGEP is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides.Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin.

  3. 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...... potential and suppressing depolarizing surges. However, Kv7 channels are not expressed exclusively in neurones and data generated over the last decade have shown that Kv7 channels play a key role in various smooth muscle systems of the body. This review discusses the potential of targeting Kv7 channels in...

  4. Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice

    OpenAIRE

    Karadag C.H.; Dokmeci D.; Dost T.; Ulugol A.; Dokmeci I.

    2000-01-01

    We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4,...

  5. What psychotherapists should know about pharmacotherapies for bipolar disorder.

    Science.gov (United States)

    Goldberg, Joseph F

    2007-05-01

    This article provides a practice-friendly overview of current psychotropic agents used for the treatment of bipolar disorder. The author reviews definitions and concepts about mood stabilization according to the evidence base, in turn profiling a "clinical niche" for lithium, anticonvulsant drugs, atypical antipsychotics, and antidepressants. Results from randomized clinical trials are summarized to help clinicians individualize treatment decisions and tailor them to real-world patients. Recognition and management of common adverse effects are discussed alongside risk-benefit strategies to guide optimal treatment that balances clinical efficacy with drug safety and tolerability. PMID:17417812

  6. Structure, reactivity, and biological properties of hidantoines

    International Nuclear Information System (INIS)

    Hydantoin (imidazolidine-2,4-dione) is a 2,4-diketotetrahydroimidazole discovered by Baeyer in 1861. Thiohydantoins and derivatives were prepared, having chemical properties similar to the corresponding carbonyl compounds. Some biological activities (antimicrobial, anticonvulsant, schistosomicidal) are attributed to the chemical reactivity and consequent affinity of hydantoinic rings towards biomacromolecules. Therefore, knowledge about the chemistry of hydantoins has increased enormously. In this review, we present important aspects such as reactivity of hydantoins, acidity of hydantoins, spectroscopy and crystallographic properties, and biological activities of hydantoin and its derivatives. (author)

  7. Sulphasalazine Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

  8. Pharmacologic Therapies in Musculoskeletal Conditions.

    Science.gov (United States)

    Loveless, Melinda S; Fry, Adrielle L

    2016-07-01

    Musculoskeletal conditions are common, and there are many options for pharmacologic therapy. Unfortunately, there is not strong evidence for the use of many of these medications. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are generally first-line medications for most musculoskeletal pain, but there is more evidence these medications are not as safe as once thought. Other analgesic and antispasmodic medications can be effective for acute pain but generally are not as effective for chronic pain. Antidepressants and anticonvulsants can be more effective for chronic or neuropathic pain. Topical formulations of NSAIDs can be effective for pain with fewer side effects. PMID:27235619

  9. Synergistic interaction of levetiracetam with gabapentin in the mouse 6 Hz psychomotor seizure model – a type II isobolographic analysis

    Directory of Open Access Journals (Sweden)

    Wlaz Aleksandra

    2015-09-01

    Full Text Available 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 isobolographic analysis revealed that the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.05 in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive in the mouse 6 Hz psychomotor seizure model. We conclude that, as the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 exerted supra-additive (synergistic interaction in the mouse 6 Hz psychomotor seizure model, this may be considered as particularly favorable combinations in further clinical practice.

  10. Recognition and management of febrile convulsion in children.

    Science.gov (United States)

    Paul, Siba Prosad; Kirkham, Emily Natasha; Shirt, Bethany

    2015-08-26

    Febrile convulsion is characterised by convulsion associated with fever in an infant or child aged between six months and six years. The febrile illness causing the convulsion should not be secondary to an intracranial infection (meningitis or encephalitis) or acute electrolyte imbalance. Most cases of febrile convulsion are short lived and self-terminating. However, a few cases of prolonged febrile convulsion may need anticonvulsant medication to stop the seizure. Management is mainly symptomatic, although anticonvulsants may have a role in a small number of children with complex or recurrent febrile convulsion. Referral to paediatric neurologists may be necessary in cases of complex or recurrent febrile convulsion, or in those where a pre-existing neurological disorder exists. One third of children will develop a further febrile convulsion during subsequent febrile illness. Nurses have a vital role in managing children with febrile convulsion, educating parents about the condition and dispelling myths. This article outlines the presentation, management, investigations and prognosis for febrile convulsion, indicating how nurses working in different clinical areas can help to manage this common childhood condition. PMID:26307316

  11. Treatment and outcome in patients with febrile convulsion associated with epileptiform discharges on electroencephalography.

