WorldWideScience

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. Anticonvulsants for tinnitus (Review)

    NARCIS (Netherlands)

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

    2011-01-01

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

  3. 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

  4. Succinimides: Synthesis, properties and anticonvulsant activity

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    Banjac Nebojša

    2011-01-01

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

  5. 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 ...

  6. Lactation studies of anticonvulsants : A quality review

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. 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.

  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. [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)

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. [Anticonvulsant and psychotropic effects of topamax capsules].

    Science.gov (United States)

    Kalinin, V V; Zheleznova, E V; Sokolova, L V; Zemlianaia, A A

    2009-01-01

    Anticonvulsant and psychotropic effects of "Topamax capsules"(TC) were compared to a traditional form of topiramate (TFT) and some other anticonvulsant drugs (ACD). Thirty-six patients (12 men and 24 women) with partial temporary epilepsy were examined. Sixteen patients received TFT in tablets and 20 patients received ACD before the beginning of the study. Drug effect was assessed by frequency of seizures and some neuropsychiatric parameters. The results revealed that TC was comparable to TFT and ACD in the reduction of seizures of any semiotics. After 3 months of therapy, total MMSE scores increased from 27 to 28. There were less perseverant errors and more right responses in the WCST. Verbal fluency and memory measured with Sunderland test improved as well. TC led to decreased latencies of negative responses in the WCST and increased verbal fluency compared to TFT. Patients who received TFT prior to TC did fewer errors in the WCST than patients who received ACD prior to TC. Verbal fluency improved compared to patients who received other ACD. At the same time, a somewhat increase of paranoid signs on the scale SCL-90 was noted in the group treated with topiramate only. It has been concluded that TC has an activating effect on frontal brain areas.

  16. 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...

  17. Anticonvulsant activities of nutmeg oil of Myristica fragrans.

    Science.gov (United States)

    Wahab, Abdul; Ul Haq, Rizwan; Ahmed, Aftab; Khan, Rafeeq Alam; Raza, Mohsin

    2009-02-01

    The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 microL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD(50) (2150 microL/kg) value was much higher than its anticonvulsant doses (50-300 microL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures. PMID:19067329

  18. 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.

  19. Anticonvulsant and antipunishment effects of toluene

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-01-01

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

  20. Anticonvulsant properties of saponins from Ficus platyphylla stem bark.

    Science.gov (United States)

    Chindo, Ben A; Anuka, Joseph A; McNeil, Lilly; Yaro, Abdullahi H; Adamu, Simon S; Amos, Samson; Connelly, William K; Lees, George; Gamaniel, Karniyus S

    2009-03-30

    Preparations of Ficus platyphylla have been used in Nigerian traditional medicine for the management of epilepsy for many years and their efficacy is widely acclaimed among the Hausa communities of northern Nigeria. The anticonvulsant properties of the saponin rich fraction (SFG) obtained from the methanol extract of F. platyphylla stem bark were studied on pentylenetetrazole-, strychnine- and maximal electroshock seizures in mice. Effects of SFG were also examined in murine models for neurological disease and on relevant in vitro targets for anticonvulsant drugs. SFG protected mice against pentylenetetrazole- and strychnine-induced seizures; and significantly delayed the onset of myoclonic jerks and tonic seizures. SFG failed to protect mice against maximal electroshock seizures at doses tested. SFG neither abolished the spontaneous discharges induced by 4-aminopyridine in a neonatal rat brain slice model of tonic-clonic epilepsy nor could it modulate chloride currents through GABA(A) receptor channel complex in cultured cortical cells. However, it was able to non-selectively suppress excitatory and inhibitory synaptic traffic, blocked sustained repetitive firing (SRF) and spontaneous action potential firing in these cultured cells. Our results provide scientific evidence that F. platyphylla stem bark may contain psychoactive principles with potential anticonvulsant properties. SFG impaired membrane excitability; a property shared by most anticonvulsants particularly the voltage-gated sodium channel (VGSC) blocking drugs, thus supporting the isolation and development of the saponin components of this plant as anticonvulsant agents.

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

    Science.gov (United States)

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

    2013-12-01

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

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    Sudhakara Rao Gerapati

    2015-09-01

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

  4. Anticonvulsant activity of aqueous extract of Leonotis leonurus.

    Science.gov (United States)

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

    2002-04-01

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

  5. 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...

  6. Design and synthesis of some novel 4-(4-substituted aryl semicarbazones as anticonvulsant agents

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    Singh Anita

    2010-01-01

    Full Text Available In the present study, a series of 4-(4-substituted aryl semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD programme NIH, USA using experimental animal, adult male FCM mice (20-25 g and adult Sprague-Dawley rats (100-150 g and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity.

  7. 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.

  8. SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME NOVEL SEMICARBAZONE DERIVATIVES CONTAINING QUINOXALINE MOIETY

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    Rakesh Sahu*, Sonal Tiwari, Jay Kumar Chandra and Prabhat Kumar Patel

    2012-11-01

    Full Text Available Various 1-(substituted benzylidene-5-(3-hydroxyquinoxaline-2-yl carbonohydrazide were synthesized starting from orthophenylenediamine. Structures of all the compounds were confirmed on the basis of spectral analyses. All the newly synthesized compounds were screened for anticonvulsant activity. Some of the compounds showed significant anticonvulsant activity with no neurotoxicity

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    AGGARWAL Navneet; MISHRA Pradeep

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bhawna Sharma

    2013-01-01

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

  12. Synthesis and Anticonvulsant Activity of Some Newer Semicarbazone Derivatives

    Directory of Open Access Journals (Sweden)

    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.

  13. [Neuropeptide thyroliberin--an endogenous anticonvulsant in the brain].

    Science.gov (United States)

    Chepurnov, S A; Chepurnova, N E; Abbasova, K R; Goncharov, O B

    2002-01-01

    Thyroliberin (TRH) promoting endogenous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application. This application TRH in ultra-low doses contrast the method of systemic TRH administration (i.v., i.m. or oral in the large doses--mg). In our experiments intranasal application of 10(-9) M, 10(-10) M and 10(-12) M TRH significantly inhibited the severe epileptic motor fits in rats induced by pentylenetetrazole (PTZ). Beneficent effect of TRH is also confirmed by EEG (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide cHis-Pro-NH2 (10(-10) M, 10(-5) M). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology. PMID:11881332

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

    Directory of Open Access Journals (Sweden)

    Abolfazl MAHYAR

    2011-12-01

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

  15. [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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro...

  19. Anticonvulsant activity of methanolic and aqueous extracts of Melissa parviflora in experimentally induced Swiss albino mice

    OpenAIRE

    Ahmad, Shiekh Tanveer; Asiaf, Asia; Aslam, Mohammad; Bhat, Jalal Uddin; Khanam, Razia; Mujeeb, Mohammad; Nizami, Qudsia; Parray, Shabir Ahmad; Siddiqui, Aisha; Umar, Sadiq

    2012-01-01

    The aim of the present study was to evaluate the anticonvulsant effect of whole plant extracts of Melissa parviflora using MES and PTZ induced seizures models. The dried whole plant was subjected to extraction in methanol and water. The extracts were subjected to phytochem-ical tests and the carbohydrate, flavonols, coumarins, glycosides and steroid were found to be present. The methanolic and aqueous extracts of the plant of Melissa parviflora were observed for their anticonvulsant activity ...

  20. 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

  1. 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...

  2. 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.

  3. Combination anticonvulsant treatment of soman-induced seizures.

    Science.gov (United States)

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

    2001-12-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  5. Anticonvulsant properties of spirohydantoins derived from optical isomers of camphor.

    Science.gov (United States)

    Chatterjie, N; Alexander, G J

    1986-12-01

    Natural camphor exists as the d (+) form but the l (-) form has been synthesized. Replacement of the keto group on carbon 2 of each form with a hydantoin moiety led to only one spirohydantoin derivative. Both d and l derivatives were synthesized. Both forms and their racemic mixture were tested in vivo for toxicity and behavioral effects in mice. A dose of 100 mg/kg of the d form was not toxic: mice showed normal grooming and exploratory behavior; the l form induced hunched posture, body jerks and myoclonic manifestations followed by quiescence. The dl form showed intermediate effects. Challenge with the convulsant pentylenetetrazol (Metrazol) 2 hr after treatment with placebo or the camphor spirohydantoins produced seizure manifestations in all controls, in half of the subjects pretreated with the d-camphor derivative, in none of those pretreated with the l derivative and an intermediate response in those pretreated with racemic mixture. Thus, a spirohydantoin moiety added to camphor conferred strong anticonvulsive properties on the l form and modest ones on the d form; the d form did not seem to antagonize the l form. PMID:3822049

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

    Directory of Open Access Journals (Sweden)

    Franklin F. F. Nóbrega

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad TORKAMAN

    2012-03-01

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

  8. 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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    -based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti...

  10. Anticonvulsant activity of Harpagophytum procumbens DC [Pedaliaceae] secondary root aqueous extract in mice.

    Science.gov (United States)

    Mahomed, Ismail M; Ojewole, John A O

    2006-03-15

    Harpagophytum procumbens DC [family: Pedaliaceae] is widely used in South African traditional medicine for the treatment, management and/or control of a variety of human ailments. In the present study, we have examined the anticonvulsant activity of Harpagophytum procumbens secondary root aqueous extract (HPE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Like the reference anticonvulsant agents used, H. procumbens secondary root aqueous extract (HPE, 100-800 mg/kg i.p.) significantly (P<0.05-0.001) delayed the onset of, and antagonized, pentylenetetrazole (PTZ)-induced seizures. The plant's extract (HPE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but only partially and weakly antagonized bicuculline (BCL)-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that H. procumbens secondary root aqueous extract (HPE) produces its anticonvulsant activity by enhancing GABAergic neurotransmission and/or facilitating GABAergic action in the brain. In general, the average onset of convulsion was delayed, while the average duration of convulsion was markedly reduced. The plant's extract also depressed the central nervous system (CNS). It is, therefore, thought that the anticonvulsant property of the herb may be linked, at least in part, to its ability to depress the central nervous system. However, the results of this experimental animal study indicate that H. procumbens secondary root aqueous extract possesses anticonvulsant activity, and thus lend pharmacological support to the suggested folkloric, ethnomedical uses of the plant's extract in the treatment, management and/or control of epilepsy and childhood convulsions in some rural communities of South Africa. PMID:16464685

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Patrick Amoateng

    2012-01-01

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

  13. 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.

  14. A role for ATP-sensitive potassium channels in the anticonvulsant effects of triamterene in mice.

    Science.gov (United States)

    Shafaroodi, Hamed; Barati, Saghar; Ghasemi, Mehdi; Almasirad, Ali; Moezi, Leila

    2016-03-01

    There are reports indicating that diuretics including chlorothiazide, furosemide, ethacrynic acid, amiloride and bumetanide can have anticonvulsant properties. Intracellular acidification appears to be a mechanism for the anticonvulsant action of some diuretics. This study was conducted to investigate whether or not triamterene, a K(+)-sparing diuretic, can generate protection against seizures induced by intravenous or intraperitoneal pentylenetetrazole (PTZ) models. And to see if, triamterene can withstand maximal electroshock seizure (MES) in mice. We also investigated to see if there is any connection between triamterene's anti-seizure effect and ATP-sensitive K(+) (KATP) channels. Five days triamterene oral administration (10, 20 and 40 mg/kg), significantly increased clonic seizure threshold which was induced by intravenous pentylenetetrazole. Triamterene (10, 20 and 40 mg/kg) treatment also increased the latency of clonic seizure and decreased its frequency in intraperitoneal PTZ model. Administration of triamterene (20 mg/kg) also decreased the incidence of tonic seizure in MES-induced seizure. Co-administration of a KATP sensitive channel blocker, glibenclamide, in the 6th day, 60 min before intravenous PTZ blocked triamterene's anticonvulsant effect. A KATP sensitive channel opener, diazoxide, enhanced triamterene's anti-seizure effect in both intravenous PTZ or MES seizure models. At the end, triamterene exerts anticonvulsant effect in 3 seizure models of mice including intravenous PTZ, intraperitoneal PTZ and MES. The anti-seizure effect of triamterene probably is induced through KATP channels. PMID:26855365

  15. 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.)

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

    Science.gov (United States)

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

    2012-03-01

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

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

    NARCIS (Netherlands)

    Beenen, L F; Lindeboom, J; Kasteleijn-Nolst Trenité, D G; Heimans, J J; Snoek, F J; Touw, D J; Adèr, H J; van Alphen, H A

    1999-01-01

    OBJECTIVE: To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy. METHODS: A prospective, stratified, randomised, double blind single centre clinical trial was per

  18. 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...

  19. 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...

  20. Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents

    Directory of Open Access Journals (Sweden)

    Zhiming Wang

    2015-09-01

    Full Text Available A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES and subcutaneous pentylenetetrazole (scPTZ test. The activity experimental study showed that 2,2-dipropyl-N1-(4-sulfamoylphenylmalonamide (18b had the lowest median effective dose (ED50 of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenylcyclopropane-1,1-dicarboxamide (12c had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy.

  1. 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.

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

    Science.gov (United States)

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

    2016-10-15

    Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (Ptest (Psleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect. PMID:27475676

  3. 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

  4. 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

  5. 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

  6. 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...

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

    Directory of Open Access Journals (Sweden)

    Shakya Ashok K.

    2016-09-01

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

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

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

    Science.gov (United States)

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

    2001-10-01

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

  18. 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.

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

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    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.

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

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    Ali Yadollahpour

    2015-02-01

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

  1. Anticonvulsant effect of Rhus chirindensis (Baker F.) (Anacardiaceae) stem-bark aqueous extract in mice.

    Science.gov (United States)

    Ojewole, John A O

    2008-04-17

    Extracts of Rhus chirindensis stem-bark are used extensively in South African traditional medicines for the treatment, management and/or control of an array of human ailments, including childhood convulsions and epilepsy. In this study, we investigated the anticonvulsant activity of the plant's stem-bark aqueous extract (RCE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Single intraperitoneal injections of PTZ (90 mg/kg), PCT(10 mg/kg) or BCL (30 mg/kg) produced tonic-clonic seizures. Like the standard antiseizure drugs used, Rhus chirindensis stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) significantly delayed (pbark aqueous extract (RCE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin-induced seizures, but only weakly antagonized bicuculline-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that RCE produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results of this laboratory animal study indicate that RCE possesses anticonvulsant activity in the mammalian experimental model used, and thus suggest that the plant may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions and epilepsy. In conclusion, the findings of this study lend pharmacological credence to the suggested folkloric, ethnomedical uses of Rhus chirindensis in the management of childhood convulsions and epilepsy in some rural communities of South Africa.

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

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    Kavita Gahlot

    2013-01-01

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

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

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    Suneel Kumar Reddy

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-01-17

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

  5. 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

    transporter-1 (GAT-1), GAT-2, -3 or -4. It was found that 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridin-3-ol (THPO) and 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) displayed some inhibitory activity on GAT-1 and GAT-2, where the compounds exhibited a slightly lower potency on GAT-2 compared to GAT-1...... 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....

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

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    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  11. Anticonvulsant 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.

  12. 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

  13. Fucosterol, a sterol extracted from Sargassum fusiforme, shows antidepressant and anticonvulsant effects.

    Science.gov (United States)

    Zhen, Xing-Hua; Quan, Ying-Chun; Jiang, Hai-Ying; Wen, Zheng-Shun; Qu, You-Le; Guan, Li-Ping

    2015-12-01

    We previously showed that extracts of Sargassum fusiforme significantly reduce immobility time in the forced swim test and tail suspension test, suggesting that these extracts possess antidepressant-like effects. Here, fucosterol extracted from S. fusiforme was evaluated for antidepressant and anticonvulsant activities in mice. Fucosterol (10, 20, 30 and 40mg/kg) significantly shortened immobility time in the forced swim test and tail suspension test for30min after treatment but had no effect on locomotor activity in the open field test. Fucosterol significantly increased serotonin, norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of fucosterol may be mediated through these neurotransmitters. As assessed using maximal electroshock, fucosterol (20, 40, 100mg/kg) possessed anticonvulsant activity, whereas rotarod toxicity test results indicated that fucosterol did not induce neurotoxicity at the same dose levels in mice. Thus, fucosterol may be a useful antidepressant adjunct candidate for treating depression in patients with epilepsy. A significant increase in hippocampal brain-derived neurotrophic factor (BDNF) levels was found in the fucosterol 20mg/kg group (P<0.05). Our findings suggested that fucosterol may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels. PMID:26515446

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

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    Gulab S Shinde

    2013-01-01

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

  15. 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)

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    E R De Almeida

    2009-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Asmatanzeem Bepari

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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 .

  1. 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.

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.

