Electroshock Convulsions Research Articles

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

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. 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. 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<0.05) increase in the mean onset of seizure in unprotected animals. The fraction did not exhibit a significant activity against maximal electroshock convulsion. The median lethal dose of the fraction was found to be 1 261.91 mg/kg. 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.

Potentiation of anticonvulsant activity of phenytoin by calcium channel blockers (verapamil and amlodipine) against maximal electroshock seizures in rats

Background: The objective of this work was to study the anticonvulsant activity of calcium channel blockers verapamil and amlodipine and their interaction with an established antiepileptic drug diphenylhydantoin (DPH) in experimental model of epilepsy in albino rats. Methods: Maximal electroshock (MES) convulsions were induced by electroconvulsiometer and different phases of MES were noted in control and drug treated groups. Effect of different doses of verapamil (dose-5, 10 and 15 mg/kg), amlodipine (dose-2.5, 3 and 3.5 mg/kg) and DPH (dose-0.5 and 1 mg/100 g) on MES was studied. Finally, effect of combined treatment consisting of non-protective dose of DPH with different doses of verapamil and amlodipine were also studied on MES induced seizures. Results: Combination of non-protective dose (0.5 mg/100 g) of DPH with all the three doses of verapamil and amlodipine offered significant protection against MES induced seizures. Conclusions: From the present investigation, it may be concluded that the dose of DPH may be reduced in an antiepileptic individual who is on verapamil and amlodipine therapy.

Anticonvulsant Effect of the Essential Oil and Methanolic Extracts of Zataria Multiflora Boiss

Zataria multiflora is an Iranian endemic plant with a variety of uses. Anticonvulsant effect of the plant has not been studied yet. We aimed to evaluate the anticonvulsant effect of the essential oil and methanolic extract of the plant on chemical and electrically seizures. Essential oil (EO) and methanolic extract (ME) were prepared by hydrodistillation and maceration method respectively and administered for evaluating the anticonvulsant activity against pentylenetetrazole (PTZ) and maximal electroshock (MES) convulsions in mice. Different doses of the EO and ME of Zataria multiflora were administered intraperitoneally (i.p), thirty minutes before induction of chemical (PTZ, 100 mg/kg) and electrical (50 mA, 50 Hz, 1 s duration) convulsions. Neurotoxicity was evaluated using rota-rod test. Mortality was determined after 24 hours for determining LD50. EO significantly increased the onset time of clonic seizures at doses of 0.2, 0.25 and 0.35ml/kg and significantly prevented tonic convulsions induced by PTZ at the same doses. No increase in onset time of tonic convulsions was observed. Methanolic extract of Z. multiflora was not effective in PTZ model. Neither EO nor ME was effective against MES convulsions; however both of them significantly reduced the time spent on rota-rod at doses of 0.6 ml/kg and 3 g/kg respectively. LD50 value of the EO was determined as 1.30 (1.0-1.5) ml/kg. No mortality was seen for the ME until dose of 5 g/kg. EO would be a good candidate for more investigations to determine its active constituent(s) and also its mechanism against PTZ-induced seizures.

The effects of apomorphine, (+)-amphetamine and L-dopa on maximal electroshock convulsions--a comparative study in the rat and mouse.

Abstract The anticonvulsant activity of apomorphine, (+)-amphetamine and pargyline + l-dopa was examined in the rat and mouse. Whereas all three treatments produced anticonvulsant effects in the rat, only (+)-amphetamine and l-dopa were anticonvulsant in the mouse. It is suggested that enhanced dopamine-like activity is responsible for the anticonvulsant activity of these three drugs in the rat. The anticonvulsant activity of (+)-amphetamine and l-dopa in the mouse may be unrelated to their pharmacological activity on dopaminergic neurons.

Neuropharmacological activity of Lippia nodiflora Linn.

Introduction:In the recent years, plants containing flavonoids have gained much more interest in research area, as they are found to be specific ligands for benzodiazepine receptors.Material and Methods:In our investigation, we evaluated the neuropharmacological profile of petroleum, chloroform and ethanolic extracts of aerial part of Lippia nodiflora Linn. With experimental models using test such as potentiation of diazepam-induced sleeping time, locomotor activity, motor coordination, exploratory behavior pattern, elevated plus maze and maximal electroshock convulsions. Diazepam at doses of 5, 4, and 1 mg/kg served as standard.Results:Results showed that the ethanolic extract of L. nodifl ora at both doses (250 and 500 mg/kg p.o.) and its chloroform extract at a higher dose of 500 mg/kg produced central inhibitory (sedative) effects, anticonvulsant effect and anxiolytic effect in mice. Values were statistically significant (P < 0.05 and P < 0.01) when compared to the control group. The petroleum ether extract of plant at both dose levels (250 and 500 mg/kg p.o.) did not produce any central effects.Conclusion:In conclusion, we can say that the ethanolic and chloroform extracts showed the central inhibitory activity due to the presence of fl avonoids and this fact was also supported by the finding that the petroleum ether extract did not show any central effect and flavonoids were not found in it.