    Science.gov (United States)

    Okumura, Akihisa; Ishiguro, Yoshiko; Sofue, Ayako; Suzuki, Yoshiko; Maruyama, Koichi; Kubota, Tetsuo; Negoro, Tamiko; Watanabe, Kazuyoshi

    2004-06-01

    The aim of this study is to determine the efficacy of prophylactic treatment for patients with febrile convulsions (FCs) in whom electroencephalograms (EEGs) revealed epileptiform discharges. We retrospectively investigated 43 patients who met the following criteria: (a) at least one FC during the study period; (b) epileptiform discharges were first recognized; (c) no unevoked seizures before epileptiform discharges were first seen; (d) normal psychomotor development and no neurological abnormality; and (e) follow-up >3 years. The clinical characteristics, treatment, and a later occurrence of FCs or unevoked seizures were studied. EEGs revealed focal epileptiform discharges in 25 patients and generalized ones in 18. There was no significant difference in the rate of recurrence of FC or occurrence of unevoked seizures between those with focal and generalized epileptiform discharges. No prophylaxis was performed in ten patients, 14 patients being treated with intermittent diazepam and 19 with a daily anticonvulsant. The rate of recurrence of FC was not significantly different between patients with and without prophylaxis. Unevoked seizures were only observed in two patients undergoing daily treatment. Intermittent or daily anticonvulsant therapy will not reduce the risk of recurrence of FCs or later development of unevoked seizures in patients with FC with epileptiform discharges. PMID:15130690

  12. Antimanic-like effects of (R)-(-)-carvone and (S)-(+)-carvone in mice.

    Science.gov (United States)

    Nogoceke, Francianne P; Barcaro, Inara M R; de Sousa, Damião P; Andreatini, Roberto

    2016-04-21

    Carvone is a monoterpene that is present in spearmint (Mentha spicata) and caraway (Carum carvi) essential oils and has been shown to have anticonvulsant effects, likely through the blockade of voltage-gated sodium channels, and anxiolytic-like effects. Considering that some anticonvulsants that blocked voltage-gated sodium channels (e.g., sodium valproate and carbamazepine) exert clinical antimanic effects, the aim of the present study was to evaluate (R)-(-)-carvone and (S)-(+)-carvone in animal models of mania (i.e., hyperlocomotion induced by methylphenidate and sleep deprivation). Mice that were treated with methylphenidate (5mg/kg) or sleep-deprived for 24h using a multiple-platform protocol exhibited an increase in locomotor activity in an automated activity box. This effect was blocked by pretreatment with acute (R)-(-)-carvone (50-100mg/kg), (S)-(+)-carvone (50-100mg/kg), and lithium (100mg/kg, positive control). These doses did not alter spontaneous locomotor activity in the methylphenidate-induced experiments while (S)-(+)-carvone decreased spontaneous locomotor activity in sleep deprivation experiment, indicating a sedative effect. Chronic 21-day treatment with (R)-(-)-carvone (100mg/kg), (S)-(+)-carvone (100mg/kg), and lithium also prevented methylphenidate-induced hyperactivity. The present results suggest that carvone may have an antimanic-like effect. PMID:26970377

  13. Progress in studies on the role of gamma-aminobutyric acid type A receptor in convulsion: a short review

    Institute of Scientific and Technical Information of China (English)

    LI Xing-fang; LIU Li-qun

    2012-01-01

    Convulsion is the medical condition where body muscles contract and relax rapidly and repeatedly,resulting in an uncontrolled shaking of the body.The impaired inhibition of electrical activity in the brain is one of leading causes of convulsion.y-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system (CNS).GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and post-synaptic neuronal processes.GABAA receptor (GABAAR) is the most important inhibitory receptor,and is the target receptor of anticonvulsant drugs in the clinic.In this review,we describe GABAergic signaling mediated by GABAAR,the mechanisms of GABAAR and their expression,and the progress being made on understanding the role of GABAAR in convulsion with emphasis on the association between GABAAR mutations or GABAAR subunit expression and convulsion.We also describe progress of anticonvulsant drugs based on the GABAAR.