    Science.gov (United States)

    Ghandourah, Hasan; Bhandal, Samarjeet; Brundler, Marie-Anne; Noseworthy, Mary

    2016-01-01

    A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. PMID:26825933

  6. Design and synthesis of 3,5-diarylpiperidin-2,6-diones as anticonvulsant agents.

    Science.gov (United States)

    Babu, Mariappan; Pitchumani, Kasi; Ramesh, Penugonda

    2012-01-15

    The present Letter describes a one-pot multi-component method that allows the efficient and mild preparation of 3,5-diphenylpiperidin-2,6-dione and a new series of 3,5-diarylpiperidin-2,6-dione derivatives from ethyl 2-arylacetates, formaldehyde and ammonia/aliphatic/aromatic amines. The structures of the compounds were elucidated by IR, NMR spectroscopic data and microanalyses. The anticonvulsant activities of these compounds were evaluated by maximal electroshock seizure test and were also evaluated for motor impairment. Among the synthesized compounds, 5a, 5b, 5d, and 5e could be considered potentially the most useful and safe therapeutic compound and 5g, 5i, 5j, 5m, and 5o exhibit potent activities. PMID:22189139

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Yusuf M

    2012-08-01

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

  9. 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...

  10. 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 ...

  11. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  14. 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 < 0.05) delayed the onset and prolonged the duration of convulsions in PTX, SCN, INZ, PTZ and NMDA-induced seizures. However, the anticonvulsant activity of the ethanolic extract of Ficus sur was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist), cyproheptadine (5-HT2 receptor antagonist) and L-NNA (nitric oxide synthase inhibitor) in picrotoxin-induced convulsion. The data obtained suggest that ethanol extract of Ficus sur possessed significant anticonvulsant effect, thereby confirming the traditional uses of Ficus sur in the treatment of epilepsies; mechanisms of which could involve interaction with GABAergic, glycinergic, serotonergic and glutaminergic system barks.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  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. 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.

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

    Science.gov (United States)

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

    2013-09-01

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

  2. 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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    The actions of the anticonvulsant gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin] have been somewhat enigmatic until recently, when it was claimed to be a gamma-aminobutyric acid-B (GABA(B)) receptor agonist acting exclusively at a heterodimeric complex containing the GABA(B(1a......)) splice variant (Mol Pharmacol 2001;59:144-152). In this study, we have investigated the effects of gabapentin on recombinant GABA(B(1a)) and GABA(B(1b)) receptors coexpressed with GABA(B(2)) in five different functional recombinant assays, its ability to inhibit [(3)H]GABA binding in a GABA(B) receptor......-selective binding assay using rat synaptic membranes, and its ability to inhibit transient lower esophageal sphincter relaxations in Labrador retriever dogs. Up to a concentration of 1 mM, gabapentin displayed no agonistic effects on either the GABA(B(1a,2)) or the GABA(B(1b,2)) heterodimer, when these were...

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

    Science.gov (United States)

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

    2015-01-01

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

  6. 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

  7. Evaluation of possible antioxidant and anticonvulsant effects of the ethyl acetate fraction from Platonia insignis Mart. (Bacuri) on epilepsy models.

    Science.gov (United States)

    Júnior, Joaquim Soares da Costa; de Almeida, Antonia Amanda C; Tomé, Adriana da Rocha; Citó, Antonia Maria das Graças Lopes; Saffi, Jenifer; de Freitas, Rivelilson Mendes

    2011-12-01

    The aim of present study was to examine the effects of the ethyl acetate fraction (EAF) from Platonia insignis on lipid peroxidation level, nitrite formation, and superoxide dismutase and catalase activities in rat striatum prior to pilocarpine-induced seizures as well as to explore its anticonvulsant activity in adult rats prior to pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures. Wistar rats were treated with vehicle, atropine (25mg/kg), EAF (0.1, 1, and 10mg/kg), pilocarpine (400mg/kg, P400 group), PTZ (60 mg/kg, PTZ group), PIC (8 mg/kg, PIC group), atropine+P400, EAF+P400, EAF+PTZ, or EAF+PIC. Significant decreases in number of crossings and rearings were observed in the P400 group. The EAF 10+P400 group also had significant increases in these parameters. In addition, in rats treated with P400, there were significant increases in lipid peroxidation and nitrite levels; however, there were no alterations in SOD and catalase activities. In the EAF 10+P400 group, lipid peroxidation and nitrite levels significantly decreased and SOD and catalase activities significantly increased after pilocarpine-induced seizures. Additionally, effects of the EAF were evaluated in PTZ and PIC models. EAF did not increase the latency to development of convulsions induced with PTZ and PIC at the doses tested. Our findings strongly support the hypothesis that EAF does not have anticonvulsant activity in the different models of epilepsy studied. Our results indicate that in the in vivo model of pilocarpine-induced seizures, EAF has antioxidant activity, but not anticonvulsant properties at the doses tested.

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

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. OBJECTIVES: The aim...... of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy. METHODS: This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000mg/day versus placebo (6-week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than...

  13. 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.

  14. 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

  15. Bone mineral density, vitamin D and anticonvulsant therapy Densidade mineral óssea, vitamina D e terapia anticonvulsivante

    Directory of Open Access Journals (Sweden)

    SILVANA FILARDI

    2000-09-01

    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.O objetivo deste estudo foi avaliar a densidade mineral óssea e o metabolismo da vitamina D em usuários crônicos de anticonvulsivantes. MÉTODOS: Foram estudados 69 pacientes ambulatoriais, masculinos, usuários crônicos de anticonvulsivantes por período mínimo de 5 anos e comparados a 30 controles normais. Foram efetuadas as medidas da densidade mineral óssea e dos níveis plasmáticos do cálcio, cálcio iônico, fosfatase alcalina, paratormônio, 25-hidroxi-colecalciferol e 1,25-di-hidroxi-colecalciferol. RESULTADOS: Nenhuma diferença na densidade mineral óssea e nos níveis plasmáticos da vitamina D e paratormônio foram observadas entre os pacientes e os controles. A densidade mineral óssea não se mostrou associada ao uso crônico de anticonvulsivantes. CONCLUSÕES: Pacientes adultos, do sexo masculino, usuários crônicos de anticonvulsivantes, residentes em regiões ensolaradas, têm densidade mineral óssea e níveis plasmáticos de vitamina D normais.

  16. Selective GABA transporter inhibitors tiagabine and EF1502 exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABA(A) receptor agonist gaboxadol

    DEFF Research Database (Denmark)

    Madsen, Karsten Kirkegaard; Ebert, Bjarke; Clausen, Rasmus Prætorius;

    2011-01-01

    on GABA(A) receptors, inhibits both GAT1 and the extrasynaptic GABA and betaine transporter BGT1, and exerts a synergistic anticonvulsant effect when tested in combination with tiagabine. In the present study, the anticonvulsant activity and motor impairment associated with systemic administration...

  17. Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L.) Sw., Fabaceae, leaves Efeito anticonvulsivante do extrato etanólico das folhas de Caesalpinia pulcherrima (L.) Sw., Fabaceae

    OpenAIRE

    Dinesh Kumar; Jitender Singh; Anupama Baghotia; Sunil Kumar

    2010-01-01

    In this study, ethanol extract of Caesalpinia pulcherrima (L.) Sw., Fabaceae, leaves (CPEE) was investigated for anticonvulsant effect against maximal electroshock (MES) and pentylenetetrazole (PTZ) induced seizures in rats and mice at dose levels 200 and 400 mg/kg, i.p. respectively. Diazepam (3 mg/kg, i.p.) was used as a standard anticonvulsant drug for comparison. CPEE was found to be safe up to the dose of 4000 mg/kg in mice, when administered intraperitoneally. The extract at 400 mg/kg d...

  18. Solid-state forms of sodium valproate, active component of the anticonvulsant drug epilim.

    Science.gov (United States)

    Petrusevski, Gjorgi; Naumov, Pance; Jovanovski, Gligor; Bogoeva-Gaceva, Gordana; Ng, Seik Weng

    2008-09-01

    The results of the first detailed and systematic investigation of the solid-state forms of sodium valproate, one of the most potent and widely used anticonvulsant medicines, are presented. By using wet and dry methods, eight solid forms of varying stability in air were obtained and characterized. Three extremely hygroscopic polycrystalline hydrates, Na(C8H15O2) X H2O (form A), Na(C8H15O2) X xH2O (form B), and Na(C8H15O2) X yH2O (form D), three acid-stabilized stoichiometric solvates, Na3(C8H15O2)3(C8H16O2)H2O (form C), Na(C8H15O2)(C8H16O2) (form E), and Na3(C8H15O2)3(C8H16O2) X 2H2O (form F), the pure anhydrous salt Na(C8H15O2) (form H), and an additional unstable thermal intermediate Na3(C8H15O2)3(C8H16O2)0.5 (form G) were prepared. Under ambient conditions, forms A and B as well as the commercially available compound appear as very hygroscopic white powders. Form C is less hygroscopic, while forms E and F are stable and are not hygroscopic. Partial stabilization of forms A and B can be achieved by evacuation and pressing, which results in a lower hydrate D, or after a heating-cooling cycle, resulting in crystallization of the anhydrous salt H. Addition of one molecule of valproic acid and saturation with one molecule of water of forms A and B results in the less hygroscopic form C. Addition to form C of a second water molecule affords form F, which is not hygroscopic and is indefinitely stable. The symmetric structure and medium alkyl chain length of the valproate ion are some of the probable reasons for the presence of a number of solid solvates: in its most stable conformation, the valproate ion cannot simultaneously pack efficiently and interact strongly through the negatively charged carboxylate group without leaving voids in the crystalline lattice. The conformational flexibility of the aliphatic chains probably aids the penetration of water molecules, which results in a strong affinity for the absorption of water. PMID:18613204

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

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    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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    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.

  2. 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

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

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    Pravin O. Patil

    2016-07-01

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

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

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    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.

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

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

    2007-09-01

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

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

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    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

  7. 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

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

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    Ferraro Giuseppe

    2007-07-01

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

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

    Science.gov (United States)

    Showraki, Alireza; Emamghoreishi, Masoumeh; Oftadegan, Somayeh

    2016-01-01

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

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

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    Alireza Showraki

    2016-05-01

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

  11. 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.

  12. 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

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

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    Luís André Castro

    2006-01-01

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

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

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    Justin Wang

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

  15. 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

  16. Anticonvulsant and Neurotoxicity of Some Novel 1-([1,3,4]thiadiazino[6,5- b]indol-3-yl Semicarbazides.

    Science.gov (United States)

    Deshmukh, Ravitas; Thakur, Alok S; Jha, Arvind K; Kumar, Sudhir P

    2015-01-01

    In the present study a series of new N(4)-(4-substituted benzylidene)-N(1)-([1,3,4]thiadiazino [6,5-b]indol-3-yl)semicarbazide (1-6), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-(1-(4-substituted phenyl)ethylidene)semicarbazide (7-10), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-((4-substituted phenyl)(phenyl)methylene) semicarbazide. (11-14) have been synthesized from isatin and thiosemicarbazide through multiple steps to meet structural necessities for the anticonvulsant activity. All the newly prepared compounds were characterized by spectral techniques like FT-IR, (1)H and (13)C NMR, EI-MS and elemental analysis. All the newly synthesized compounds were investigated for the anticonvulsant activity against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) models and their neurotoxicity were also evaluated by rotarod test. The results obtained showed that 64% of the compounds showed protection in the MES test and 36% of the compounds showed protection in ScPTZ test. Some of the compounds also showed good activity after oral administration. Among the synthesized compounds, compound 14 was shown to be the most active compound showing activity at 100 and 300 mg/kg in MES and ScPTZ test with prolonged duration of action. In the present study, semicarbazones of hydroxy containing carbonyl compounds were depicted to be the potent molecule with low neurotoxicity and prolong duration of action on oral administration. The result of the present study may be used for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity. PMID:26100150

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  18. 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

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

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    Rita Citraro

    2016-09-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  2. 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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Emmanuel Randrianarivo; Filippo Maggi; Marcello Nicoletti; Philippe Rasoanaivo

    2016-01-01

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

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

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    S Namvar Aghdash

    2015-11-01

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

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

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    Yun-Hong Yu

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

  7. 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

  8. ANTI-CONVULSANT ACTIVITY OF GANAXOLONE ALONE A ND IN COMPARISON WITH STANDARD ANTI-EPILEPTIC DRUGS IN RODENT MODELS

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    Subhani Basha

    2012-08-01

    Full Text Available ABSTRACT: BACKGROUND: Presently, treatment of epilepsy with standa rd anti-epileptic drugs is associated with a number of shortcomings invi ting us to study newer agents that would overcome these problems or search for the dr ugs or substances, which would enhance the efficacy or reduce the dose or toxicity of these standard anti-epileptic drugs. Ganaxolone (GNX (3α-hydroxy-3β-methyl-5α-pregnan-20-one, a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive a llosteric modulator of GABA A receptors, may represent a new treatment approach for epilep sy. AIM: To evaluate the effect of Ganaxolone on maximal electroshock (MES induced and Pen tylenetetrazol (PTZ induced convulsions and also their effect in combination with co nventional antiepileptic drugs (CAEDs. MATERIAL AND METHODS: Wister strain albino rats weighing 200-250 gm were used. Effects of Ganaxolone (5 &10 mg/kg alone and in combination with standard drugs were studied in MES and PTZ induced seizure model s. Abolition of tonic hind limb extension was an index of anticonvulsant activity in MES, while for PTZ seizures; failure to observe c lonus for 5sec duration for 30min was the index. F ollowing that, percentage inhibition was calculated. STATISTICS: ANOVA followed by Newman-Keuls Multiple Compar ison Test was used for analysis of data between the groups . RESULTS : In MES seizures, significant anti- epileptic activity was observed with 10mg of Ganaxolone compared to control group but has less activity when compared to that of P henobarbitone. In PTZ induced convulsions, the anti-epileptic effect of Sodium Valproate was h igher than Ganaxolone, but both were statistically significant as compared to contr ol. In PTZ-induced seizures, augmented effect s were obtained when Ganaxolone was combined wi th sodium valproate i.e. 55%. CONCLUSIONS: The results provide a lead for potential benefit of adding Ganaxolone to Sodium Valproate in the treatment of epilepsy

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

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    Ricardo Alberto Moreno

    2004-10-01

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

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

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    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.

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

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    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.

  12. 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

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

    Science.gov (United States)

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

    2012-03-01

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

  14. 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.

  15. 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

  16. 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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. 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

  20. Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L. Sw., Fabaceae, leaves Efeito anticonvulsivante do extrato etanólico das folhas de Caesalpinia pulcherrima (L. Sw., Fabaceae

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar

    2010-11-01

    Full Text Available In this study, ethanol extract of Caesalpinia pulcherrima (L. Sw., Fabaceae, leaves (CPEE was investigated for anticonvulsant effect against maximal electroshock (MES and pentylenetetrazole (PTZ induced seizures in rats and mice at dose levels 200 and 400 mg/kg, i.p. respectively. Diazepam (3 mg/kg, i.p. was used as a standard anticonvulsant drug for comparison. CPEE was found to be safe up to the dose of 4000 mg/kg in mice, when administered intraperitoneally. The extract at 400 mg/kg dose produced significant (pNeste estudo, foi investigada o efeito anticonvulsivante do extrato etanólico das folhas de Caesalpinia pulcherrima (L. Sw., Fabaceae (CPEE, utilizando convulsões induzidas por eletrochoque máximo (MES e pentilenetetrazol (PTZ, em ratos e camundongos, nas doses 200 e 400 mg/kg, i.p., respectivamente. Diazepam (3 mg/kg, i.p. foi usado como uma droga anticonvulsivante padrão. O extrato (CPEE foi seguro até a dose de 4000 mg/kg em camundongos, quando administrado por via intraperitoneal. O extrato de 400 mg/kg produziu efeito anticonvulsivante contra induções por PTZ de forma significativa (p<0,01. Em modelo de convulsão induzida por MES, não houve alterações significativas no início, bem como a duração das crises de extensão dos membros pélvicos em relação ao controle na dose de 200 mg/kg quando administrada por via intraperitoneal. No entanto, o extrato (CPEE, 400 mg/kg i.p., de forma significativa (p<0,01, atrasou o início, como também diminuiu a duração das crises de extensão dos membros posteriores (HLES em relação ao controle. O extrato (CPEE aumentou a percentagem de proteção dos animais em dose maior (200 mg/kg em ambos os modelos. Os resultados do estudo sugerem que o extrato etanólico de folhas de Caesalpinia pulcherrima (L. Sw. possui efeito anticonvulsivante.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-15

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

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

    Directory of Open Access Journals (Sweden)

    Vicente Vera

    2015-12-01

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

  3. Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice

    Directory of Open Access Journals (Sweden)

    Ranjana I Brahmane

    2010-01-01

    Full Text Available Objective: To study the effect of calcium channel blockers (CCBs cinnarizine and nifedipine on maximal electroshock (MES-induced and pentylenetetrazole (PTZ-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED. Materials and Methods: For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg, nifedipine (5 mg/kg, sodium valproate (300 mg/kg and carbamazepine (8 mg/kg alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher′s exact test (Ovvind Langsrud software, German version. Results: In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures. Conclusion: The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.

  4. 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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  7. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. 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

  10. Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones

    Directory of Open Access Journals (Sweden)

    Mohamed N. Aboul-Enein

    2014-09-01

    Full Text Available Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x are reported. The intermediates 1-[(aryl(cyanomethylamino] cycloalkanecarboxamides (3a–f were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg and Ethosuximide (ED50 = 0.92 mmol/kg, respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.