Anti-convulsant activity of aqueous and alcohol extracts of roots and rhizomes of Nymphoides indica (L.) Kuntze in Swiss albino mice.

Nymphoides indica (L.) Kuntze (Menyanthaceae) is an aquatic herb used as an admixture along with Nymphoides macrospermum and as a substitute of Ayurvedic drug Tagara ( Valeriana jatamansi Jones) in the treatment of various diseases like epilepsy, anemia, jaundice, tuberculosis to name a few. The present study has been undertaken to evaluate the anti-convulsant effect of aqueous and alcohol extract of roots and rhizomes of Nymphoides indica (L.) Kuntze using Maximum Electroshock Convulsion (MES) and Pentylenetetrazole (PTZ) induced convulsion methods in swiss albino mice. The oral administration of alcohol and aqueous extracts at the dose level of 300 and 600 mg/kg reduced duration of extensor phase (HLTE) and time taken for recovery in MES induced convulsion model. Similarly both extracts delayed onset of convulsions and reduced the time taken for recovery in PTZ induced convulsions. Alcohol extract was found to be more effective and effect of alcohol and aqueous extract on extensor phase (HLTE) (MES) and onset of convulsions (PTZ) was dose dependent. It is concluded that roots and rhizomes of N. indica exhibit anticonvulsant activity, justifying its use as a substitute of Tagara (V. jatamansi ) in treatment of epilepsy.

New morphinan derivatives with negligible psychotropic effects attenuate convulsions induced by maximal electroshock in mice

Interest in dextromethorphan (DM) has been renewed because of its anticonvulsant and neuroprotective properties. However, DM at supra-antitussive doses can produce psychotomimetic effects in humans. Recently, we demonstrated that DM exerts psychotropic effects in mice [Neurosci. Lett. 288 (2000) 76, Life Sci. 69 (2001) 615]. We synthesized a series of compounds with a modified morphinan ring system, with the intention of developing compounds that retain the anticonvulsant activity with weak psychotropic effects [Bioorg. Med. Chem. Lett. 11 (2001) 1651]. In order to extend our understanding of the pharmacological intervention of these morphinans, we assessed their behavioral effects, and then examined whether they exert protective effects on maximal electroshock convulsions (MES) in mice. Repeated treatment (20 or 40 mg/kg, i.p./day × 7) with DM or dextrorphan (a major metabolite of DM; DX) significantly enhanced locomotor activity in a dose-related manner. This locomotor stimulation was accentuated more in the animals treated with DX, and might be comparable to that of phencyclidine (PCP). By contrast, treatment with a metabolite of DM [3-methoxymorphinan (3MM) or 3-hydroxymorphinan (3HM)], 3-allyloxy-17-methylmorphinan (CPK-5), or 3-cyclopropylmethoxy-17-methylmorphinan (CPK-6) did not significantly alter locomotor activity or patterns. The behavioral effects mediated by these morphinans and PCP paralleled the effects of conditioned place preference. DM, DX, CPK-5, and CPK-6 had anticonvulsant effects against MES, while 3MM and 3HM did not show any anticonvulsant effects. We found that DM, DX, CPK-5 and CPK-6 were high-affinity ligands at σ 1 receptors, while they all had low affinity at σ 2 receptors. DX had relatively higher affinity for the PCP sites than DM. By contrast, CPK-5 and CPK-6 had very low affinities for PCP sites, suggesting that PCP sites are not requisites for their anticonvulsant actions. Our results suggest that the new morphinan analogs are promising anticonvulsants that are devoid of PCP-like behavioral side effects, and their anticonvulsant actions may be, in part, mediated via σ 1 receptors.

Anticonvulsive and neurotoxic effects of lamictal (lamotrigine) in combination with other anticonvulsive preparations

In the model of electroshock convulsions combined administration of lamictal with other anticonvulsants (sodium valproate, phenobarbital, Diphenine, carbamazepine, ethosuximide, diazepam, and riodipin) decreased ED50 of each preparation by 1.9–4.2 times. The effectiveness of combination with carbamazepine was the highest: its therapeutic index was higher than that of each ingredient preparation.

Effectiveness of combined application of calcium blockers and antiepileptic drugs

Using the model of electroshock convulsions, we showed that combined administration of blockers of potential-operated (riodipine and nifedipine) or receptor-activated (MK-801) calcium channels with the antiepileptics sodium valproate, phenobarbital, diazepam, ethosuximide, carbamazepine, and Diphenine markedly reduces drug doses and increases therapeutic index of their combinations.