  14. Screening of Methanol Extract and Ethyl Acetate Fraction of Abies webbiana Lindl. for Neuropharmacological Activities

    Directory of Open Access Journals (Sweden)

    O Parkash

    2015-01-01

    Full Text Available Despite a long traditional of use of Abies webbiana Lindl. (Talispatra; family-Pinaceae in the treatment of mental disorders, the plant has not been investigated systematically to validate its traditional claims. Thus, the present investigation was undertaken with an objective to investigate neuropharmacological activities of methanol extract of Abies webbiana aerial parts and its ethyl acetate fraction. Properly identified aerial parts were defatted with petroleum ether and then extracted with methanol in a Soxhlet apparatus. Ethyl acetate fraction was prepared by partitioning methanol extract with ethyl acetate using standard procedure. In acute toxicity study, no mortality was observed in animals after oral administration of 2 g/kg dose of methanol extract. The methanol extract (200 or 400 mg/kg, p.o. and ethyl acetate fraction (25 or 50 mg/kg, p.o. were evaluated for antianxiety, anticonvulsant, antidepressant, sedative, antistress and analgesic activities using well established models. The methanol extract and ethyl acetate fraction of Abies webbiana aerial parts exhibited significant antianxiety, anticonvulsant, antidepressant, sedative, antistress and analgesic activities with respect to control. Preliminary phytochemical screening showed presence of flavonoids in bioactive ethyl acetate fraction of Abies webbiana aerial parts. It is finally concluded that flavonoids are the bioactive constituents responsible for most of neuropharmacological activities of Abies webbiana.

  15. Plant-Derived and Endogenous Cannabinoids in Epilepsy.

    Science.gov (United States)

    Verrotti, Alberto; Castagnino, Miriam; Maccarrone, Mauro; Fezza, Filomena

    2016-05-01

    Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century. The aim of this reveiw was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body. General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as "grand mal." They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner. In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy. Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development. PMID:26892745

  16. Ayurveda and botanical drugs for epilepsy: Current evidence and future prospects.

    Science.gov (United States)

    Sriranjini, Sitaram Jaideep; Sandhya, Kumar; Mamta, Vernekar Sanjeeva

    2015-11-01

    The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy". PMID:26141933

  17. Traceless Synthesis of Hydantoin by Focused Microwave Irradiation

    Institute of Scientific and Technical Information of China (English)

    Lee Ming-juan; SUN Chung-ming

    2004-01-01

    Hydantoin analogs have shown versatile therapeutic applications and some of them have been approved by FDA as drugs. For example, Fosphenytoin as a sodium channel antagonist is used for the treatment of epilepsy. Phenytoin has antiarrhythmic, anticonvulsant and antineuralgic activities. Ethotoin and Mephenytoin both show anticonvulsant effect. Nilutamide is a non-steroidal orally-active antiandrogen in combination with surgical castration for the treatment of stage D2 metastatic prostate cancer. (Figure 1)An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of hydantoins is presented. Nucleophilic substitution of poly (ethylene glycol) immobilized chloroacetyl group with several primary amines is carried out in dichloromethane under microwave cavity. After introduction of various isocyanates, the cyclization/ cleavage step can be performed in mild basic condition by microwave flash heating. Compared to conventional thermal hearting,microwave irradiation decreased the reaction time on the support from several hours to several minutes. The coupling of microwave technology with liquid phase combinatorial synthesis constitutes a novel and attractive avenue for the rapid generation of structurally diverse libraries in good yield and high purity.