  11. Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones

    Science.gov (United States)

    Aboul-Enein, Mohamed N.; El-Azzouny, Aida A.; Attia, Mohamed I.; Maklad, Yousreya A.; Aboutabl, Mona E.; Ragab, Fatma; El-Hamid, Walaa H. A. Abd

    2014-01-01

    Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones (6m–x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino]cycloalkanecarboxamides (3a–f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg) and Ethosuximide (ED50 = 0.92 mmol/kg), respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen. PMID:25250910

  12. 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

  13. 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.

  14. Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1) channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors and TRPV1 channels.

    Science.gov (United States)

    Vilela, Luciano R; Medeiros, Daniel C; de Oliveira, Antonio Carlos P; Moraes, Marcio F; Moreira, Fabricio A

    2014-10-01

    Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB1 receptors. Anandamide, however, also activates TRPV1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1 blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in inhibiting pentylenetetrazole (PTZ)-induced seizures in mice. We also investigated the contribution of CB1 activation and TRPV1 blockade to the overt effect of AA-5-HT. In the first experiment, injection of AA-5-HT (0.3-3.0 mg/kg) delayed the onset and reduced the duration of PTZ (60 mg)-induced seizures in mice. These effects were reversed by pre-treatment with the CB1 antagonist, AM251 (1.0-3.0 mg/kg). Finally, we observed that administration of the selective TRPV1 antagonist, SB366791 (0.1-1 mg/kg), did not entirely mimic AA-5-HT effects. In conclusion, AA-5-HT alleviates seizures in mice, an effect inhibited by CB1 antagonism, but not completely mimicked by TRPV1 blockage, indicating that the overall effect of AA-5-HT seems to depend mainly on CB1 receptors. This may represent a new strategy for the development of drugs against seizures, epilepsies and related syndromes.

  15. Evaluation of Anticonvulsant, Antidepressant-, and Anxiolytic-like Effects of an Aqueous Extract from Cultured Mycelia of the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Higher Basidiomycetes) in Mice.

    Science.gov (United States)

    Socala, Katarzyna; Nieoczym, Dorota; Grzywnowicz, Krzysztof; Stefaniuk, Dawid; Wlaz, Piotr

    2015-01-01

    Ganoderma lucidum is a well-known medicinal mushroom with a long history of use. This study was designed to assess the anticonvulsant potential of an aqueous extract from cultured G. lucidum mycelium in 3 acute seizure models: timed intravenous pentylenetetrazole infusion, maximal electroshock seizure threshold, and 6-Hz-induced psychomotor seizure tests in mice. Moreover, antidepressant-like and anxiolytic-like effects of G. lucidum were evaluated using the forced swim test and the elevated plus maze test in mice, respectively. No changes in seizure thresholds in the intravenous pentylenetetrazole and maximal electroshock seizure threshold tests after acute treatment with G. lucidum extract (200-600 mg/kg) was observed. However, the studied extract (100-400 mg/kg) significantly increased the threshold for psychomotor seizures in the 6-Hz seizure test. In the forced swim test, G. lucidum (100-400 mg/kg) significantly reduced the duration of immobility. No anxiolytic-like or sedative effects were reported in mice pretreated with the extract (400-600 mg/kg). G. lucidum extract (50-2400 mg/kg) did not produce toxic effects in the chimney test (motor coordination) or grip-strength test (neuromuscular strength). Further studies are required to explain the neuropharmacological effects of G. lucidum and to identify its active ingredients that may affect seizure threshold, mood, or anxiety.

  16. 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.

  17. Sedative, hypnotic and anticonvulsive effects of an adenosine analogue WS090501%腺苷类似物WS090501的镇静、催眠和抗惊厥作用

    Institute of Scientific and Technical Information of China (English)

    李伟; 张建军

    2011-01-01

    This study is to examine the sedative, hypnotic and anticonvulsive effects of an adenosine analogue, WS090501. The spontaneous locomotor activity was recorded by open field equipment, and the EEG of rats was recorded by polyphysiograph. Pentylenetetrazol (PTZ)-induced seizure model was used. The spontaneous locomotor activity was decreased by WS090501 at various doses (0.06, 0.13, and 0.25 mg·kg-1), and the decreasing rate was 28.4%, 47.1% and 61.2% respectively. Furthermore, the effect of WS090501 on spontaneous locomotor activity of mice can be antagonized by DPCPX, a selective adenosine A1R antagonist, but cannot be antagonized by SCH58261, a selective adenosine A2AR antagonist. The NREM sleep was significantly increased by WS090501 (0.05 and 0.2 mg·kg-1), and the increasing rate was 27.6% and 102.8%, respectively, at 6th hour after administration. The REM sleep decreased significantly at the higher dose. PTZ induced serious convulsion in mice. The latency of convulsion was prolonged, and the number of seizure and mortality decreased after administration of WS090501. These results show that WS090501 has potent sedative, hypnotic and anticonwlsive effects, which may be mediated through adenosine A1R.%@@ 腺苷是一种内源性的嘌呤核苷,具有广泛的生理性调节作用.腺苷类似物具有显著的镇静、催眠和抗惊厥作用,可以抑制啮齿类动物的自主活动、诱导NREM睡眠(non rapid-eye-movement sleep,非快动眼睡眠).腺苷及其类似物通过腺苷受体发挥作用.

  18. N,N'-dicyclohexylsulfamide and N,N'-diphenethylsulfamide are anticonvulsant sulfamides with affinity for the benzodiazepine binding site of the GABA(A) receptor and anxiolytic activity in mice.

    Science.gov (United States)

    Wasowski, Cristina; Gavernet, Luciana; Barrios, Ivana A; Villalba, Maria L; Pastore, Valentina; Samaja, Gisela; Enrique, Andrea; Bruno-Blanch, Luis E; Marder, Mariel

    2012-01-15

    A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-diphenethylsulfamide (10), competitively inhibited the binding of [(3)H]-flunitrazepam to the benzodiazepine binding site with K(i)±SEM values of 27.7±4.5μM (n=3) and 6.0±1.2μM (n=3), respectively. The behavioral actions of these sulfamides, i.p. administered in mice, were examined in the plus-maze, hole-board and locomotor activity assays. Compound 7 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the hole-board test (at 1 and 3mg/kg) and the plus-maze assay (at 1 and 3mg/kg). Compound 10 evidenced anxiolytic activity in the plus-maze and the hole-board tests at 1mg/kg. Locomotor activity of mice was not modified by compound 7 or 10 at the doses tested. Flumazenil, a non selective benzodiazepine binding site antagonist, was able to completely reverse the anxiolytic-like effects of these sulfamides, proving that the GABA(A) receptor is implicated in this action. Anxiety represents a major problem for people with epilepsy. The use of anxiolytic and anticonvulsant sulfamides would be beneficial to individuals who suffer from both disorders. PMID:22056620

  19. 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].

  20. Ausências mioclônicas: estudo comparativo da potência anticonvulsivante do nitrazepam (Mogadon e do diazepam (Valium Myoclonic absences: a comparative study of the anticonvulsant potency of nitrazepan and diazepam

    Directory of Open Access Journals (Sweden)

    Michel Pierre Lison

    1969-09-01

    Full Text Available Foi comparada a potência anticonvulsivamente do nitrazepam, do diazepam e da trimetadiona em 5 pacientes com ausências mioclônicas. Os doentes receberam, além das medicações anticonculsivantes, um placebo. O teste terapêutico foi constituído por tratamentos sucessivos de 4 dias, planejados com o fim de se eliminar os possíveis efeitos residuais de uma droga sobre a outra, administrada ulteriormente. Na análise dos resultados, a comparação das médias individuais dos diversos tratamentos foi baseada no teste de Tukey. Em dois casos não houve necessidade de análise estatística para demonstrar a superioridade do nitrazepam e do diazepam sobre os demais produtos utilizados; em outros dois, a aplicação do teste de Tukey levou à mesma conclusão. No quinto caso as flutuações do número de ausências mioclônicas durante o ensaio terapêutico sugerem comportamento semelhante, embora a análise estatística individual não revele diferenças significativas. Há indícios de que o nitrazepam tem ação superior ao diazepam sobre esse tipo de crise convulsiva. A trimetadiona revelou-se superior ao placebo, porém inferior ao nitrazepam e ao diazepam. O principal inconveniente do nitrazepam e do diazepam é o de precipitar crises generalizadas tônico-clônicas.The anticonvulsant potency of nitrazepan, diazepan and trimetadiones in five patients with myoclonic absences was compared. A placebo was also used. Therapeutic tests were performed by 4-days successive treatments designed to avoid the residual effects of one drug upon the other administered afterwards. In two cases statistical analysis was not necessary for demonstration of the superiority of nitrazepan and diazepan in regard to trimetadiones; in two others the application of Tukey's test allowed this same conclusion. In the last case the numeric variations of the seizures during the therapeutic essay suggest identical conclusion allthough the statistical analysis was not

  1. Anticonvulsant-induced downbeat nystagmus in epilepsy

    Science.gov (United States)

    Wu, Dongyan; Thijs, Roland D.

    2015-01-01

    We report data from two patients who developed reversible downbeat nystagmus (DBN) while using AEDs within the therapeutic range. All previous reported cases of epilepsy with drug-induced DBN related to toxic levels of AEDs were summarized, and DBN was found mostly occurring in those using a sodium channel blocking AED. We propose that in our cases, the DBN with therapeutic AED levels may be explained by additive effects of sodium channel blockers. Adverse drug effects should be considered as a cause of DBN in people with epilepsy treated with multiple AEDs. PMID:26543808

  2. Anticonvulsant-induced downbeat nystagmus in epilepsy

    Directory of Open Access Journals (Sweden)

    Dongyan Wu

    2015-01-01

    Full Text Available We report data from two patients who developed reversible downbeat nystagmus (DBN while using AEDs within the therapeutic range. All previous reported cases of epilepsy with drug-induced DBN related to toxic levels of AEDs were summarized, and DBN was found mostly occurring in those using a sodium channel blocking AED. We propose that in our cases, the DBN with therapeutic AED levels may be explained by additive effects of sodium channel blockers. Adverse drug effects should be considered as a cause of DBN in people with epilepsy treated with multiple AEDs.

  3. 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 ...

  4. 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

  5. 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

  6. 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

  7. 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...

  8. 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.

  9. Anticonvulsant therapy in brain-tumor related epilepsy

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    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.

  10. 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

  11. 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 ...

  12. 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...

  13. 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

  14. 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...

  15. 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

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

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    Musa Mumammad Aliyu

    2014-04-01

    Conclusions: These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Damasceno, D.D. [Departamento de Desenvolvimento Educacional,Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais, Barbacena, MG (Brazil); Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doretto, M.C.; Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-07-20

    Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.

  18. 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, ...

  19. 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 ...

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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 ...

  5. 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.

  6. 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.

  7. The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan.

    Directory of Open Access Journals (Sweden)

    James J Collins

    2008-10-01

    Full Text Available Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals.

  8. 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

  9. Predicting parental anticonvulsant medication compliance using the theory of reasoned action.

    Science.gov (United States)

    Austin, J K

    1989-04-01

    One approach to better understanding compliance behavior is the use of the theory of reasoned action. In this article, the theory of reasoned action is used to predict the compliance behavior of 29 parents of children with epilespy. In support of the theory, behavioral intention was found to significantly predict (p less than 0.01) parental medicine-giving behavior. Contrary to the results predicted by the theory, parents' attitudes toward giving the medication correlated with a significant amount of variance in medicine-giving behavior beyond that accounted for by behavioral intention.

  10. [The role of the substantia nigra in the anticonvulsive and antiaggressive effects of diazepam during pharmacological kindling].

    Science.gov (United States)

    Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Makul'kin, R F

    1990-01-01

    The seizure activity was investigated on the model of pharmacological kindling which was induced by repeated picrotoxin injections in the subthreshold dose, after the tryptic fragment of T5 protein-human diazepam binding inhibitor (DBI) (10 micrograms) injection into a reticular part of substantia nigra. An increase in the seizure reaction and suppression of the antiseizure diazepam action were observed. Intranigral DBI injection induced no change in a threshold of "attacks" in rats which were induced through electric shocks delivered to animals with an electrode floor and no changes in antiaggressive diazepam action were observed under such conditions.

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

    Directory of Open Access Journals (Sweden)

    Emmanuel Randrianarivo

    2016-06-01

    Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.

  12. 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...

  13. Crystal structure of 1,3-dimethyl-3-phenylpyrrolidine-2,5-dione: a clinically used anticonvulsant

    Directory of Open Access Journals (Sweden)

    Carlos Ordonez

    2014-09-01

    Full Text Available In the title compound, C12H13NO2, the five-membered ring has an envelope conformation; the disubstituted C atom lies out of the mean plane through the four other ring atoms (r.m.s. deviation = 0.0038 Å by 0.1877 (18 Å. The plane of the phenyl substituent is practically perpendicular to that of the planar part of the five-membered ring, with a dihedral angle of 87.01 (5°. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming inversion dimers. The dimers are linked by further C—H...O hydrogen bonds, as well as carbonyl–carbonyl attractive interactions [O...C = 3.2879 (19 Å], forming a three-dimensional framework structure.

  14. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; de Jong, Esther; de la Fonteyne, Liset J. J.; de Klerk, Arja; Piersma, Aldert H.

    2015-01-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecu

  15. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol.

    Science.gov (United States)

    Schulpen, Sjors H W; de Jong, Esther; de la Fonteyne, Liset J J; de Klerk, Arja; Piersma, Aldert H

    2015-04-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecular interaction of compounds with the neural differentiation process. Within the 11-day differentiation protocol of the assay, embryonic stem cells lost their pluripotency, evidenced by the reduced expression of stem cell markers Pou5F1 and Nanog. Moreover, stem cells differentiated into neural cells, with morphologically visible neural structures together with increased expression of neural differentiation-related genes such as βIII-tubulin, Map2, Neurogin1, Mapt and Reelin. Valproic acid (VPA) and carbamazepine (CBZ) exposure during hESTn differentiation led to concentration-dependent reduced expression of βIII-tubulin, Neurogin1 and Reelin. In parallel VPA caused an increased gene expression of Map2 and Mapt which is possibly related to the neural protective effect of VPA. These findings illustrate the added value of gene expression analysis for detecting compound specific effects in hESTn. Our findings were in line with and could explain effects observed in animal studies. This study demonstrates the potential of this assay protocol for mechanistic analysis of specific compound-induced inhibition of human neural cell differentiation.

  16. 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

  17. 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 ...

  18. Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress.

    Science.gov (United States)

    Tawfik, Mona K

    2011-12-01

    Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.

  19. The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. V. Lack of seasonal influences on amygdala kindling in rats.

    Science.gov (United States)

    Wlaź, P; Löscher, W

    1993-10-01

    Previous studies have suggested that seizure models may be affected by seasonal rhythms, even under controlled environmental conditions. In the present experiments in rats with chronically implanted electrodes in the basolateral amygdala, kindling was initiated at different seasons of the year over a period of 3 years. In a total of 109 animals, the following parameters were determined: the threshold for induction of amygdaloid afterdischarges prior to kindling (pre-kindling ADT), the number of daily amygdaloid stimulations to fully kindled (stage 5) seizures, and the post-kindling ADT. No seasonal influences were found with respect to rate of kindling development and post-kindling ADT. In contrast, pre-kindling ADTs appeared to be higher in spring than in other seasons, which, however, could not be reproduced in another spring. Thus, the data do not indicate that seasonal rhythms affect the kindling model of epilepsy.

  20. [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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1) is NO an...

  2. 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...

  3. The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review.

    Science.gov (United States)

    Dols, Annemiek; Sienaert, Pascal; van Gerven, Heleen; Schouws, Sigfried; Stevens, Anja; Kupka, Ralph; Stek, Max L

    2013-11-01

    Side effects are among the most frequent reasons preventing patients from taking their medication. Although the management of side effects is an important issue in clinical practice, particularly in patients with physical comorbidities, research on clinical management of side effects is rather scattered. The aim of this article was to provide an overview on the prevalence and management of various side effects of mood-stabilizing drugs. In December 2012, we carried out a PubMed search for publications reporting side effects in patients with bipolar disorder. Naturalistic studies describing the prevalence of side effects in treatment with mood stabilizers are sparse. We describe the prevalence of neurological, gastrointestinal, metabolic, thyroid, dermatological, nephrogenic, cognitive, sexual, hematological, hepatogenic, and teratogenic side effects of lithium, valproate, carbamazepine, and lamotrigine and discuss their clinical management. There are specific strategies that aim at reducing side effects, but, to date, studies on the efficacy of these interventions are lacking. With age, the renal elimination and hepatic metabolism of drugs reduce and comedication and somatic comorbidity increase, making elderly patients particularly susceptible to side effects. Most side effects can be managed by striving for the lowest possible dose without losing efficacy by lowering the dose below the therapeutic window. Specific measurements to limit certain side effects are available and may ameliorate treatment adherence.