Anti-convulsion effects of choto-san and chotoko (Uncariae Uncis cam Ramlus) in mice, and identification of the active principles

The crude drug, Chotoko (Uncariae Uncis cam Ramlus), the hooks of Uncaria spp. (Rubiaceae), has been claimed to possess sedative and anti-spasmodic actions, and is contained in a Chinese traditional preparation, Choto-san, as a main crude drug. Examinations were made on the anti-convulsion effects of Choto-san and Chotoko against some animal models of epilepsy conducted by the stimulation of drugs or electricity. Oral administration of the Choto-san extract to mice at the doses of 1.0 g/kg and 3.0 g/kg tended to inhibit the glutamate-induced convulsion in a dose-dependent manner, and the effect of the Chotoko extract at a 3.0 g/kg dose was significant, while both the extracts showed no activity against the picrotoxine-induced, strychinine-induced, and electroshock convulsions. The Choto-san preparation without Chotoko was inactive, and the activity of the Chotoko extract was more potent than that of the every crude drug comprising Choto-san, suggesting that Chotoko plays the most important role in the Choto-san prescription and contains some active compounds. Bioassay-guided fractionation of the Chotoko extract led to the location of the active components in the less polar alkaloids-containing fraction, from which three indole alkaloids, geissoschizine methylether (1), hirsuteine (2) and hirsutine (3), and an oxyindole alkaloid, isocorynoxeine (4) were isolated and identified. Oral administration of 1 and 2 to mice at the doses of 50, 100, and 200 mg/kg inhibited the glutamate-induced convulsion in a dose-dependent manner. The effect of 3, the dihydro derivative of 2, was less potent than those of 1 and 2. Compound 4 showed no activity at a 100 mg/kg dose compared with control. The above results support the Chinese herbal description of the anti-spasmodic action of Chotoko, and show that 1 and 2 contained in Chotoko must be mainly contributed to the activity. It is also suggested that Choto-san may be clinically available for treatment of epilepsy.

Does a history of convulsions increase the amnestic effect of temporal region brain lesions?

Rats with surgical lesions of the hippocampal formation, amygdala, and nearby neocortex and pyriform cortex were impaired on a swim-to-platform test and on a passive avoidance test. These impairments were not increased by presurgical treatment with a series of 21 electroshock convulsions. To the extent that this rat preparation can be compared with human patients, the data suggest that a previous history of epileptic seizures does not increase the amnestic effect of temporal lobe lesions.

Structure-activity study on anticonvulsant (thio) hydantoins using molecular connectivity indices.

The relationship between molecular connectivity indices and anticonvulsant activity of a series of hydantoin/thiohydantoin analogs has been investigated. The values of molecular connectivity index and valence molecular connectivity index of 82 compounds were computed and active ranges were identified. The activity assigned to each analog using these topological descriptors was subsequently compared with the reported activity against maximal electroshock convulsions. Predictions with high degree of accuracy were observed using these indices.

The competitive NMDA antagonist, D-CPP-ene, potentiates the anticonvulsant activity of conventional antiepileptics against maximal electroshock-induced seizures in mice

D-CPP-ene [3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid; a competitive antagonist of N- methyl- D- aspartic acid] in a dose of 2 mg kg (i.p.) significantly increased the threshold for electroconvulsions. When given in a dose half that affecting the electroconvulsive threshold, D-CPP-ene potentiated the anticonvulsant activity of carbamazepine, diazepam, diphenylhydantoin, phenobarbital and valproate against maximal electroshock (50 mA)-induced seizures in mice. However, this NMDA antagonist did not influence the plasma levels of the antiepileptic drugs studied, so a pharmacokinetic interaction, in terms of total plasma levels at least, is not probable. The chimney test and retention testing in mice revealed that the combined treatment of D-CPP-ene at 1.0 mg kg (i.p.) with either diazepam, diphenylhydantoin, phenobarbital or valproate (providing a 50% protection against maximal electroshock convulsions) resulted in motor impairment and caused impairment of long-term memory. On the other hand, a combination of D-CPP-ene and carbamazepine was devoid of adverse effects. It can be concluded that the potential utility of D-CPP-ene in combination with conventional antiepileptic drugs does not seem promising, except for carbamazepine.

Anticonvulsive effects of inhaling lavender oil vapour.

In the present experiment, we found that inhaling lavender oil vapour blocked pentetrazol-and nicotine-induced convulsion and electroshock convulsion in mice.

Anticonvulsant effect of fluoxetine on focally evoked limbic motor seizures in rats.