  18. New onset seizures in the elderly: aetiology and prognosis.

    LENUS (Irish Health Repository)

    Timmons, S

    2012-02-03

    Late onset epilepsy is increasing in incidence. These patients often have significant underlying morbidity. This retrospective study in a tertiary referral centre identified 68 patients aged 65 years or older, with new onset seizures over a four-year period. 81% of patients (n = 55) were followed up at an average of 2.7 years post diagnosis. 38% of patients had evidence of cerebrovascular disease (CT visualised focal infarction, haemorrhage or small vessel ischaemia in 32%, clinical diagnosis with normal CT brain in 6%). No patient was found to have a space-occupying lesion. Of the 55 patients followed up, 45% of these had died at a mean age of 82 years old and 1.9 years post diagnosis (range 12 hours to 5 years). Three patients died as a direct result of seizures (trauma and sepsis). 14 patients died of clearly unrelated causes. Eight patients died from underlying vascular disease or Alzheimer\\'s dementia. Patients who died during follow-up were on average 3.4 years older at the time of diagnosis than survivors (p< 0.05). Patients with atrial fibrillation at the time of diagnosis, had increased mortality (relative risk 2.53; 95% C.I. 1.19 - 5.36), but they were older than those without atrial fibrillation. At the time of follow up, 92% of those taking anti-convulsants were maintained seizure free on anticonvulsant monotherapy.

  19. Medication use and potential drug interactions in pediatric patients with infectious diseases.

    Science.gov (United States)

    Lisby, S M; Nahata, M C

    1987-04-01

    Infectious diseases are the most common type of illness in pediatric patients. Limited data are available, however, about the most frequently prescribed drugs for children in pediatric infectious diseases units. The authors prospectively evaluated medication records of 493 children over a 5-month period to determine the pattern of drug prescribing and incidence of potential drug interactions in children admitted to the infectious diseases unit in a pediatric hospital. Antimicrobial agents were the most frequently prescribed class of drugs, comprising 60% of all drug orders. Of all antibiotics used during this period, ampicillin was the most common (24% of antibiotic orders). Ceftriaxone, cefuroxime, and gentamicin were also used frequently and consisted of 15%, 10%, and 14% of all orders for anti-infective agents, respectively. Other classes of drugs frequently given to patients on the infectious disease unit were antipyretics (14%), bronchodilators (10%), and anticonvulsants (7%). The incidence of potential drug interactions was 3.5%, the majority involving anticonvulsants. A clinically significant drug interaction was not documented in any of these cases. Observations made from this study may assist in developing clinical pharmacy services and educational programs for pharmacy students. In addition, knowledge of drug use patterns may aid in conducting antibiotic use reviews. PMID:10281735

  20. Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative

    International Nuclear Information System (INIS)

    The antagonist effect of ±-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the receptor complex. When the enantiomers of ±-HA-966 were resolved, the (R)-(+)-enantiomer was found to be a selective glycine/NMDA receptor antagonist, a property that accounts for its anticonvulsant activity in vivo. In contrast, the (S)-(-)-enantiomer was only weakly active as an NMDA-receptor antagonist, but nevertheless it possessed a marked sedative and muscle relaxant action in vivo. In radioligand binding experiments, (+)-HA-966 inhibited strychnine-insensitive [3H]glycine binding to rat cerebral cortex synaptic membranes with an IC50 of 12.5 μM, whereas (-)-HA-966 had an IC50 value of 339 μM. In mice, (+)-HA-966 antagonized sound and N-methyl-DL-aspartic acid (NMDLA)-induced seizures. The coadministration of D-serine dose-dependently antagonized the anticonvulsant effect of a submaximal dose of (+)-HA-966 against NMDLA-induced seizures. The sedative/ataxic effect of racemic HA-966 was mainly attributable to the (-)-enantiomer. It is suggested that, as in the case of the sedative γ-butyrolactone, disruption of striatal dopaminergic mechanisms may be responsible for this action

  1. Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative

    Energy Technology Data Exchange (ETDEWEB)

    Singh, L.; Donald, A.E.; Foster, A.C.; Hutson, P.H.; Iversen, L.L.; Iversen, S.D.; Kemp, J.A.; Leeson, P.D.; Marshall, G.R.; Oles, R.J.; Priestley, T.; Thorn, L.; Tricklebank, M.D.; Vass, C.A.; Williams, B.J. (Merck Sharp and Dohme Research Labs., Essex (England))