  4. Epilepsy - children

    Science.gov (United States)

    Seizure disorder - children; Convulsion - childhood epilepsy; Medically refractory childhood epilepsy; Anticonvulsant - childhood epilepsy; Antiepileptic drug - childhood epilepsy; AED - childhood epilepsy

  5. 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...

  6. 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.

  7. 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...

  8. 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.

  9. 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

  10. 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.

  11. Anticonvulsiva bij agressie, angststoornissen, psychotische stoornissen en alcohol- en cocaïneonttrekkingsverschijnselen

    NARCIS (Netherlands)

    Barth-Van Veldhuizen, H.G.J.; Reinders, C.; Loonen, A.J.M.; Nolen, W.A.

    2003-01-01

    BACKGROUND: There is an increasing interest in the treatment of psychiatric symptoms with anticonvulsants, especially in the treatment of refractory patients. It is questionable whether or not the efficacy of anticonvulsants as psychotropic drugs is sufficiently verified. AIM: To examine the efficac

  12. Tiagabine in treatment refractory bipolar disorder : a clinical case series

    NARCIS (Netherlands)

    Suppes, T; Chisholm, KA; Dhavale, D; Frye, MA; Atshuler, LL; McElroy, SL; Keck, PE; Nolen, WA; Kupka, R; Denicoff, KD; Leverich, GS; Rush, AJ; Post, RM

    2002-01-01

    Objectives: Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the gamma-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant

  13. 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.

  14. 加巴喷丁胶囊治疗疱疹后神经痛的多中心临床观察%A multicenter, randomized, double-blind, placebo-controlled, parallel design study on the efficacy and safety of gabapentin, an anticonvulsant drug in the treatment of postherpetic neuralgia

    Institute of Scientific and Technical Information of China (English)

    顾菊林; 温海; 刘训荃; 郑志忠; 顾军; 于浩

    2009-01-01

    目的 观察加巴喷丁治疗疱疹后神经痛的临床疗效和安全性.方法 多中心、随机双盲、安慰剂对照、平行设计临床试验.疱疹后神经痛患者随机分为治疗组和对照组,两组患者分别口服加巴喷丁胶囊1800 mg/d或安慰剂胶囊,总共接受6周的药物治疗.于治疗前及治疗后第1、3、6周各随访1次,进行疗效和安全性评价.以视觉模拟评分法进行疱疹后神经痛的疼痛评分作为主要观察指标,以5点严重程度评分方法进行睡眠质量评分作为次要观察指标.结果 4个中心共人选141例疱疹后神经痛患者,125例完成试验,其中试验组66例,对照组59例.与用药前相比,用药后1周、3周和6周时,两组在疼痛严重程度、睡眠质量方面均有不同程度改善;试验组在用药后1周、3周改善更为明显.用药后第1周和第3周试验组的有效率分别为29.58%和57.75%,对照组分别为13.04%和40.58%,试验组高于对照组,两组比较,差异均有统计学意义(X2CMH分别为5.94,4.12,P<0.05).加巴喷丁有较好的耐受性,不良反应主要表现为头晕、头昏、嗜睡和转氨酶升高等.结论 加巴喷丁胶囊治疗疱疹后神经痛,能改善患者疼痛严重程度和睡眠质量,不良反应发生率低.%Objective To observe the clinical efficacy and safety of gahapentin in the treatment of postherpetic neuralgia. Methods A multicenter, randomized, double-blind, placebo-controlled, parallel design, 6-week study was performed. Patients with postherpetic neuralgia were recruited into this study and randomly divided into two groups to receive gabapentin or placebo 1800 mg daily in three divided doses with a forced titration schedule, respectively. The primary efficacy measure was change in the pain score based on a visual analogue scale from baseline to the final week of therapy, and secondary measure was the improvement in sleep quality scored on a 5-point severity scale. Efficacy and safety evaluation was performed at baseline, and 1, 3, and 6 weeks atter the treatment. Results One hundred and forty-one patients were recruited in four clinical centers, and 125 patients completed the trial, of whom 66 were in the treatment group and 59 in the control group. An improvement was observed in both pain scores and sleep scores on week 1, 3 and 6 in both two groups, and the improvement was greater in gabapentin-treated group than that in the control group. The response rate was 29.58% and 57.75%, respectively in gabapentin-treated group on week 1 and 3, com-pared to 13.04% and 40.58%, respectively, in the control group (t = 5.94, 4.12, respectively, both P <0.05).Gabapentin was well tolerated, and the most common adverse events were dizziness, vertigo, somnolence and transient abnormality of hepatic function. Conclusion Gabapentin could markedly reduce pain intensity and improve sleep quality with a low incidence of adverse events in patients with postherpetic neuralgia.

  15. 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.

  16. 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 ...

  17. 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

  18. Zonisamide

    Science.gov (United States)

    ... called anticonvulsants. It works by decreasing abnormal electrical activity in the brain. ... mention any of the following: amiodarone (Cordarone, Pacerone);antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral); carbonic ...

  19. Drug: D02716 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ptics N03AX16 Pregabalin D02716 Pregabalin (JAN/USAN/INN) USP drug classification [BR:br08302] Anticonvulsants Calcium Channel Modify...ing Agents Pregabalin D02716 Pregabalin (JAN/USAN/INN) C

  20. 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 ...

  1. 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.

  2. 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.

  3. 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 ...

  4. [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

  5. [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.

  6. 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

  7. 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 ...

  8. 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

  9. 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

  10. 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, ...

  11. PRENATAL EXPOSURE TO PHENYTOIN, FACIAL DEVELOPMENT, AND A POSSIBLE ROLE FOR VITAMIN-K

    NARCIS (Netherlands)

    HOWE, AM; LIPSON, AH; SHEFFIELD, LJ; HAAN, EA; HALLIDAY, JL; JENSON, F; DAVID, DJ; WEBSTER, WS

    1995-01-01

    Ten patients with maxillonasal hypoplasia (Binder ''syndrome''), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate ca

  12. 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 ...

  13. Toxicity and Treatment of Pharmaceutical and Personal Care Products Using Exotic Plants - A Laboratory Scale Experiment

    DEFF Research Database (Denmark)

    Ramírez Vargas, Carlos Andrés; Paredes, Diego; Cubillos, Janneth;

    Pharmaceuticals and personal care products (PPCPs) detected in the environment belong to a large and diverse group of organic substances (analgesics, antibiotics, anticonvulsants, soaps, lotions, toothpaste, etc.). PPCPs reach aquatic ecosystems through point and diffuse discharges (unused/expired...

  14. Drug: D00538 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (6323) Dopaminergic synapse Enzyme: CYP3A4 [HSA:1576] map07033 Anticonvulsants map07057 Antiparkins...m 113 Antiepileptics 1139 Others D00538 Zonisamide (JAN/USAN/INN) 116 Antiparkinsonian agents 1169 Others D0

  15. 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.

  16. 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,...

  17. 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...

  18. Postoperative epilepsy in patients undergoing craniotomy for glioblastoma multiforme.

    Science.gov (United States)

    Telfeian, A E; Philips, M F; Crino, P B; Judy, K D

    2001-03-01

    Glioblastoma multiforme (GBM) has associated with it one of the poorest prognoses among brain tumors. Postoperative seizures and the side effects of anticonvulsants, routinely given for prophylactic purposes, add to patient morbidity. The primary goal of this study was to determine who, of those undergoing craniotomy for GBM resection, is at risk for epilepsy. We studied 72 consecutive patients who underwent craniotomy and palliative resection for GBM. Twenty-nine presented with seizures and 17 had postoperative seizures. All patients were treated with a postoperative anticonvulsant for at least six months; anticonvulsants were continued longer if there was a postoperative seizure. Patient factors examined for an association with risk for postoperative seizure included age, sex, tumor size, tumor location, adjuvant therapy, postoperative complications and history of preoperative seizures. The majority of patients with no prior seizure history and who seized postoperatively had their first seizure after withdrawal from their anticonvulsant medication. All, but one, of the patients with both pre- and postoperative seizures had their first postoperative seizure while still on anticonvulsants. Smaller tumor size and frontal resection were associated with an increased risk of postoperative seizures. Our data suggests that those who do not present with seizures and undergo GBM resection may still be prone to seize but more easily protected from postoperative seizures with anticonvulsant therapy than patients who present with seizures; resection of frontal tumors and smaller tumors seemed to indicate an increased risk for postoperative seizures. PMID:11370829

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  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

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os pacientes com paralisia cerebral (PC frequentemente usam fármacos para tratamento de doenças concomitantes, como convulsões. O midazolam é o hipnótico mais utilizado como medicação pré-anestésica e suas interações medicamentosas nos pacientes com PC são desconhecidas. O objetivo deste estudo foi avaliar o midazolam como medicação pré-anestésica no BIS dos pacientes com PC em uso crônico de anticonvulsivantes. MÉTODO: Foram avaliados três grupos de pacientes: PC sem uso de anticonvulsivantes, PC em uso de anticonvulsivante e outro grupo sem doença e sem uso de medicações (Grupo Controle. Na véspera da cirurgia, com os pacientes despertos e em decúbito dorsal, foi colocado o monitor do BIS e foram registrados os valores basais do BIS. No dia seguinte, 40 minutos antes da cirurgia, os pacientes receberam 0,6 mg.kg-1 de midazolam por via oral. Antes do início da anestesia, foi realizado o mesmo procedimento para registro do BIS, após o uso do midazolam. RESULTADOS: Foram estudados 107 pacientes - 39 pacientes do Grupo Controle e 68 com diagnóstico de PC. Desses, 17 faziam uso de anticonvulsivante. Com relação ao valor médio de BIS após o uso do midazolam, não houve diferença entres os pacientes do Grupo Controle e do Grupo PC que não tomavam anticonvulsivante, enquanto entre os pacientes que faziam uso de anticonvulsivantes houve diferença (p = 0,003. A possibilidade de diminuição do BIS após o uso do midazolam aumenta de acordo com o número de anticonvulsivantes usados pelo paciente. CONCLUSÕES: O uso crônico de anticonvulsivante associado ao midazolam via oral como medicação pré-anestésica pode levar à diminuição dos valores de BIS, configurando níveis profundos de hipnose.JUSTIFICATIVA Y OBJETIVOS: Los pacientes con parálisis cerebral (PC, a menudo usan fármacos para el tratamiento de enfermedades concomitantes, como las convulsiones. El midazolam es el hipnótico más utilizado como medicación preanestésica y no se conocen sus interacciones medicamentosas en los pacientes con PC. El objetivo de este estudio fue evaluar el midazolam como medicación preanestésica en el BIS de los pacientes con PC en uso crónico de antiepilépticos. MÉTODO: Se evaluaron tres grupos de pacientes: PC sin uso de antiepilépticos, PC en uso de antiepiléptico y otro grupo sin enfermedad y sin uso de medicaciones (grupo control. En la víspera de la cirugía, con los pacientes despiertos y en decúbito dorsal, fue colocado el monitor del BIS y se registraron los valores basales del BIS. Al día siguiente, 40 minutos antes de la cirugía, los pacientes recibieron 0,6 mg.kg-1 de midazolam por vía oral. Antes del inicio de la anestesia fue realizado el mismo procedimiento para registro del BIS, después del uso del midazolam. RESULTADOS: Fueron estudiados 107 pacientes, 39 pacientes del grupo control y 68 con diagnóstico de PC. De ellos, 17 usaban antiepilépticos. Con relación al valor promedio de BIS después del uso del midazolam, no hubo diferencia entres los pacientes del grupo control y del grupo PC que no tomaban antiepiléptico, mientras que los pacientes que usaban antiepilépticos fueron diferentes (p = 0,003. La posibilidad de disminución del BIS después del uso del midazolam, aumenta de acuerdo con el número de antiepiléptico usado por el paciente. CONCLUSIONES: El uso crónico de antiepiléptico asociado al midazolam vía oral como medicación preanestésica, puede conllevar a la disminución de los valores de BIS configurando niveles profundos de hipnosis.BACKGROUND AND OBJECTIVES: Patients with cerebral palsy (CP frequently receive drugs for the treatment of concomitant diseases, such as seizures. Midazolam is a benzodiazepine with hypnotic action most often used as pre-anesthetic medication and its drug interactions in patients with CP are unknown. The objective of the present study was to evaluate the effect of midazolam as pre-anesthetic drug on the BIS of patients with CP undergoing chronic treatment with anticonvulsa

  7. Disease: H00547 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available n Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pedi...AW Toward a molecular understanding of congenital heart disease. Circulation 91:4...The defect is often associated with Down syndrome (trisomy 21). Developmental dis...order; Cardiovascular disease CRELD1 [HSA:78987] Organic solvents Anticonvulsants Ibuprofen [CPD:C01588] Sul

  8. 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.

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

    DEFF Research Database (Denmark)

    Rode, Frederik; Svalø, Julie; Sheykhzade, Majid;

    2010-01-01

    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...

  10. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  11. 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.

  12. 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

  13. 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…

  14. 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...

  15. Epidemiology of Osteoporosis in Women with Cognitive Impairment

    Science.gov (United States)

    Schrager, Sarina

    2006-01-01

    Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…

  16. 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.

  17. 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

  18. Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V.

    Science.gov (United States)

    Roy, Saikat; Goud, N Rajesh; Matzger, Adam J

    2016-03-21

    This report highlights the discovery of a new polymorph of the anticonvulsant drug phenobarbital (PB) using polymer-induced heteronucleation (PIHn) and unravelling the crystal structure of the elusive form V. Both forms are characterized by structural, thermal and VT-Raman spectroscopy methods to elucidate phase transformation behavior and shed light on stability relationships.

  19. 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…

  20. 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....

  1. 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.

  2. 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 (pbark 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.

  3. 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...

  4. 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...

  5. Transient inhibitory seizures mimicking crescendo TIAs.

    Science.gov (United States)

    Lee, H; Lerner, A

    1990-01-01

    Somatic inhibitory seizures are thought to occur rarely. We describe a patient with somatic inhibitory seizures who initially presented with a clinical picture of crescendo transient ischemic attacks. He did not improve with anticoagulation, but the episodes ceased promptly after the administration of an anticonvulsant.

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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 ...

  11. 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 ...

  12. Atomic basis for therapeutic activation of neuronal potassium channels

    DEFF Research Database (Denmark)

    Kim, Robin Y; Yau, Michael C; Galpin, Jason D;

    2015-01-01

    Retigabine is a recently approved anticonvulsant that acts by potentiating neuronal M-current generated by KCNQ2-5 channels, interacting with a conserved Trp residue in the channel pore domain. Using unnatural amino-acid mutagenesis, we subtly altered the properties of this Trp to reveal specific...

  13. 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 ...

  14. 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…

  15. The role of sodium channels in the mechanism of action of antidepressants and mood stabilizers.

    Science.gov (United States)

    Bourin, Michel; Chenu, Franck; Hascoët, Martine

    2009-11-01

    Antidepressant drugs modify in different ways the activity of neurons, by increasing monoamines levels and by modulating ion channels. Sodium channels are molecular targets for antiepileptic drugs, which can also be mood stabilizers (i.e. lamotrigine, topiramate, phenytoin, carbamazepine, valproic acid). After a short overview on the sodium channels and the interaction with antidepressants and mood stabilizers, a comparison of the activity of both antidepressants and mood stabilizers with the addition of veratrine (sodium channel opener) on the forced swimming test (FST) in mice was presented. By comparing the antidepressant-like effect of the antidepressants (paroxetine, imipramine and desipramine) with the one of anticonvulsants (lamotrigine, phenytoin and topiramate) on the FST, it seems that the mechanism of action of anticonvulsants and antidepressants are different, because veratrine limits the activity of anticonvulsants but not of antidepressants. The anticonvulsants topiramate and phenytoin reduce the immobility time in the FST in a range of time similar to those induced by antidepressants, suggesting that the FST could be sensitive to both drugs. The magnitude of antidepressant-like effect of the lamotrigine (acting through an increase in monoaminergic neurotransmission and a blockade of sodium channels) in the FST is greater than what is obtained after administration of the other drugs, suggesting that this dual activity could be used as an augmentation strategy. Authors conclude that the development of new drugs acting on sodium channels could potentially be of interest as antidepressants, but also as augmentation strategies for classical antidepressants.

  16. 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.

  17. 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.

  18. Role of Intravenous Levetiracetam in Seizure Prophylaxis of Severe Traumatic Brain Injury Patients

    Directory of Open Access Journals (Sweden)

    BATOOL F. KIRMANI

    2013-11-01

    Full Text Available Traumatic brain injury (TBI can cause seizures and the development of epilepsy. The incidence of seizures varies from 21% in patients with severe brain injuries to 50% in patients with war-related penetrating TBI. In the acute and sub-acute periods following injury, seizures can lead to increased intracranial pressure and cerebral edema, further complicating TBI management. Anticonvulsants should be used for seizure prophylaxis and treatment. Phenytoin is the most widely prescribed anticonvulsant in these patients. Intravenous levetiracetam, made available in 2006, is now being considered as an alternative to phenytoin in acute care settings. When compared with phenytoin, levetiracetam has fewer side-effects and drug-drug interactions. In the following, the role of levetiracetam in TBI care and the supporting evidence is discussed.