Fluoxetine was evaluated for anticonvulsant effects in a rat model of focally evoked complex partial seizures (CPS) secondarily generalized. Fluoxetine was administered intraperitoneally (i.p.) 1 h before seizures were induced by focal intracerebral application of the GABAA receptor antagonist, bicuculline methiodide (118 pmol) unilaterally into a discrete epileptogenic site in the deep prepiriform cortex ("area tempestas," AT) of rats. Significant dose-dependent protection from clonic motor seizures was obtained after 5-, 10-, and 20-mg/kg doses of fluoxetine, with 50% protection occurring after the 5-mg/kg dose. Suppression of electrographic seizure activity was concomitant with suppression of motor seizures. These observations support and extend previous findings of other investigators who showed that fluoxetine exerts anticonvulsant actions against maximal electroshock (MES) convulsions and audiogenic convulsions in genetically seizure-prone rodents.

Infusion of bicuculline methiodide into the tectum: model specificity of pro- and anticonvulsant actions

Microinjection of drugs, such as muscimol, into the substantia nigra pars reticulata (SNpr) can inhibit several types of experimental seizures. Some findings suggested that this was a result of disinhibition of neurons receiving input from GAB Aergic nigrotectal cells. Indeed, it was reported that bicuculline methiodide (BMI), infused into the tectal region that was reported to receive nigral input, produced an anticonvulsant effect against maximal electroshock (MES) convulsion. Since previous work had suggested that the anticonvulsant effect of intranigral muscimol depended on the particular experimental seizure used, three different experimental seizures were used in the present study to evaluate the effects of BMI infusion into the tectum. Guide cannulas aimed at the tectal region receiving nigral innervation were stereotaxically implanted in rats a week before testing. Bilateral intratectal infusions of BMI (25 ng/ side) had an anticonvulsant effect against MES convulsions, confirming a previous report. In contrast, the same BMI pretreatment worsened convulsions produced by either systemic pentylenetetrazol (40 mg/kg i.p.) or bicuculline (0.5 mg/kg i.V.). The effects of intratectal BMI were seizure model-dependent, suggesting different functional interconnections between tectum and those pathways responsible for generalization of MES as compared to PTZ or bicuculline convulsions.

Effects of postnatal electroshock convulsions on epileptogenesis of the amygdala and hippocampus in adult rats.

Adult rats which received repeated electroshock convulsions (ESCs) during postnatal development underwent electrical kindling of the amygdala (AM) and hippocampus (HIPP). Completion of kindling, especially AM kindling, was significantly faster in the groups with ESCs from the neonatal to late infantile age than in the control group. It is discussed that especially the late infantile age in the postnatal development was supposed to play an important role in the faster kindling brought about by postnatal convulsions and that the faster kindling was due in part to abbreviation of the partial seizure process. However, the neonatal ESC group showed significantly delayed completion of HIPP kindling.

The Influence of Adenosine Receptor Antagonists Ahinophylline (AMP) and Caffeine (CAF) on Seizure Protective Ability of Antiepileptic Drugs (AEDs) in Rats

Abstract The acute effects of AMP and CAF on seizure protectivity of AEDs were examined against electro and chemo shock convulsions in rats. The results support the claim that adenosine receptors may be involved in action of some AEDs.

Effects of Dextromethorphan, a Nonopioid Antitussive, on Development and Expression of Amygdaloid Kindled Seizures

The effects of dextromethorphan (DM), a nonopioid antitussive and a functional N-methyl-D-aspartate (NMDA) antagonist, on expression and development of amygdaloid kindled seizures were examined. The maximum anticonvulsant effect of DM (30 mg/kg) on fully kindled seizures appeared within 30 min of administration and lasted for at least 2 h. DM decreased, in a dose-dependent manner [10-70 mg/kg, intraperitoneally (i.p.)], the severity of kindled seizures 30 min after injection, but the estimated ED50 was 3 times higher than the previously reported value for maximal electroshock convulsions. Furthermore, the high dose (70 mg/kg), while suppressing kindled seizures, produced myoclonus which coincided with EEG spike activity in the amygdala and the cortex. When tested on the development of kindling, 30 mg/kg DM retarded the growth of afterdischarge in the amygdala and the cortex, but had no effect on the development of behavioral seizures. DM 60 mg/kg accelerated development of kindling and produced spontaneous seizures. These results indicate that DM, unlike other NMDA antagonists, has a narrow therapeutic window as an anticonvulsant on kindled seizures and that higher doses may potentiate the kindling process.

Differential prostaglandin formation induced by convulsion in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation

Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D 2 and E 2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD 2 and PGE 2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD 2 synthesis in DBA2 mice diappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE 2 formation persisted. These results suggest that a deficiency of cerebral PGD 2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsion, acoustically induced seizure of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.