    1990-01-01

    The antagonist effect of {+-}-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the receptor complex. When the enantiomers of {+-}-HA-966 were resolved, the (R)-(+)-enantiomer was found to be a selective glycine/NMDA receptor antagonist, a property that accounts for its anticonvulsant activity in vivo. In contrast, the (S)-(-)-enantiomer was only weakly active as an NMDA-receptor antagonist, but nevertheless it possessed a marked sedative and muscle relaxant action in vivo. In radioligand binding experiments, (+)-HA-966 inhibited strychnine-insensitive ({sup 3}H)glycine binding to rat cerebral cortex synaptic membranes with an IC{sub 50} of 12.5 {mu}M, whereas (-)-HA-966 had an IC{sub 50} value of 339 {mu}M. In mice, (+)-HA-966 antagonized sound and N-methyl-DL-aspartic acid (NMDLA)-induced seizures. The coadministration of D-serine dose-dependently antagonized the anticonvulsant effect of a submaximal dose of (+)-HA-966 against NMDLA-induced seizures. The sedative/ataxic effect of racemic HA-966 was mainly attributable to the (-)-enantiomer. It is suggested that, as in the case of the sedative {gamma}-butyrolactone, disruption of striatal dopaminergic mechanisms may be responsible for this action.

  2. Effect of Nifedipine on Dichlorvos-Induced Seizure in Mice

    Directory of Open Access Journals (Sweden)

    Khayatnouri Mirhadi

    2011-01-01

    Full Text Available Problem statement: Dichlorvos a synthetic organophosphate poisons is the property of insecticide. These toxins as insecticides in agriculture and medicine for animals and the destruction of ectoparasites can be used. Studies have shown that Dichlorvos creation seizure effects in different animals. Nifedipine, dihydropyridine calcium channel blockers, widely used for treatment of cardiovascular diseases. Studies have shown that the calcium channel blockers are anticonvulsant effects in different animal models. The aim of this study was to determine the effect of nifedipine on Dichlorvosinduced seizures in mice. Approach: In this experiment, the animals were received different doses of nifedipine (2.5, 5, 10, 20 and 40 mg kg-1 intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg kg-1. After Dichlorvos injection, clonic and tonic seizures and death was investigated. Results: Results showed that nifedipine dose dependently reduced the severity of Dichlorvos-induced seizures, so that nifedipine dose 10 and 40 mg kg-1, respectively, the lowest (pConclusion: The anticonvulsant activity of nifedipine suggests that possibly due to antagonistic effect on voltage-dependent calcium channel.

  3. [New antiepileptic drugs, and therapeutic considerations].

    Science.gov (United States)

    Szupera, Zoltán

    2011-09-30

    Epilepsy is not a singular disease, but a variety of disorders. It affects up to 0.5% of the population. Over the past decade, researchers have made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced to the market. Retigabine is a carbamic derivate, and its anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. Lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. Eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appear to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it will take the consideration of new concepts in shaping the new therapeutic algorithm. PMID:22059370

  4. Adenosine receptor modulation of seizure susceptibility in rats

    International Nuclear Information System (INIS)

    Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A1 adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of 3H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A1 adenosine receptors in the cerebral cortex

  5. Non-adenosine nucleoside inosine, guanosine and uridine as promising antiepileptic drugs: a summary of current literature.