  19. 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

  20. 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

  1. Levetiracetam compared to phenytoin for the prevention of postoperative seizures after craniotomy for intracranial tumours in patients without epilepsy.

    Science.gov (United States)

    Kern, K; Schebesch, K M; Schlaier, J; Hansen, E; Feigl, G C; Brawanski, A T; Lange, M

    2012-01-01

    Anticonvulsant drugs are frequently given after craniotomy. Phenytoin (PHT) is the most commonly used agent; levetiracetam (LEV) is a new anticonvulsant drug with fewer side effects. To compare the incidence of seizures in patients receiving either prophylactic PHT or LEV perioperatively, 971 patients undergoing a craniotomy were analysed retrospectively during a 2-year period. PHT was used routinely and LEV was administered when PHT was contraindicated. Seizures documented during the first 7 days after craniotomy were considered. A total of 235 patients were treated with an antiepileptic drug: 81 patients received LEV, and 154 patients, PHT. Two patients receiving LEV (2.5%) and seven receiving PHT (4.5%) had a seizure despite this treatment. No patient had a documented side effect or drug interaction. The data show that LEV may be an alternative option in patients with contraindications to PHT. PMID:22133815

  2. Steroids in childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Ramachandrannair Rajesh

    2006-01-01

    Full Text Available Treatment of epileptic encephalopathies can be very challenging as most anticonvulsant drugs fail to achieve good seizure control. Steroids are disease modifying as well as anticonvulsant in these conditions. Though steroids are accepted as the first-line treatment for infantile spasms, there are many unanswered questions with regard to the preparation, dose and duration of treatment. In this review a re-exploration of the literature is attempted. Putative mechanism of action of steroids in infantile spasms is also discussed. As steroids are being increasingly used in other epileptic encephalopathies and Rasmussen′s encephalitis, a brief discussion on the role of steroids in these conditions is attempted. The review ends with the discussion on newer neuroactive steroids in the management of epilepsy.

  3. 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.

  4. Synthesis of New Perhydropyrrolo[1,2-a]pyrazine Derivatives and Their Evaluation in Animal Models of Epilepsy

    Directory of Open Access Journals (Sweden)

    Maciej Dawidowski

    2014-10-01

    Full Text Available A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR and four-center three-component (U-4C-3CR variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated for the anticonvulsant activitiy in the maximal electroshock seizure (MES, subcutaneous Metrazole (scMET and minimal clonic seizure (6 Hz animal models of epilepsy. The efficacies of most derivatives in the 6 Hz model of pharmacoresistant partial seizures were markedly higher than in the ‘classical’ MES and scMET models. The most active compounds, (4R,8aR-3a, and (4S,8aS-6 displayed median effective doses (ED50 of 47.90 and 126.19 mg/kg, respectively, for the 6 Hz test.

  5. A concise synthesis of (±)-pregabalin via intramolecular C-H insertion of N-cumyl á-diazoacetamide

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhen-liang; LIU Wei-jun; CHEN Zhi-yong; Jiang Yao-zhong; HU Wen-hao

    2004-01-01

    Pregabalin 1 (3-aminomethyl-5-methyl hexanoic acid) is a potent anticonvulsant related to the inhibitory neurotransmitter a-aminobutyric acid (GABA).1 In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. Therefore,pregabalin can be used for the potential treatment of several central nervous system (CNS) disorders including epilepsy, neuropathic pain, anxiety and social phobia. Many synthetic routes have been developed to prepare pregabalin.2-3 However, there is a need to explore novel, practical and better synthetic approaches to pregabalin. Herein we report a concise synthesis of (±)-pregabalin from hydrolysis of corresponding (a)-lactam, which was obtained from the intramolecular C-H insertion of N-cumyl a-diazoacetamide 4.

  6. Burns and epilepsy--review and case report.

    Science.gov (United States)

    Gragnani, Alfredo; Müller, Bruno Rafael; Oliveira, Andrea Fernandes; Ferreira, Lydia Masako

    2015-03-01

    Decompensation of epilepsy in burned patients may be caused by several factors. Burn is a classic etiology of systemic inflammatory response syndrome, and evolves into two physiological phases. The first 48h after injury corresponds to the first phase involving severe hypovolemic shock. The second phase corresponds to the hypermetabolic response to burns. Altered pharmacokinetics of anticonvulsant drugs is observed. Albumin and other plasma proteins are reduced, leading to increased free fraction of phenytoin, resulting in greater clearance and a lower total drug concentration. Associated with metabolic changes of burned patient, this fact predisposes to seizures in epileptic burned patients. The authors present the case of an epileptic 36-year-old-woman who developed recurrent seizures after a thermal injury, despite using the same medications and doses of anticonvulsant drugs of last 12 years, with controlled epilepsy.

  7. 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.

  8. 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...

  9. Chemical and Pharmacological Researches on Hyoscyamus niger

    Institute of Scientific and Technical Information of China (English)

    LI Jun; SHI Ji; YU Xin-wen; SUN Jing-kuan; MEN Qi-ming; KANG Ting-guo

    2011-01-01

    The reports on chemical constituents of Hyoscyamus niger were summarized. The compounds include alkaloids, saponins, lignans, coumarinolignans, flavonoids, and some other nonalkaloidal compounds. TLC, HPLC, and GC were used for the qualitative and quantitative analyses of some chemical constituents in H. niger. Modern pharmacological experiments showed that H. niger had the analgesic, anti-inflammatory, antipyretic, anticonvulsant, spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory, urinary bladder relaxant, hypotensive, cardiosuppressant, vasodilator, antitumor, and feeding deterrent properties. In addition, the toxicities of this medicinal plant were also described.

  10. 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...

  11. 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 ...

  12. 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 ...

  13. Unilateral musical hallucinations and all that jazz.

    Science.gov (United States)

    Couper, J

    1994-09-01

    A 78-year-old hearing-impaired woman who presented to hospital with a stroke and a subsequent epileptic seizure later developed unilateral musical hallucinations in her better hearing (right) ear. She was found to have a left-sided temporal epileptic focus and the music ceased after a second anti-convulsant was introduced. Comments are made on unusual features of the hallucination and its probable causation.

  14. 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...

  15. 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...

  16. Acute myopia induced by topiramate: Report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Kalyan

    2005-01-01

    Full Text Available Topiramate, a new anticonvulsant, is also used for the prophylaxis of migraine and cluster headache. A serious but not often discussed side effect of the drug is the development of acute myopia and acute angle-closure glaucoma in the early stage of therapy that subsides rapidly with prompt discontinuation. One such case is reported here and the relevant literature in this regard is also reviewed.

  17. 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...

  18. [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

  19. Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala kainic acid model of status epilepticus in mice.

    Science.gov (United States)

    Diviney, Mairead; Reynolds, James P; Henshall, David C

    2015-10-01

    Benzodiazepines remain as the first-line treatment for status epilepticus (SE), but debate continues as to the choice and delivery route of pharmacotherapy. Lorazepam is currently the preferred anticonvulsant for clinical use, but midazolam has become a popular alternative, particularly as it can be given by nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in animal models. Here, we aimed to compare the efficacy of midazolam with that of lorazepam in an experimental model of focal-onset SE. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6 mice. Forty minutes later, mice were treated with an intraperitoneal injection of either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity, histology, and behavioral tests assessing recovery of function were evaluated and compared between groups. Intraperitoneal injection of either lorazepam or midazolam resulted in similar patterns of reduced EEG epileptiform activity during 1-hour recordings. Damage to the hippocampus and presentation of postinsult anxiety-related behavior did not significantly differ between treatment groups at 72h. However, return of normal behaviors such as grooming, levels of activity, and the evaluation of overall recovery of SE mice were all superior at 24h in animals given midazolam compared with lorazepam. Our results indicate that midazolam is as effective as lorazepam as an anticonvulsant in this model while also providing improved animal recovery after SE. These data suggest that midazolam might be considered by researchers as an anticonvulsant in animal models of SE, particularly as it appears to satisfy the requirements of refining procedures involving experimental animals at early time-points after SE.

  20. Temporal Lobe Epilepsy after Refractory Status Epilepticus: An Illustrative Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    J. Gordon Boyd

    2012-01-01

    Full Text Available New onset refractory status epilepticus (NORSE is a relatively newly defined disease entity, where otherwise healthy individuals develop unrelenting seizures that do not respond to conventional anticonvulsant therapy and may require months of therapy with anesthetic drugs. We have described a case of NORSE who subsequently developed mesial temporal lobe sclerosis (MTS and recurrent temporal lobe seizures. We discuss the possible pathophysiological mechanisms by which refractory seizures may contribute to the development of temporal lobe epilepsy (TLE.

  1. 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 ...

  2. 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 ...

  3. 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...

  4. El pretratamiento agudo y subcrónico con fármacos anticonvulsivantes modifica las crisis generalizadas inducidas por el pentilenetetrazol en el ratón

    OpenAIRE

    Luisa L. Rocha

    2008-01-01

    Objetives: The increased GABA content or administration of a centrally active GABA-mimetic agent have been used as a efficacious anticonvulsant therapeutic approach. However, it has been suggested that the use of drugs that continually and noncontingently alter synaptic transmission could alter at the nervous system. The present study was carried out to investigate the effects of acute (one administration) and subchronic (7 daily administrations) treatments with Diazepam (DZP; 10 mg/kg, ip), ...

  5. 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...

  6. 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...

  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. 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.

  11. 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...

  12. [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

  13. 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 ...

  14. 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...

  15. 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, ...

  16. 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...

  17. 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

  18. 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...

  19. 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...

  20. 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...

  1. 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

  2. Aqueous Stem Bark Extract of Stereospermum Kunthianum (Cham, Sandrine Petit) Protects Against Generalized Seizures in Pentylenetetrazole and Electro-Convulsive Models in Rodents

    OpenAIRE

    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 anticonvuls...

  3. 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,...

  4. 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...

  5. 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. ...

  6. 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...

  7. 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...

  8. 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...

  9. Laser-Assisted Periodontal Management of Drug-Induced Gingival Overgrowth under General Anesthesia: A Viable Option

    OpenAIRE

    Tupili Muralikrishna; Butchibabu Kalakonda; Sumanth Gunupati; Pradeep Koppolu

    2013-01-01

    Gingival overgrowth/hyperplasia can be attributed to several causes, but drug-induced gingival overgrowth/hyperplasia arises secondarily to prolonged use of antihypertensive drugs, anticonvulsants and immunosuppressants. The management is complex in nature considering the multitude of factors involved such as substitution of drug strict plaque control along with excision of the tissue to be performed under local anesthesia as outpatient. In the recent times, the patient’s psychological fear o...

  10. Amlodipine-induced Gingival Hyperplasia - A Case Report and Review.

    Science.gov (United States)

    Madi, M; Shetty, S R; Babu, S G; Achalli, S

    2015-06-01

    Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants are the three main classes of drugs known to cause drug-induced gingival hypertrophy or hyperplasia. Among the calcium channel blockers, nifedipine administration has most frequently been associated with medication-related gingival hyperplasia. The incidence with amlodipine, which has a mode of action pharmacodynamically comparable to nifedipine, has rarely been reported. Here, we present a rare case of amlodipine-induced gingival hyperplasia in a hypertensive patient.

  11. 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

  12. 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 ...

  13. 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

  14. 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...

  15. [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

  16. 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...

  17. 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.

  18. 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.

  19. Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.

    Science.gov (United States)

    Shannon, Harlan E; Yang, Lijuan

    2004-01-01

    Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null mutant mice are more susceptible to kainate-induced seizures. In order to better understand the potential role of NPY in epileptogenesis, the present studies investigated the development of amygdala kindling, post-kindling seizure thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in 129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine- and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice either when kindling stimuli were presented once daily for at least 20 days, or, 12 times daily for 2 days. However, during kindling development, the NPY(-/-) mice had higher seizure severity scores and longer afterdischarge durations than the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower afterdischarge thresholds and longer afterdischarge durations than NPY (+/+) mice. Carbamazepine and levetiracetam increased the seizure thresholds of both NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for both kainate- and pilocarpine-induced seizures. The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis. In addition, a lack of NPY does not appear to confer drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in both wild type (WT) and NPY null mutant mice.

  20. 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.

  1. [Effect of citicoline on the development of chronic epileptization of the brain (pentylenetetrazole kindling) and acute seizures reaction of kindled mice C57Bl/6].

    Science.gov (United States)

    Kuznetzova, L V; Karpova, M N; Zinkovsky, K A; Klishina, N V

    2014-01-01

    In experiments on mice C57Bl/6 was studied effects of citicoline (500 mg/kg, i.p.) on development of chronically epileptization of the brain--pentylenetetrazole (PTZ) kindling (30 mg/kg PTZ, i.p. during 24 days) and on acute generalized seizures (i.v., 1% solution of PTZ with the speed of 0.01 ml/s). It was shown that daily injection of citicoline an hour before the introduction of PTZ had no effect on development of chronically epileptization of the brain --PTZ-kindling (the latency of seizures appearance and their severity). However, citicoIine posses anticonvulsive effects on acute seizures in kindled mice. In animals with increased seizure susceptibility of the brain caused by kindling and severity of seizures 2-3 points injection citicoline after 14 days of kindling had anticonvulsive effect, increasing the threshold clonic seizures. Injection of citicoline during 24 days of kindled animals and severity of seizures 3-5 points caused the increase of thresholds as clonic and tonic phase of seizures with lethal outcome. Thus, the anticonvulsant effect of citicoline more pronounced in the long-term use.

  2. Effect of low-frequency stimulation on kindling induced changes in rat dentate gyrus: an ultrastructural study.

    Science.gov (United States)

    Rohani, Razieh; Piryaei, Abbas; Jahanshahi, Ali; Sadeghi, Yousef; Mirnajafi-Zadeh, Javad

    2014-03-01

    It has been shown that low-frequency stimulation (LFS) can induce anticonvulsant effects. In this study, the effect of different LFS frequencies on kindling induced behavioral and ultrastructural changes was investigated. For induction of kindled seizures in rats, stimulating and recording electrodes were implanted in perforant path and dentate gyrus, respectively. Animals were stimulated in a rapid kindling manner. Different groups of animals received LFS at different frequencies (0.5, 1 and 5 Hz) following kindling stimulations and their effects on kindling rate were determined using behavioral and ultrastructural studies. Kindling stimulations were applied for 7 days. Then, the animals were sacrificed and their dentate gyrus was sampled for ultrastructural studies under electron microscopy. All three used LFS frequencies (0.5, 1 and 5 Hz) had a significant inhibitory effect on kindling rate and decreased afterdischarge duration and the number of stimulations to achieve stage 4 and 5 seizures significantly. In addition, application of LFS prevented the increase in the post-synaptic density and induction of concave synaptic vesicles following kindling. There was no significant change between anticonvulsant effects of LFS at different frequencies. Obtained results show that LFS application can prevent the neuronal hyperexcitability by preventing the ultrastructural changes during kindling and this may be one of the mechanisms of LFS anticonvulsant effects.

  3. 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.

  4. 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

  5. New-onset refractory status epilepticus in an adult with an atypical presentation of cat-scratch disease: successful treatment with high-dose corticosteroids.

    Science.gov (United States)

    Laswell, Emily M; Chambers, Kasandra D; Whitsel, Danielle R; Poudel, Kiran

    2015-06-01

    New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam. The patient was placed on continuous electroencephalography (EEG) monitoring and was treated further with multiple antiepileptics, which were titrated aggressively based on EEG readings and therapeutic drug levels; despite this treatment, EEG monitoring revealed continued seizures. Thus, high-dose corticosteroids were started for seizure control. Her workup included computed tomography and magnetic resonance imaging of the head, a lumbar puncture, toxicology screening, and extensive testing for multiple infectious and inflammatory etiologies. The patient's history revealed recent exposure to a new cat. Serologic results were positive for Bartonella henselae, and she was diagnosed with cat-scratch disease (CSD). She did not have the typical presentation of symptoms of lymphadenopathy, however, which is common in CSD. Doxycycline 100 mg and rifampin 300 mg twice daily were added to the patient's anticonvulsant and corticosteroid therapy. She was hospitalized for a total of 26 days and discharged with only minor neurologic impairment (short-term memory deficits and minor cognitive problems). The patient was discharged receiving antiepileptics, antibiotics, and a corticosteroid taper. To our knowledge, this is the first clinically known case of NORSE secondary to CSD without typical CSD symptoms in the adult population. The patient failed to respond to traditional anticonvulsant therapy alone. With the addition of high

  6. A pharmacological basis of herbal medicines for epilepsy.

    Science.gov (United States)

    Sucher, Nikolaus J; Carles, Maria C

    2015-11-01

    Epilepsy is the most common chronic neurological disease, affecting about 1% of the world's population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs). Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures. Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals. Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs. Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays. To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids. Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs. Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites. Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy. Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development. In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Neurocysticercosis in Wisconsin: 3 cases and a review of the literature.

    Science.gov (United States)

    Naddaf, Elie; Seeger, Susanne K; Stafstrom, Carl E

    2014-04-01

    Neurocysticercosis is the most common parasitic infection of the brain. Endemic in many regions of the world, neurocysticercosis is now showing up in nonendemic areas such as Wisconsin. We present 3 patients that illustrate features typical for neurocysticercosis in anon-endemic area, including immigrant/travel status, presentation with focal seizures, classic magnetic resonance imaging features of single enhancing lesions, and good response to treatment with anticonvulsants, anti-inflammatory agents, and cysticidal drugs. It behooves physicians involved in the care of at-risk populations to be aware of the clinical features, radiographic signs, diagnostic tests, and general principles for treating neurocysticercosis.

  13. 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...... chloride (0.9 mg/kg) and lamotrigine (20 mg/kg), which are known to effectively stabilize mood in humans, both significantly decreased AMPH+CDP-induced locomotor activity without affecting basal locomotor activity. The results furthermore indicate that retigabine, like lithium and lamotrigine...

  14. 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...

  15. 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

  16. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

    DEFF Research Database (Denmark)

    Falah, M; Madsen, C; Holbech, J V;

    2012-01-01

    as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study...... of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non...

  17. 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.

  18. 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.

  19. Pharmacotherapy of cancer pain in dogs and cats suffering from cancer

    Directory of Open Access Journals (Sweden)

    Milovanović Mirjana

    2010-01-01

    Full Text Available Pain is an important symptom that accompanies cancer disease. Cancer pain is a chronic pain of medium to strong intensity, and it usually seriously impairs the quality of life of the cancer patients. In dogs and cats, the management of cancer pain includes drugs from different pharmacological groups. They are non-opioid and opioid analgesics, NMDA antagonists, anticonvulsant drugs, tricyclic antidepressants and steroids. Some of them are registered for use in veterinary medicine, and some are drugs for use in human medicine. .

  20. 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

  1. 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

  2. Drug: D00714 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 08 264.3196 D00714.gif Anesthetic [intravenous]; Anticonvulsant Therapeutic category: 1115 ATC code: N01AF03 N05CA19 Barbiturates...y organs 11 Agents affecting central nervous system 111 General anesthetics 1115 Barbiturates and thiobarbiturates...TC) classification [BR:br08303] N NERVOUS SYSTEM N01 ANESTHETICS N01A ANESTHETICS, GENERAL N01AF Barbiturates..., plain N01AF03 Thiopental D00714 Thiopental sodium (JP16/USP/INN) N05 PSYCHOLEPTICS N05C HYPNOTICS AND SEDATIVES N05CA Barbiturates

  3. Drug: D05775 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05775 Drug Rufinamide (JAN/USAN/INN); Banzel (TN) C10H8F2N4O 238.0666 238.1935 D05...03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AF Carboxamide derivatives N03AF03 Rufinamide D05775 Rufinamide (JAN/USAN/INN) USP dru... Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting nervous system and sensory organs 11... Agents affecting central nervous system 113 Antiepileptics 1139 Others D05775 Ru...g classification [BR:br08302] Anticonvulsants Sodium Channel Agents Ru

  4. A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy.

    Science.gov (United States)

    Löscher, W; Lehmann, H; Behl, B; Seemann, D; Teschendorf, H J; Hofmann, H P; Lubisch, W; Höger, T; Lemaire, H G; Gross, G

    1999-01-01

    Antagonists at the ionotropic non-NMDA [AMPA (amino-methyl proprionic acid)/kainate] type of glutamate receptors have been suggested to possess several advantages compared to NMDA (N-methyl-D-aspartate) receptor antagonists, particularly in terms of risk/benefit ratio, but the non-NMDA receptor antagonists available so far have not fulfilled this promise. From a large series of pyrrolyl-quinoxalinedione derivatives, we selected six new competitive non-NMDA receptor antagonists. The basis of selection was high potency and selectivity for AMPA and/or kainate receptors, high in vivo potency after systemic administration, and an acceptable ratio between neuroprotective or anticonvulsant effects and adverse effects. Pharmacological characteristics of these novel compounds are described in this study with special emphasis on their effects in the kindling model of temporal lobe epilepsy, the most common type of epilepsy in humans. In most experiments, NBQX and the major antiepileptic drug valproate were used for comparison with the novel compounds. The novel non-NMDA receptor antagonists markedly differed in their AMPA and kainate receptor affinities from NBQX. Thus, while NBQX essentially did not bind to kainate receptors at relevant concentrations, several of the novel compounds exhibited affinity to rat brain kainate receptors or recombinant kainate receptor subtypes in addition to AMPA receptors. One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors. All compounds potently blocked AMPA-induced cell death in vitro and, except LU 97175, AMPA-induced convulsions in vivo. In the kindling model, compounds with a high affinity for GluR7 (LU 97175) or compounds (LU 115455, LU 136541) which potently bind to AMPA receptors and low affinity kainate receptor subunits were potent anticonvulsants in the kindling model, whereas the AMPA

  5. 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...

  6. Drug: D08964 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08964 Drug Perampanel (USAN); Fycompa (TN) C23H15N3O 349.1215 349.3847 D08964.gif ...ATC) classification [BR:br08303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AX Other antiepileptics N03AX22 Perampane...l D08964 Perampanel (USAN) USP drug classification [BR:br08302] Anticonvulsants Glu...tamate Reducing Agents Perampanel D08964 Perampanel (USAN) Target-based classific...PA receptor [HSA:2890 2891 2892 2893] [KO:K05197 K05198 K05199 K05200] Perampanel [ATC:N03AX22] D08964 Perampanel

  7. Effects of antiepileptic drugs in electrophysiological tests.

    Science.gov (United States)

    Rump, S; Kowalczyk, M

    1987-01-01

    Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity.

  8. 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.

  9. Drug: D00512 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00512 Drug Phenytoin (JP16/USP/INN); Dilantin (TN) C15H12N2O2 252.0899 252.268 D00...here is a strong association between the risk of developing SJS/TEN with Phenytoin treatment and the presenc...ystem 113 Antiepileptics 1132 Hydantoins D00512 Phenytoin (JP16/USP/INN) Anatomic...PTICS N03AB Hydantoin derivatives N03AB02 Phenytoin D00512 Phenytoin (JP16/USP/INN) USP drug classification ...[BR:br08302] Anticonvulsants Sodium Channel Agents Phenytoin D00512 Phenytoin (JP

  10. 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.

  11. 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

  12. 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

  13. 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....

  14. 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.

  15. 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 ...

  16. 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/...

  17. 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.

  18. 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.

  19. [Is there a specific pharmacological treatment for anxiety disorders? Summary of a controversy].

    Science.gov (United States)

    Todorov, Christo

    2004-01-01

    The acute pharmacological treatment of anxiety disorders is barely specific with the exception of the obsessive-compulsive disorder: it responds preferentially to potent serotoninergic antidepressants only. For all other anxiety disorders all antidepressants regardless of their mechanism of action could be equally efficient thanks to their common class effect and are considered to be the pharmacological treatment of first choice. Benzodiazepines that also share a common class effect are recommended as possible and temporary adjuvants. Augmentation strategies for the cases of refractory anxiety disorders are also non-specific: lithium, antipsychotics, anticonvulsants.

  20. 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

  1. Laser-Assisted Periodontal Management of Drug-Induced Gingival Overgrowth under General Anesthesia: A Viable Option.

    Science.gov (United States)

    Muralikrishna, Tupili; Kalakonda, Butchibabu; Gunupati, Sumanth; Koppolu, Pradeep

    2013-01-01

    Gingival overgrowth/hyperplasia can be attributed to several causes, but drug-induced gingival overgrowth/hyperplasia arises secondarily to prolonged use of antihypertensive drugs, anticonvulsants and immunosuppressants. The management is complex in nature considering the multitude of factors involved such as substitution of drug strict plaque control along with excision of the tissue to be performed under local anesthesia as outpatient. In the recent times, the patient's psychological fear of the treatment with the use of surgical blade and multiple visits has developed the concept of single visit treatment under general anesthesia incorporating a laser as viable option. The present case highlights the new method of management of gingival overgrowth.

  2. Prosthodontic treatment for a patient with advanced hydantoin-associated gingival hyperplasia: a case report.

    Science.gov (United States)

    Hayakawa, I; Osada, E; Morisawa, M; Nakagawa, Y; Watanabe, I

    1996-04-01

    A patient in whom gingival hyperplasia was caused by prolonged use of an anticonvulsant drug (hydantoin) is described. Advanced gingival hyperplasia and significant displacement of the remaining teeth caused severe damage, especially to the patient's appearance. It was not possible to cure the problems completely with routine periodontal treatment. It was decided to extract all the remaining teeth and restore function and esthetics early with complete dentures. Cephalometric analysis was used to determine the degree to which the teeth had drifted. During fabrication of the dentures, the analysis was very useful in deciding the position of the anterior teeth and checking the vertical dimension of occlusion.

  3. Recent developments of 2-aminothiazoles in medicinal chemistry.

    Science.gov (United States)

    Das, Debasis; Sikdar, Papiya; Bairagi, Moumita

    2016-02-15

    The 2-aminothiazole (2-AT) core is an active pharmacophore and used in medicinal chemistry and drug discovery research. A number of drugs with 2-AT core are in the market, e.g. Famotidine, Cefdinir, Meloxcam etc. Recently, 2-AT core has been explored for many more important therapeutic areas and identified new 2-aminothiazoles with anticancer, antitumor, antidiebatic and anticonvulsant activity. In this review, we discuss the newly identified and developed 2-aminothiazoles in recent years and their use in medicinal chemistry and pharmacology.

  4. Lithium and renal and upper urinary tract tumors

    DEFF Research Database (Denmark)

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

    2015-01-01

    individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii......) 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...

  5. Ictal and interictal 99mTc-HMPAO brain SPECT of a MELAS case presented with epilepsy-like visual hallucination.

    Science.gov (United States)

    Wei, Cheng-Yu; Hsiao, Heng-Long; Chen, Shang-Chi; Hung, Guang-Uei; Kao, Chia-Hung

    2012-09-01

    A 55-year-old woman was diagnosed with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). She was referred for Tc-HMPAO brain SPECT because of visual hallucinations, which were suspected to be related to epileptic seizures. Ictal SPECT images showed remarkable hyperperfusion in the left occipital cortex, which returned to near-normal status on the interictal SPECT images after treatment with anticonvulsants. It is very rare to see such an ictal SPECT image of epileptic or epilepsy-like disorders, especially in the setting of MELAS syndrome with visual hallucination.

  6. 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

  7. 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

  8. 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

  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. 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.

  11. 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

  12. 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

  13. Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine

    Directory of Open Access Journals (Sweden)

    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.

  14. Clinical presentation and etiology of osteomalacia/rickets in adolescents

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    Mohammad A Hazzazi

    2013-01-01

    Full Text Available This study was conducted to determine the causes and clinical presentations of osteomalacia/rickets in adolescents seen at the King Abdulaziz Medical City (KAMC, Riyadh. Because osteomalacia and rickets constitute the same entity, the term osteomalacia will be used for future discussion. A retrospective file review was performed on all adolescents (10-16 years with osteomalacia, defined as alkaline phosphatase levels ≥500 IU/L, seen at the KAMC, Riyadh, from 2000 to 2006. We recorded the signs and symptoms, dietary history and amount of sun exposure at presentation. A total of 135 patients were found to fit the inclusion criteria for the study. Of them, 57 had nutritional causes, with a mean age of 13.2 years, and included 32 females. At diagnosis, 22 patients were found to have bone pain, 10 had bone deformities, eight had pathological fractures and 17 were asymptomatic. Secondary causes for osteomalacia were found in 59 cases who had liver and renal disease and in 19 other patients who were on medications such as anticonvulsants and steroids, which are known to cause osteomalacia. Our study indicates that osteomalacia is a significant health burden that deserves special attention. Bone pain is the most common presenting symptom at diagnosis. Because of the high risk of osteomalacia associated with the use of anticonvulsants and steroids, it is advised that all patients on these drugs should be routinely screened for secondary osteomalacia.

  15. 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.

  16. A pharmacological study in the kindling model of epilepsy.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-10-01

    The anticonvulsant properties of carbamazepine were evaluated in the kindled amygdaloid seizure model in rats. Carbamazepine significantly raised the threshold for seizures, reduced the duration of elicited afterdischarges and attenuated the severity of seizures in previously-kindled rats, at doses that did not cause sedation or ataxia. A similar reduction in the duration of elicited afterdischarges and severity of seizures was seen after suprathreshold stimulation (400 mu A) with doses of carbamazepine that were without obvious sedative or ataxic effects. After acute intraperitoneal injections (solvent = 2% Tween-80 and 70% propylene glycol), the maximum anticonvulsant effectiveness against suprathreshold stimulation was seen at 30 min. When administered daily (13 days) during acquisition or development of kindling, carbamazepine (25 and 50 mg/kg, i.p.) had variable effects on kindling. Neither dose consistently reduced the duration of elicited afterdischarges during the acquisition phase. Both groups tended to reduce the developing seizure, with the smaller dose of carbamazepine (25 mg/kg) resulting in a more consistent and significant reduction in severity of seizures. No significant differences in number of daily stimulations needed to reach fully kindled seizures were found. Previous studies have reported variable results with carbamazepine and the kindled amygdaloid seizure in rats. The present study provides a comprehensive evaluation of carbamazepine in this model of epilepsy and discusses the results with regard to the finding reported previously.

  17. New aspects in the pharmacology of kindling implications for mechanism of of action in kindling.

    Science.gov (United States)

    Schmidt, J

    1987-01-01

    Kindling is a long-lasting, transsynaptic, pathway-specific plastic change in brain function. It has been proposed as a model of neural plasticity, learning and memory, as well as a model of epilepsy. To elucidate the action of substances characterized by their ability to improve learning and memory and to have an activatory, protective and function restoring effect on nerve cells in distress, the effects of nootropic drugs and of antioxidative acting substances on the development of kindling and the seizure behavior in the kindled state were investigated. Nootropic drugs suppress the development of pentetrazol (PTZ)- and amygdala-kindling and possess anticonvulsive potency preferentially in kindled rats. In comparison to amygdala-kindling the substances were found to be more effective against PTZ-kindled seizures. Chemically different antioxidants in doses known to scavenge free radicals suppress markedly the development of kindling and possess anticonvulsant potency in chemically and electrically kindled rats. The results provide arguments in favor of functional alterations of transmission relevant membrane processes with structural and functional reorganization of membrane constituents and lead to the assumption that the changes mainly in part rest on a selective and focal involvement of free radicals. It is proposed that enhanced calcium entry into neurons and consequent biochemical alterations connected with a focal increase in free radicals is part of the mechanisms underlying kindling phenomenon.

  18. [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.

  19. 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

  20. 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.

  1. [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

  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. Preliminary pharmacological screening of Bixa orellana L. leaves.

    Science.gov (United States)

    Shilpi, Jamil Ahmad; Taufiq-Ur-Rahman, Md; Uddin, Shaikh Jamal; Alam, Md Shahanur; Sadhu, Samir Kumar; Seidel, Véronique

    2006-11-24

    Preliminary pharmacological studies were performed on the methanol extract of Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological, anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal motility. All studies were conducted in mice using doses of 125, 250 and 500 mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose-dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A statistically significant decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. In the strychnine-induced anticonvulsant test, the extract increased the average survival time of the test animals (statistically significant at 250 and 500 mg/kg). The extract significantly and dose-dependently reduced the writhing reflex in the acetic acid-induced writhing test. Antidiarrhoeal activity was supported by a statistically significant decrease in the total number of stools (including wet stools) in castor oil-induced diarrhoea model. A statistically significant delay in the passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal motility test. The extract was further evaluated in vitro for antioxidant and antibacterial activity. It revealed radical scavenging properties in the DPPH assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected causative agents of diarrhoea and dysentery, including Shigella dysenteriae. PMID:16963211

  4. 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

  5. Enantioselective synthesis and teratogenicity of propylisopropyl acetamide, a CNS-active chiral amide analogue of valproic acid.

    Science.gov (United States)

    Spiegelstein, O; Bialer, M; Radatz, M; Nau, H; Yagen, B

    1999-01-01

    Propylisopropyl acetamide (PID), an amide analogue of the major antiepileptic drug valproic acid (VPA), possesses favorable anticonvulsant and CNS properties. PID contains one chiral carbon atom and therefore exists in two enantiomeric forms. The purpose of this work was to synthesize the two PID enantiomers and evaluate their enantiospecific teratogenicity. Enantioselective synthesis of PID enantiomers was achieved by coupling valeroyl chloride with optically pure (4S)- and (4R)-benzyl-2-oxazolidinone chiral auxiliaries. The two oxazolidinone enolates were alkylated with isopropyl triflate, hydrolyzed, and amidated to yield (2R)- and (2S)-PID. These two PID enantiomers were obtained with excellent enantiomeric purity, exceeding 99.4%. Unlike VPA, both (2R)- and (2S)-PID failed to exert teratogenic effects in NMRI mice following a single 3 mmol/kg subcutaneous injection. From this study we can conclude that individual PID enantiomers do not demonstrate stereoselective teratogenicity in NMRI mice. Due to its better anticonvulsant activity than VPA and lack of teratogenicity, PID (in a stereospecific or racemic form) has the potential to become a new antiepileptic and CNS drug.