    Science.gov (United States)

    Kovacs, Zsolt; Kekesi, Katalin A; Juhasz, Gabor; Barna, Janos; Heja, Laszlo; Lakatos, Renata; Dobolyi, Arpad

    2015-01-01

    Adenosine (Ado) and some non-adenosine (non-Ado) nucleosides including inosine (Ino), guanosine (Guo) and uridine (Urd) are modulatory molecules in the central nervous system (CNS), regulating different physiological and pathophysiological processes in the brain such as sleep and epilepsy. Indeed, different drugs effective on adenosinergic system (e.g., Ado metabolism inhibitors, agonists and antagonists of Ado receptors) are being used in drug development for the treatment of epileptic disorders. Although (i) endogenous Ino, Guo and Urd showed anticonvulsant/antiepileptic effects (e.g., in quinolinic acid - induced seizures and in different epilepsy models such as hippocampal kindling models), and (ii) there is a need to generate new and more effective antiepileptic drugs for the treatment of drug-resistant epilepsies, our knowledge about antiepileptic influence of non-Ado nucleosides is far from complete. Thus, in this review article, we give a short summary of anticonvulsant/antiepileptic effects and mechanisms evoked by Ino, Guo, and Urd. Finally, we discuss some non-Ado nucleoside derivatives and their structures, which may be candidates as potential antiepileptic agents. PMID:25382017

  6. [Impact of early benefit assessment on patients with epilepsy in Germany : Current healthcare provision and therapeutic needs].

    Science.gov (United States)

    Strzelczyk, A; Hamer, H M

    2016-04-01

    Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system. PMID:26927680

  7. Experimental models of epilepsy

    Directory of Open Access Journals (Sweden)

    Stanojlović Olivera P.

    2004-01-01

    Full Text Available Introduction An epileptic seizure is a clinical event and epilepsy is rather a group of symptoms than a disease. The main features all epilepsies have in common include: spontaneous occurrence, repetitiveness, and ictal correlation within the EEG. Epilepsies are manifested with distinct EEG changes, requiring exact clinical definition and consequential treatment. Current data show that 1% of the world's population (approximately 50 million people suffers from epilepsy, with 25% of patients being refractory to therapy and requiring search for new substances in order to decrease EEG and behavioral manifestations of epilepsies. Material and methods In regard to discovery and testing of anticonvulsant substances the best results were achieved by implementation of experi- mental models. Animal models of epilepsy are useful in acquiring basic knowledge regarding pathogenesis, neurotransmitters (glutamate, receptors (NMDA/AMPA/kainate, propagation of epileptic seizures and preclinical assessment of antiepileptics (competitive and non-competitive NMDA antagonists. Results and conclusions In our lab, we have developed a pharmacologic model of a (metaphit, NMDA and remacemide-cilastatin generalized, reflex, and audiogenic epilepsy. The model is suitable for testing various anticonvulsant substances (e.g. APH, APV, CPP, Mk-801 and potential antiepileptics (e.g. DSIP, its tetra- and octaanalogues.

  8. Uncaria rhynchophylla and rhynchophylline improved kainic acid-induced epileptic seizures via IL-1β and brain-derived neurotrophic factor.

    Science.gov (United States)

    Ho, Tin-Yun; Tang, Nou-Ying; Hsiang, Chien-Yun; Hsieh, Ching-Liang

    2014-05-15

    Uncaria rhynchophylla (UR) has been used for the treatment of convulsions and epilepsy in traditional Chinese medicine. This study reported the major anti-convulsive signaling pathways and effective targets of UR and rhynchophylline (RP) using genomic and immunohistochemical studies. Epileptic seizure model was established by intraperitoneal injection of kainic acid (KA) in rats. Electroencephalogram and electromyogram recordings indicated that UR and RP improved KA-induced epileptic seizures. Toll-like receptor (TLR) and neurotrophin signaling pathways were regulated by UR in both cortex and hippocampus of KA-treated rats. KA upregulated the expression levels of interleukin-1β (IL-1β) and brain-derived neurotrophin factor (BDNF), which were involved in TLR and neurotrophin signaling pathways, respectively. However, UR and RP downregulated the KA-induced IL-1β and BDNF gene expressions. Our findings suggested that UR and RP exhibited anti-convulsive effects in KA-induced rats via the regulation of TLR and neurotrophin signaling pathways, and the subsequent inhibition of IL-1β and BDNF gene expressions. PMID:24636743

  9. Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

    Institute of Scientific and Technical Information of China (English)

    Li-ping ZHANG; Li WANG

    2005-01-01

    Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y1, Y2, and Y5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was foundin tolerant and dependent rats. The level ofpreproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures.Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3, and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y1 and Y5 decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y2 increased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y1, Y2, and Y5 mRNA were also altered in FZP tolerance and dependence.