  6. 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

  7. Proconvulsant effects of estriol, the third estrogen, in the mouse PTZ-kindling model.

    Science.gov (United States)

    Ahmad, Aakifa; Vohora, Divya

    2014-10-01

    The effect of estriol, the third estrogen, was evaluated for its effect on pentylenetetrazole (PTZ)-kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. The seizure severity during induction of kindling and percentage incidence of animals kindled at the end of 5 weeks was recorded. Motor function was assessed using a grip strength meter while spatial memory was assessed in a cross maze. Estriol (0.005 and 0.01 mg/kg i.p.) reduced the time for induction of kindling from 5 weeks to 3 and 2 weeks for male and female mice respectively and enhanced the percentage incidence of seizures. Clomiphene (0.9 mg/kg i.p.) delayed the development of kindling and produced anticonvulsant effects. It also partially reversed the proconvulsant effects of estriol. On grip strength test and spontaneous alternation behaviour, a significant decline was observed in kindled mice which was further reduced by pre-treatment with estriol. Both clomiphene and diazepam were unable to reverse the reduced GS of PTZ-kindled mice but enhanced the percentage alternation of such animals. The study shows that estriol has powerful proconvulsant effects. Its administration in hormone replacement therapy or other indications, thus, requires careful monitoring in patients susceptible to epileptic seizures. The anticonvulsant effects of clomiphene requires further investigations.

  8. 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

  9. 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...

  10. Cannabidiol and epilepsy: Rationale and therapeutic potential.

    Science.gov (United States)

    Leo, Antonio; Russo, Emilio; Elia, Maurizio

    2016-05-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue. To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy. In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action. However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD. In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis. Likewise, clinical evidence seems to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile. However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising. PMID:26976797

  11. Adverse Cutaneous Reactions to Psychotropic Drugs: A Review

    Directory of Open Access Journals (Sweden)

    Filipa Novais

    2015-11-01

    Full Text Available Introduction: Psychotropic drugs are often implicated in cutaneous adverse drug reactions. While most of these reactions have a benign character, it is still important, however, to consider its role in the increasing stigma and treatment adherence. A small number of the cutaneous adverse drug reactions can develop into serious and potentially fatal conditions. Objectives: This article aims to review the most common cutaneous adverse drug reactions in patients taking psychotropic drugs. Methods: In this study, a search was carried out in the MEDLINE database for English language articles published , from 1999 to 2014, using as keywords: psychiatric, psychotropic, cutaneous, adverse reaction, antidepressive agents, antipsychotics, benzodiazepines, mood stabilizers, anticonvulsant, dementia. Information available from the Portuguese regulatory and supervising agency (Infarmed was also included.Results: 121 articles were found with reference to cutaneous adverse drug reactions associated with psychotropic drugs. The drugs most frequently reported as associated with such adverse effects were anticonvulsants used as mood stabilizers, followed by the antipsychotics . The antidementia drugs were rarely associated with serious cutaneous adverse reactions. Discussion and Conclusion: Cutaneous drug adverse reactions are common in psychiatric clinical practice and typically are minor in severity. The most severe reactions are most often associated with the use of mood stabilizing medications. Some of these side effects can be solved with reduction or drug discontinuation. More severe cases should be referred to a specialist in dermatology.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Preclinical evaluation of 2,2,3,3-tetramethylcyclopropanecarbonyl-urea, a novel, second generation to valproic acid, antiepileptic drug.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Steve White, H; Wilcox, Karen S; Lamb, John G; Pappo, Orit; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2006-09-01

    2,2,3,3-Tetramethylcyclopropanecarbonylurea (TMCU) is an amide derivative of a tetramethylcyclopropyl analogue of valproic acid (VPA), one of the leading antiepileptic drugs. Structural considerations used in the design of TMCU aimed to enhance the anticonvulsant potency of VPA and to prevent its two life-threatening side effects; i.e., teratogenicity and hepatotoxicity. The anticonvulsant activity of TMCU was evaluated in the MES, scMet, 6-Hz, scBic and scPic tests, and also in the hippocampal kindling model of partial seizures and lamotrigine-resistant amygdala kindling model of therapy-resistant seizures. Minimal motor impairment was determined using the rotorod test in mice and the positional sense test, muscle tone test, and gait and stance test in rats. The antinociceptive effect of TMCU was evaluated in the mouse formalin model of acute-tonic pain. The molecular mechanisms of action of TMCU were investigated in electrophysiological studies using the whole-cell patch-clamp technique. Teratogenicity studies were performed in a SWV/Fnn-mouse model of VPA-induced teratogenicity. TMCU hepatotoxicity was evaluated following 1-week intraperitoneal and oral administration of 50, 250 and 500 mg/kg doses to rats. In the hepatotoxicity study the blood levels of TMCU were evaluated at day 1 and day 7 of the treatment. TMCU mutagenicity was evaluated in the Ames test.

  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. Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

    Science.gov (United States)

    Cho, Suengmok; Han, Daeseok; Kim, Seon-Bong; Yoon, Minseok; Yang, Hyejin; Jin, Young-Ho; Jo, Jinho; Yong, Hyeim; Lee, Sang-Hoon; Jeon, You-Jin; Shimizu, Makoto

    2012-01-01

    Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA(A)-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA(A)-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA(A)-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

  20. [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

  1. Post-traumatic epilepsy: current and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Szaflarski JP

    2014-08-01

    Full Text Available Jerzy P Szaflarski,1,3 Yara Nazzal,1,3 Laura E Dreer2 1Department of Neurology, 2Department of Ophthalmology, 3UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Traumatic brain injury (TBI leads to many undesired problems and complications, including immediate and long-term seizures/epilepsy, changes in mood, behavioral, and personality problems, cognitive and motor deficits, movement disorders, and sleep problems. Clinicians involved in the treatment of patients with acute TBI need to be aware of a number of issues, including the incidence and prevalence of early seizures and post-traumatic epilepsy (PTE, comorbidities associated with seizures and anticonvulsant therapies, and factors that can contribute to their emergence. While strong scientific evidence for early seizure prevention in TBI is available for phenytoin (PHT, other antiepileptic medications, eg, levetiracetam (LEV, are also being utilized in clinical settings. The use of PHT has its drawbacks, including cognitive side effects and effects on function recovery. Rates of recovery after TBI are expected to plateau after a certain period of time. Nevertheless, some patients continue to improve while others deteriorate without any clear contributing factors. Thus, one must ask, ‘Are there any actions that can be taken to decrease the chance of post-traumatic seizures and epilepsy while minimizing potential short- and long-term effects of anticonvulsants?’ While the answer is ‘probably,’ more evidence is needed to replace PHT with LEV on a permanent basis. Some have proposed studies to address this issue, while others look toward different options, including other anticonvulsants (eg, perampanel or other AMPA antagonists, or less established treatments (eg, ketamine. In this review, we focus on a comparison of the use of PHT versus LEV in the acute TBI setting and summarize the clinical aspects of seizure prevention in humans with

  2. Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy.

    Science.gov (United States)

    Löscher, W

    1998-04-01

    It is widely accepted that excitatory amino acid transmitters such as glutamate are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using NMDA receptors, but more recent evidence indicates potential roles for ionotropic non-NMDA (AMPA/kainate) and metabotropic glutamate receptors as well. Based on the role of glutamate in the development and expression of seizures, antagonism of glutamate receptors has long been thought to provide a rational strategy in the search for new, effective anticonvulsant drugs. Furthermore, because glutamate receptor antagonists, particularly those acting on NMDA receptors, protect effectively in the induction of kindling, it was suggested that they may have utility in epilepsy prophylaxis, for example, after head trauma. However, first clinical trials with competitive and uncompetitive NMDA receptor antagonists in patients with partial (focal) seizures, showed that these drugs lack convincing anticonvulsant activity but induce severe neurotoxic adverse effects in doses which were well tolerated in healthy volunteers. Interestingly, the only animal model which predicted the unfavorable clinical activity of competitive NMDA antagonists in patients with chronic epilepsy was the kindling model of temporal lobe epilepsy, indicating that this model should be used in the search for more effective and less toxic glutamate receptor antagonists. In this review, results from a large series of experiments on different categories of glutamate receptor antagonists in fully kindled rats are summarized and discussed. NMDA antagonists, irrespective whether they are competitive, high- or low-affinity uncompetitive, glycine site or polyamine site antagonists, do not counteract focal seizure activity and only weakly, if at all, attenuate propagation to secondarily generalized seizures in this model, indicating that once kindling is established, NMDA receptors are not critical for the expression of

  3. Stiripentol for the treatment of Dravet syndrome

    Directory of Open Access Journals (Sweden)

    Chiron C

    2014-04-01

    Full Text Available Catherine Chiron1–31INSERM U1129, Paris, France; 2Paris Descartes University, Paris, France; 3CEA, Gif-sur-Yvette, FranceAbstract: Stiripentol (marketed by Biocodex as Diacomit® is an anticonvulsant drug, structurally unrelated to any other compound, which has recently been approved as adjunctive therapy with clobazam and valproate for Dravet syndrome in Europe, Canada, and Japan. This rare form of early childhood epilepsy is associated with subsequent cognitive impairment, significant risk of death, and high pharmacoresistance. Based on an efficacy signal of stiripentol added to clobazam and valproate in an observational, prospectively conducted, exploratory study including 10% of children with Dravet syndrome, a randomized placebo-controlled trial was specifically dedicated to patients with Dravet syndrome inadequately controlled by clobazam and valproate. Results showed significantly higher responder rates (71% versus 5%; P<0.0001 and decrease in seizure frequency (-69% versus +7%; P<0.002 on stiripentol than on placebo. A second, independently performed, randomized controlled trial confirmed these results 2 years later, and both trials were plotted in a meta-analysis. Efficacy was supported by three subsequent observational studies, with, respectively, 46 (France, 23 (Japan, and 82 (USA children with Dravet syndrome treated with stiripentol for up to 5 years. Based on the experiences of more than 2,000 patients with Dravet syndrome who were exposed to stiripentol, drowsiness, loss of appetite, and weight loss are the most frequent adverse events and may be reduced by decreasing the dosage of co-medication. The inhibition of stiripentol by the cytochrome P450 complex (CYP2C19, and CYP3A4 leads to clinically significant interactions. Experimental data, both in vitro and in vivo, have definitively established that stiripentol is a GABAergic anticonvulsant and acts on different sites than benzodiazepines. The pharmacodynamic interactions also

  4. Marijuana Use in Epilepsy: The Myth and the Reality.

    Science.gov (United States)

    Detyniecki, Kamil; Hirsch, Lawrence

    2015-10-01

    Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia. Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts. This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians' and patients' opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.

  5. Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

    Science.gov (United States)

    Hadzik, B; Grass, H; Mayatepek, E; Daldrup, T; Hoehn, T

    2014-09-01

    The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

  6. Effects of eugenol on granule cell dispersion in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Jeong, Kyoung Hoon; Lee, Dong-Seok; Kim, Sang Ryong

    2015-09-01

    Granule cell dispersion (GCD), a structural abnormality, is characteristic of temporal lobe epilepsy (TLE). Eugenol (EUG) is an essential component of medicinal herbs and is suggested to exert anticonvulsant activity. However, it is unclear whether EUG ameliorates the abnormal morphological changes in granule cells induced by epileptic insults. In the present study, we examined whether intraperitoneal injection of EUG attenuated increased seizure activity and GCD following intrahippocampal injection of kainic acid (KA). Our results showed that EUG significantly increased the seizure threshold, resulting in delayed seizure onset, and reduced GCD in KA-induced epilepsy. Moreover, EUG treatment significantly attenuated KA-induced activation of mammalian target of rapamycin complex 1 (mTORC1), which is involved in GCD development, in the dentate gyrus (DG). These results suggest that EUG may have beneficial effects in the treatment of epilepsy through its ability to inhibit GCD via suppression of KA-induced mTORC1 activation in the hippocampal DG in vivo.

  7. Effects of Intravenous Ketamine Infusions in a Neuropathic Pain Patient with Lichen Sclerosus et Atrophicus.

    Science.gov (United States)

    Hanna, Ashraf F; Armstrong, Josh S; Smith, Adam J

    2016-01-01

    A patient reported to the Florida Spine Institute (Clearwater, Fla., USA) with severe lichen sclerosus of the anogenital region and legs. The patient's pain presentation was neuropathic with hypersensitivity, allodynia, swelling, and weakness. The patient had failed multiple pain management modalities including opioid therapy, anticonvulsants, and antidepressants. The patient completed a standard intravenous ketamine infusion regimen developed at the Florida Spine Institute and reported complete abolishment of her pain syndrome. For the first time, we report that ketamine infusions also dramatically improved a patient's lichen sclerosus. That ketamine is known to have immunomodulatory properties, and given the clinical observations described in this case report, suggests that ketamine should be explored as a possible new therapeutic option for managing lichen sclerosus, especially in cases that are refractory to conventional therapies. PMID:27462225

  8. Clinical update: febrile convulsion in childhood.

    Science.gov (United States)

    Paul, Siba Prosad; Blaikley, Sarah; Chinthapalli, Ravindranath

    2012-07-01

    Febrile convulsion is common in young children and occurs in 3-4% of children aged under six years of age. This is the most common seizure disorder and it is not epilepsy. It occurs generally with high temperatures and recurs in one third of children during a subsequent febrile illness. These episodes can be extremely frightening for parents and lot of reassurance needs to be provided by health professionals after an episode. Most often the episodes are short lived and self-terminating and long-term anticonvulsant medicines are not required. The prognosis is generally good and affected children do not suffer any long-term health problems. Community practitioners can provide education, support and counselling to help families return to normality after an event. PMID:22866531

  9. Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

    Science.gov (United States)

    Lintunen, Minnamaija; Sallmen, Tina; Karlstedt, Kaj; Panula, Pertti

    2005-10-01

    Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE.

  10. Vitamin D and systemic lupus erythematosus: an update.

    Science.gov (United States)

    Mok, Chi Chiu

    2013-05-01

    Vitamin D is a steroid hormone that, in addition to its actions on calcium and bone metabolism, exhibits a plethora of regulatory effects on growth, proliferation, apoptosis and function of the cells of the immune system that are relevant to the pathophysiology of systemic lupus erythematosus (SLE). Hypovitaminosis D is highly prevalent in SLE as a result of avoidance of sunshine, photoprotection, renal insufficiency and the use of medications such as glucocorticoids, anticonvulsants, antimalarials and the calcineurin inhibitors, which alter the metabolism of vitamin D or downregulate the functions of the vitamin D receptor. Low levels of vitamin D correlate with disease activity, and is associated with osteoporosis, fatigue and certain cardiovascular risk factors in SLE patients. This review updates the recent evidence on the relationship between vitamin D status and the onset, activity and complications of SLE, and summarizes the recommendations for vitamin D supplementation.

  11. Shellfish Toxins Targeting Voltage-Gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    Fan Zhang

    2013-11-01

    Full Text Available 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 accumulate in marine animals via the food chain. Consumption of shellfish toxin-contaminated seafood may result in potentially fatal human shellfish poisoning. This article provides an overview of the structure, bioactivity, and pharmacology of shellfish toxins that act on VGSCs, along with a brief discussion on their pharmaceutical potential for pain management.

  12. In silico Molecular Docking of Lavandula Angustifolia Mill’s compounds along with a number of antianxiety Drugs with GABAA receptor for reduce stress

    Directory of Open Access Journals (Sweden)

    Ali Kazemi Babaheydari

    2014-06-01

    Full Text Available GABAA receptor is hetero-oligomeric Cl- channel that is elective blocked by the alkaloid bicuculline and modulated by steroids, barbiturates and benzodiazepines. The anticonvulsant activity of Diazepam, Amobarbital and Phenobarbital may be mediated in Section by enhancement of inhibition involving y-aminobutyric acid (GABA. Lavender is one of the maximum effective medicinal plants various therapeutic effects of lavender, so as sedative, spasmolytic, antiviral, and antibacterial activities have been reportage. The molecular docking analyses done indicate the highly and effectively interactions between GABA and the Lavandula angustifolia Mill compounds. Ligand Lavandula angustifolia Mill compounds with GABAA are safer and milder with fewer or no side effects than the drugs currently used in the remedy of lessening high Stress which can be better for the development of new therapeutics to blocked GABAA lessening stress. Results confirm all the Lavandula angustifolia Mill compounds were good binding energy when compared with the binging energies of Diazepam, Amobarbital and Phenobarbital.

  13. Protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model.

    Science.gov (United States)

    Tsuda, T; Sugaya, A; Ohguchi, H; Kishida, N; Sugaya, E

    1997-08-01

    Protective effects of peony root extract and its components on neuron damage in the CA1 area of the hippocampus induced by the cobalt focus epilepsy model were examined. Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were completely prevented when peony root extract was continuously administered orally at 1 g/kg/day for 30 days prior to cobalt application. Component crude gallotannin fraction showed marked but incomplete protective action. A combination of crude gallotannin fraction and paeoniflorin showed complete protective action in the same way as peony root extract against neuron damage although use of paeoniflorin alone had no effect. These findings together with our previous reports indicate that peony root extract and its component, gallotannin, have excellent protective effects on neuron damage in addition to anticonvulsant action by prior oral administration.

  14. Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacológico e usos clínicos

    Directory of Open Access Journals (Sweden)

    Beraldo Heloisa

    2004-01-01

    Full Text Available This article shows that thiosemicarbazones, semicarbazones and their metal complexes can exhibit target selectivity along with a wide pharmacological profile. Complexes of thiosemicarbazones with cytotoxic or antitumoral activity are presented, some of which show activity against cisplatinum-resistant cells. The inhibition mechanism of the enzyme ribonucleoside diphosphate reductase (RDR, involved in DNA syntheses, by alpha(N-heterocyclic thiosemicarbazones is discussed. The encouraging results of clinical trials with the RDR inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone ("Triapine" against rapidly growing tumors are outlined. Examples are also given of thiosemicarbazones with antiviral and antimicrobial activity. The possible applications of semicarbazones as anticonvulsants with low toxicity and good therapeutic index are presented.

  15. Mannich Bases: An Important Pharmacophore in Present Scenario

    Directory of Open Access Journals (Sweden)

    Suman Bala

    2014-01-01

    Full Text Available Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, β-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group.

  16. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Directory of Open Access Journals (Sweden)

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  17. Management and Prevention of Herpes Zoster: A Canadian Perspective

    Directory of Open Access Journals (Sweden)

    Guy Boivin

    2010-01-01

    Full Text Available Varicella-zoster virus reactivation leads to herpes zoster – the main complication of which is postherpetic neuralgia (PHN. Rapid antiviral therapy initiated within 72 h of rash onset has been shown to accelerate rash healing, reduce the duration of acute pain and, to some extent, attenuate the development and duration of PHN. Other adjunctive therapies such as analgesics, antidepressants and some anticonvulsants are frequently required in the management of severe PHN. A live, attenuated zoster vaccine has been recently shown to significantly decrease herpes zoster incidence, PHN and the overall burden of illness when administered to adults older than 60 years of age. This new prophylactic modality has been reported to be cost-effective in the Canadian context, especially in the 60- to 75-year-old age group.

  18. The study on Buthus martensii Karsch

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2002-02-01

    Full Text Available Objective: Through the literatures on the effects of Buthus martensii Karsch, we are finding out the clinical possibility and revealing the more effctive to intractable diseases. Method: We investigated the literatures of Oriental Medicine and experimental reports about Buthus martensii Karsch. Results: 1. The taste of Buthus martensii Karsch is salty, hot and toxic, and the effect of this is tetanus, headache, facial palsy and convulsion. 2. The venom of Buthus martensii Karsch is anaesthetic and toxic protein, composed of buthotoxin, lecithin, trimethylamine, betaine, taurine, cholesterol, stearic acid and palmitic acid and similar to the snake venom. 3. The pharmacological effects ofButhus martensii Karsch are anti-convulsion, depressor, anesthesia, anti-thrombosis and anti-cancer. 4. Symptoms of Buthotoxin poisoning are local pain, vomiting, fever, hypertension and palpitaion, and critical condition to Dyspnea, coma and death.

  19. ANTI-INFLAMMATORY ACTIVITY OF 3-[(5-SUBSTITUED-1, 3, 4 OXADIAZOLE-2-YL METHYL AMINO]-2-METHYL QUINAZOLIN-4(3H-ONES

    Directory of Open Access Journals (Sweden)

    Ramesh Dhani

    2012-12-01

    Full Text Available The process of establishing a new drug is exceedingly complexioned involves the talents of people from a variety of disciplines including Pharmaceutical chemistry, biochemistry, physiology, pharmacology, pharmaceutics and medicine. Quinazolinone is a heterocyclic chemical compound. There are two structural isomers, 2-quinazolinone and 4-quinazolinone, with the 4-isomer being the more common. Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, anti-inflammatory, antihistaminic, anticancer CNS depressant, and so on. All the synthesized quinazolinone derivatives were confirmed preliminarily by M.P and TLC and further all the synthesized compounds were screened for anti-inflammatory activity using Phenyl butazone as the standard and carragennin induced paw oedema model used for anti-inflammatory activity.

  20. Blood concentrations of clobazam and norclobazam in a lethal case involving clobazam, meprobamate and clorazepate.

    Science.gov (United States)

    Pok, Phak-Rop Pos; Mauras, Michel; De Saint Léger, Marie-Noëlle; Kuhlmann, Erika; Charpenel-Durat, Catherine; Navarette, Claudie; Duval, Marie-Laure; De Meo, Pierre

    2010-11-01

    Clobazam is a benzodiazepine with anti-anxiety and anticonvulsant properties marketed in several countries. Norclobazam, a metabolite of clobazam, has similar pharmacological activity but weaker sedative and tranquilizing effect. The two drugs were detected by GC-MS and determined by HPLC-DAD in the samples from a postmortem case. The femoral blood concentrations of clobazam and norclobazam were 0.72 and 36 μg/mL, respectively. The concentration of the active norclobazam was very high. The sum of both clobazam and norclobazam blood concentration (36.72 μg/mL) was clearly toxic, but was not necessarily fatal. Other associated drugs concentrations were within their therapeutic ranges. Interactions due to drug association were discussed. PMID:20870445

  1. Phenprobamate dependence: a case report.

    Science.gov (United States)

    Demir, Bahadir; Demir, Yasemin; Aksoy, Ihsan; Kilic, Osman Hasan Tahsin; Gucyetmez, Volkan; Savas, Haluk A

    2015-06-01

    Phenprobamate (3-phenylpropylcarbamate) is a centrally acting muscle relaxant with mild sedative and anticonvulsant effects. Muscle relaxants can enhance and prolong the effect of narcotic drugs and enable to obtain same effect with a smaller amount of alcohol or illicit substance. Almost all of the centrally acting muscle relaxants have varying sedative effects on which their abuse potential mainly depends. Data related to abuse of carisoprodol, meprobamate, baclofen takes place in the literature. However, to our knowledge this is the first case report about abuse of and tolerance to phenprobamate. We aimed to attract attention to important points of prescribing drugs that have abuse potential like in our case who was using up to 16000 mg/day phenprobamate. PMID:25727392

  2. Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    Chung-Hsing Chou

    2007-01-01

    Full Text Available An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized due to generalized convulsive status epilepticus. Initially, hyperglycemia and ketoacidosis were diagnosed, but his seizures were refractory to the medical treatment. Additionally, a high level of serum theophylline (29.1 mg/mL was detected. Following detoxification of theophylline by oral activated charcoal, the patient regained consciousness and was free from seizures without antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute subdural hematomas at the bilateral occipital hemispheres. This case suggests that theophylline toxicity may be a predisposing factor for seizures in patients with a history of traumatic brain injury in spite of the presence of diabetic ketoacidosis that may have an anticonvulsant action.

  3. Posterior reversible encephalopathy syndrome (pres) in two clinical cases of eclampsia

    International Nuclear Information System (INIS)

    The Posterior Reversible Encephalopathy Syndrome is a neurological condition described on 1996, developed in patients with complex systemic conditions, especially pregnant women with pre eclampsia that at the same time presented neurological signs as seizures, headache, visual loss, and vomiting in addition to posterior brain edema, visible on neuroimaging and located in parietal and occipital lobes, that usually reverses completely. We present two clinical cases with Pres and eclampsia, antenatal and post-partum, both with seizure and confirmed brain edema with Nuclear Magnetic Resonance. Both had a favorable evolution after the anticonvulsant and anti-hypertensive therapy were done. We discuss the controversy over pathophysiological mechanisms, the new methods for diagnosis and management and the importance of multidisciplinary approach

  4. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine;

    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......,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical...... (P pain threshold in the burn area (P =.04) and reduced secondary hyperalgesia, but the reduction was not significant (P =.06). Heat pain thresholds, pain during the burn, and mechanical pain in the area of secondary hyperalgesia were...

  5. Gabapentin induces edema, hyperesthesia and scaling in a depressed patient; a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Reza Bidaki

    2016-01-01

    Full Text Available Gabapentin is a common drug used as analgesic and anticonvulsant and also is prescribed for insomnia, depression, obsessive - compulsive disorder and panic attack. We report a case of a 48-year-old man who is prescribed gabapentin because of insomnia, headache, and depressed mood. In the first period of using the drug no complication has been seen. However in the next period, side-effects such as hyperesthesia, scaling and severe localized edema has been observed. After several laboratory tests and imaging, no reason was found for his edema. And after discontinuing gabapentin the pain and edema was quite relieved. We found out the brand of the drug has been switched in the second stage. The point which makes our study special is the incidence of side-effects such as severe edema, scaling and hyperesthesia for the first time because of using gabapentin and changing the drug combination.

  6. Gabapentin induces edema, hyperesthesia and scaling in a depressed patient; a diagnostic challenge.

    Science.gov (United States)

    Bidaki, Reza; Sadeghi, Zahra; Shafizadegan, Safiye; Sadeghi, Ali; Khalili, Behrang; Haghshenas, Alireza; Mirhosseini, Seyyed Mohammad Mahdy

    2016-01-01

    Gabapentin is a common drug used as analgesic and anticonvulsant and also is prescribed for insomnia, depression, obsessive - compulsive disorder and panic attack. We report a case of a 48-year-old man who is prescribed gabapentin because of insomnia, headache, and depressed mood. In the first period of using the drug no complication has been seen. However in the next period, side-effects such as hyperesthesia, scaling and severe localized edema has been observed. After several laboratory tests and imaging, no reason was found for his edema. And after discontinuing gabapentin the pain and edema was quite relieved. We found out the brand of the drug has been switched in the second stage. The point which makes our study special is the incidence of side-effects such as severe edema, scaling and hyperesthesia for the first time because of using gabapentin and changing the drug combination. PMID:26955622

  7. Synthetic neurosteroids on brain protection

    Institute of Scientific and Technical Information of China (English)

    Mariana Rey; Hctor Coirini

    2015-01-01

    Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disordersvia reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis-tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom-ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl conifguration is the key for binding and activity, but modiifcations in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.

  8. Psychosomatic factors in pruritus.

    Science.gov (United States)

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971

  9. 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;

    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...... for functional characterization of the extracts. The affinity towards the NMDA and the AMPA receptor was investigated using classical [(3)H]-GP39653 and [(3)H]-AMPA binding assays, respectively. RESULTS: The extracts of Searsia dentata and Searsia pyroides inhibited the spontaneous epileptiform discharges...

  10. Modulation of Treg function improves adenovirus vector-mediated gene expression in the airway.

    Science.gov (United States)

    Nagai, Y; Limberis, M P; Zhang, H

    2014-02-01

    Virus vector-mediated gene transfer has been developed as a treatment for cystic fibrosis (CF) airway disease, a lethal inherited disorder caused by somatic mutations in the cystic fibrosis transmembrane conductance regulator gene. The pathological proinflammatory environment of CF as well as the naïve and adaptive immunity induced by the virus vector itself limits the effectiveness of gene therapy for CF airway. Here, we report the use of an HDAC inhibitor, valproic acid (VPA), to enhance the activity of the regulatory T cells (T(reg)) and to improve the expression of virus vector-mediated gene transfer to the respiratory epithelium. Our study demonstrates the potential utility of VPA, a drug used for over 50 years in humans as an anticonvulsant and mood-stabilizer, in controlling inflammation and improving the efficacy of gene transfer in CF airway. PMID:24385144

  11. The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone.

    Science.gov (United States)

    Joukar, Siyavash; Dehesh, Mohammad-Moein

    2015-12-01

    Dry stigmas of the Crocus sativus L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart. This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat. Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated. The heart rate decreased and RR interval increased in Saf200 and Amio groups (Psaffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat. PMID:27329172

  12. Wedelia chinenis (Asteraceae) - An overview

    Institute of Scientific and Technical Information of China (English)

    Sameksha Koul; A Pandurangan; RL Khosa

    2012-01-01

    Objective: The plant Wedelia chinensis (W. chinensis) belonging to family Asteraceae (sunflower family) has great importance in Ayurvedic, Sidhha and Unani systems of traditional medicine. Thorough screening of literature available on W. chinensis depicted the fact that it is a popular remedy among the various ethnic groups, Ayurvedic and traditional practitioners for treatment of various ailments. Extensive studies show presence of flavonoids, diterpenes, triterpene saponins and phytosteroids. W. chinensis is reported to possess antioxidant, anti-inflammatory, analgesic, antimicrobial, hepatoprotective, CNS depressant, anti-osteoporic, anticonvulsant, wound healing, sedative, antistress, antiulcerogenic and anticancer activity. This work gives an overview of the phytochemical and pharmacological evidence of W. chinensis. Although more studies are necessary to explore the therapeutic potential of this plant as, it has more therapeutic properties which are not known.

  13. Quetiapine extended release for the treatment of bipolar disorder.

    Science.gov (United States)

    Samalin, Ludovic; Tremey, Aurore; Llorca, Pierre-Michel

    2014-09-01

    Management of bipolar disorder (BD) requires a complex combination of pharmacological and psychosocial interventions. Over recent decades the therapeutic arsenal for BD has expanded to include lithium, anticonvulsants and second-generation antipsychotics (SGAs). Immediate release (IR) quetiapine fumarate is a SGA approved in several countries for the treatment of patients with schizophrenia and BD or as an add-on treatment for major depressive disorders. Extended release (XR) quetiapine fumarate was developed more recently. There is interest in a once-daily formulation which may improve patient compliance but there may be some differences between quetiapine IR and XR in terms of safety and efficacy. This article provides an update of recent data on the efficacy and safety of quetiapine XR for the treatment of BD. PMID:25096854

  14. Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

    Science.gov (United States)

    Krivoshein, Arcadius V.; Ordonez, Carlos; Khrustalev, Victor N.; Timofeeva, Tatiana V.

    2016-10-01

    α,α-Dialkyl- and α-alkyl-α-aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various α-substituted cyclic imides, lactams, and acetamides were reported, no in-depth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three α,α-diethyl-substituted compounds - 3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide - in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

  15. Does lithium protect against dementia?

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Forman, Julie Lyng; Andersen, Per Kragh

    2010-01-01

    OBJECTIVE: To investigate whether treatment with lithium in patients with mania or bipolar disorder is associated with a decreased rate of subsequent dementia. METHODS: Linkage of register data on prescribed lithium in all patients discharged from psychiatric health care service with a diagnosis...... exposed to lithium (50.4%), 1,781 to anticonvulsants (36.7%), 4,280 to antidepressants (88.1%), and 3,901 to antipsychotics (80.3%) during the study period. A total of 216 patients received a diagnosis of dementia during follow-up (103.6/10,000 person-years). During the period following the second....... Methodological reasons for these findings cannot be excluded due to the nonrandomized nature of the data....

  16. A review of traditional plants used in the treatment of epilepsy amongst the Hausa/Fulani tribes of northern Nigeria.

    Science.gov (United States)

    Muazu, J; Kaita, A H

    2008-01-01

    Five prescriptions used in the treatment of epilepsy amongst the Hausa/Fulani tribe of Northern Nigeria were collected from traditional healers. The five prescriptions containing eight plants were reviewed as in literature to ascertain scientific basis of their use in treatment of epilepsy. Securidaca longipedunculata (family Polygalaceace) was reported to have such property; Mitragyna inermis (family Rubiaceae) has alkaloids structurally similar to clinically useful anticonvulsant. Celtis integrefolia (family Ulmaceae) was reported to contain gamma amino butyric acid (GABA) that its deficiency may lead to convulsions. The remaining plants were basically helpful in alleviation of associated symptoms of epilepsy except Centaurea praecox (family Asteraceae) which was reported to have neurotoxic substances that may worsen the disease. PMID:20161961

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

    Science.gov (United States)

    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 monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy. PMID:20640233

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

    Directory of Open Access Journals (Sweden)

    Matthew D. Krasowski

    2010-06-01

    Full Text Available 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 monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

  19. Posterior reversible encephalopathy syndrome in an AIDS patient with acute renal failure and hypertension

    Directory of Open Access Journals (Sweden)

    Olivia Bargiacchi

    2013-03-01

    Full Text Available Introduction: The posterior reversible encephalopathy syndrome (PRES is a neurological entity characterized by magnetic resonance imaging (MRI evidence of bilateral subcortical edema in the occipital regions of the brain. Case report: We report the case of a female patient with AIDS, pulmonary aspergillosis, CMV infection, and acute renal failure due to Clostridium difficile diarrhea. Her clinical course was complicated by seizures and hypertension. MRI findings were consistent with PRES. The patient was treated with anticonvulsants and antihypertensive agents with clinical improvement. Discussion and conclusions: Few cases of PRES in HIV-infected patients have been described, and it is not clear whether HIV infection is a predisposing factor for this syndrome. The article reviews the literature on PRES in HIV and discusses the role of HIV-associated endothelial damage in the pathogenesis of this syndrome.

  20. Structure-activity relationships of 3-substituted-5,5- diphenylhydantoins as potential antiproliferative and antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Trišović Nemanja

    2011-01-01

    Full Text Available A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 μM, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.