  10. The Use of Central Nervous System Active Drugs During Pregnancy

    Directory of Open Access Journals (Sweden)

    Bengt Källén

    2013-10-01

    Full Text Available CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011 are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found.

  11. Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine

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    Rivelilson Mendes de Freitas

    2011-06-01

    Full Text Available The aim of this study was to evaluate the in vitro antioxidant effects of 12-[(2R,5R,6R-5-hydroxy-6-methylpiperidin-2-yl]dodecan-2-one (iso-6-cassine; ISO and the anticonvulsant effects of ISO on pilocarpine-induced seizures in rats. Wistar rats were treated with 0.9% saline (i.p., control group, pilocarpine (400 mg/kg, i.p., pilocarpine group, and the association of ISO (1.0 mg/kg, i.p. plus pilocarpine (400 mg/kg, i.p., 30 min after administration of ISO (ISO plus pilocarpine group. After the treatments all groups were observed for 1h. The antioxidant effect of ISO on the pilocarpine model was assessed by determining the activity of glutathione peroxidase (GPx, glutathione-S-transferase (GST and catalase (CAT as well as the levels of reactive species (RS and lipid peroxidation (LP. In vitro, ISO (5 μM reduced RS and LP. ISO (1.0 mg/kg and abolished seizures and death induced by pilocarpine in rats. ISO protected against the increase in the RS and LP levels, GST activity as well as the inhibition of GPx activity caused by pilocarpine. In addition, ISO increased the catalase activity in hippocampus of seized rats. In conclusion, the dta suggest that ISO can present anticonvulsant and antioxidant properties in the pilocarpine model of seizures in rats.

  12. Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

    Science.gov (United States)

    Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2016-09-01

    Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID:27413119

  13. Phenytoin Induced Osteopathy -Too Common to be Neglected.

    Science.gov (United States)

    Patil, Milind Machhindra; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar; Pillai, Vivekanandan

    2015-11-01

    Anticonvulsants have the broad spectrum of side effects on the bone that are collectively known as osteopathy. Anticonvulsant induced osteopathy can have detrimental consequences. We present an unusual case that uniquely highlights both adverse effects of phenytoin on bone metabolism and side effects of its overtreatment. A 29-year-old lady came for evaluation of metabolic bone disease. Since last one year, she had severe bilateral hip pain resulting in restriction of movements. She was taking phenytoin 300 mg daily for last ten years for a seizure disorder. During evaluation at another center, she was diagnosed to have vitamin D deficiency, osteomalacia and secondary hyperparathyroidism. She received recombinant parathormone, high doses of vitamin D along with phenytoin. She presented at our centre with persistent pain and hypervitaminosis D. We stopped recombinant PTH, vitamin D and changed phenytoin to levetiracetam. Her condition improved over next six months with normalization of vitamin D. Thus, patients on phenytoin should be actively screened for side effects and the appropriate preventive and correctional measures should be undertaken. While managing these side effects overtreatment should be avoided. PMID:26674262

  14. Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.

    Science.gov (United States)

    Sakkaki, Sophie; Gangarossa, Giuseppe; Lerat, Benoit; Françon, Dominique; Forichon, Luc; Chemin, Jean; Valjent, Emmanuel; Lerner-Natoli, Mireille; Lory, Philippe

    2016-02-01

    T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection. PMID:26456350

  15. Clinical use of pregabalin in the management of central neuropathic pain

    Directory of Open Access Journals (Sweden)

    Nanna B Finnerup

    2007-01-01

    Full Text Available Nanna B Finnerup, Troels S JensenDanish Pain Research Center, Department of Neurology, Aarhus University Hospital, Aarhus, DenmarkAbstract: Central neuropathic pain (central pain is treated with antidepressants, various anticonvulsants, opioids, and cannabinoids, but in many cases treatment is insufficient and associated with a range of side-effects. This review addresses a new treatment for neuropathic pain, the anticonvulsant pregabalin. We review the pharmacology, mode of action, pharmacokinetics, and safety of pregabalin as well as two randomized efficacy studies in central pain and a brief overview of efficacy in peripheral neuropathic pain. Pregabalin appears to have efficacy in treating central pain comparable to that in peripheral neuropathic pain as well as efficacy of other recommended drugs for central pain. Pregabalin also improves disturbed sleep and anxiety. Pregabalin is well tolerated; the most common side-effects are somnolence, dizziness, ataxia, and weight gain. Pregabalin is suitable for patients on multiple drugs although there may be additive CNS-related side-effects. Thus, pregabalin has a primary role in central pain patients.Keywords: central pain, neuropathic pain, pregabalin, pharmacology

  16. Cancer risk in long-term users of valproate: a population-based case-control study

    DEFF Research Database (Denmark)

    Hallas, Jesper; Friis, Søren; Bjerrum, Lars;

    2009-01-01

    BACKGROUND: Inhibitors of histone deacetylases (HDAC) have shown promise as targeted cancer therapy. Valproate, an older anticonvulsant, has been shown to possess HDAC inhibitory activity. We undertook this case-control study to clarify whether long-term users of valproate had a reduced cancer in......-term valproate use is not associated with a reduced cancer risk. Our study does not support HDAC inhibition as a pharmacologic principle for general chemoprevention.......BACKGROUND: Inhibitors of histone deacetylases (HDAC) have shown promise as targeted cancer therapy. Valproate, an older anticonvulsant, has been shown to possess HDAC inhibitory activity. We undertook this case-control study to clarify whether long-term users of valproate had a reduced cancer...... incidence. If so, it would support HDAC inhibition as a pharmacologic principle in chemoprevention. METHODS: We identified 149,417 incident cancer cases in Denmark during the study period 2000 through 2005, and 597,668 age- and gender-matched controls. Data on history of cancer, past hospital admission...

  17. In vivo screening of essential oils of Skimmia laureola leaves for antinociceptive and antipyretic activity

    Institute of Scientific and Technical Information of China (English)

    Naveed Muhammad; Barkatullah; Muhammad Ibrar; Haroon Khan; Muhammad Saeed; Amir Zada Khan; Waqar Ahmad Kaleem

    2013-01-01

    Objective:To study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models. Methods: SLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively. Results: Substantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48%at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole. Conclusions:In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.

  18. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    Science.gov (United States)

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  19. The Pharmacological Basis of Cannabis Therapy for Epilepsy.

    Science.gov (United States)

    Reddy, Doodipala Samba; Golub, Victoria M

    2016-04-01

    Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. PMID:26787773

  20. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics.

    Science.gov (United States)

    Ernst, Carrie L; Goldberg, Joseph F

    2002-01-01

    There has been growing concern about the potential iatrogenic effects of several newer psychotropic drugs on reproductive health safety in women. Areas of particular concern in this regard include (1) controversies about a potential association between the use of valproate and development of polycystic ovary syndrome (PCOS), (2) the safety of use of newer psychotropic medications during pregnancy, and (3) safety issues with these medications in women while breastfeeding. This review summarizes current information about each of these areas. In particular, existing data suggest that (1) PCOS very likely represents a complex neuroendocrine disorder with multiple determinants; (2) menstrual irregularities may be a frequently seen phenomenon in women with bipolar illness, at least partially independent of psychotropic drug therapy; (3) potential central nervous system teratogenicity remains substantial during first-trimester exposure to valproate or carbamazepine; (4) with newer agents used for bipolar disorder and schizophrenia, safety data during pregnancy, while not definitive, are most abundant with olanzapine and with lamotrigine; relatively less is known about systematic pregnancy outcomes with other atypical antipsychotics or newer anticonvulsants; and (5) risks for neonatal safety during lactation continue to appear substantial with lithium, are of potential concern with lamotrigine and clozapine, are quite likely minimal with valproate or carbamazepine, and are indeterminate with most other new anticonvulsants or atypical antipsychotics. Recommendations are presented for clinical management in each of these instances. PMID:11913676