Strychnine-induced Seizures Research Articles

Anticonvulsant, Antimicrobial and Cytotoxic Activities of <i>Berberis calliobotrys</i> Aitch ex Koehne (Berberidaceae)

Purpose: To evaluate the anticonvulsant, antimicrobial and cytotoxic activities of Berberis calliobotrys . Methods: The powdered plant material (10 kg) was extracted thrice with methanol (3 × 12 L) by dipping for seven days. The methanol extract was concentrated to dryness under reduced pressure, and then successively fractionated with solvents of different polarity, including n-hexane, chloroform, ethyl acetate and n-butanol. The anticonvulsant effect of the extract and fractions (at oral doses 500 and 1000 mg/kg) was studied against picrotoxin-, pentylenetetrazole (PTZ)- and strychnine-induced seizures in Swiss albino mice of either sex divided into 12 groups (n = 6). Diazepam was used as standard drug. Antimicrobial activity of the extract against Bacillus subtilis , Pseudomonas aeruginosa , Staphylococcus aureus as well as against Candida albicans , Penicillium notatum was conducted by disc diffusion method and minimum inhibitory concentration (MIC). Cytotoxicity of the extract/fractions was analyzed by haemolytic method while the phenolic compounds present in the ethyl acetate fraction of the plant were determined by high performance liquid chromatography (HPLC). Results: The extract and its ethyl acetate and n-butanol fractions showed maximum response against drug-induced convulsions and provided 100 % protection to animals at both doses. They also showed zones of inhibition of 27.00 ± 2.51, and 22.00 ± 2.51 mm against all bacterial and fungal strains, respectively, especially Staphylococcus aureus . The methanol extract and ethyl acetate fraction also showed high MIC against all bacterial and fungal strains. Cytotoxicity data from hemolytic assay indicate that the extract/fractions are safe. The highest amount of phenolic found was chlorogenic acid (84.44 ± 0.06 ppm). Conclusion: The plant is thus a potential source of new lead compounds for the development of new clinically effective anticonvulsant and antimicrobial compounds. Keywords: Berberis calliobotrys , Anticonvulsant, Antimicrobial, Haemolytic, Phenolics, Chlorogenic acid

Evaluation of anticonvulsant effects of methanolic extract of <i>Olax subscorpioidea</i> Oliv. leaves in chicks and mice

Preparations of Olax subscorpioidea have been used in the Nigerian traditional medicine for the management of convulsions, mental illness, pains, cancer and microbial infections. The efficacy of the leaves of this plant in management of convulsions has been widely acclaimed among the Igala communities of North-Central part of Nigeria and therefore, this study was aimed at examining the anticonvulsant effects of methanolic extract of O. subscorpioidea (MEOS) leaves in order to provide scientific basis for its use in management of convulsions. Phytochemical screening and evaluation of intraperitoneal median lethal dose of the extract was carried out. Anticonvulsant activity of MEOS was evaluated in chicks using maximal electroshock test, and in mice using pentylenetetrazole and strychnine-induced seizure models at doses of 100, 200 and 400 mg/kg. The intraperitoneal median lethal dose of MEOS was estimated to be 3800 mg/kg body weight in mice. MEOS at doses of 100 and 200 mg/kg provided 30 and 70% protection against maximum electroshock induced seizures respectively. The extract also significantly (p < 0.05) increased the mean latency to seizures in a dose dependent manner. MEOS at 100 mg/kg provided 50% protection against strychnine-induced seizures. A significant increase (p < 0.01) and (p < 0.05) in the mean onset of strychnine-induced seizures was also observed with MEOS at doses of 200 and 400 mg/kg respectively. These findings suggest that the methanolic extract of Olax subscorpioidea leaves possess anticonvulsant activity. Keywords : Anticonvulsant, Maximal Electroshock, Olax subscorpioidea , Pentylenetetrazole, Strychnine

Evaluation of anticonvulsant and neuroprotective effects of camel milk in strychnine-induced seizure model

ObjectiveTo discover the use of camel milk as an alternate medicine for the treatment and prevention of convulsions using strychnine-induced seizure model. MethodsThirty animals were divided into three equal groups. Group I was on distilled water, Group II was on camel milk for 15 days prior to experiment and Group III was on reference drug diazepam. On the day of experiment, strychnine was administered in all treatment groups after distilled water, camel milk and diazepam treatments respectively. Animals were observed for 30 min for latency of seizure onset, frequency of convulsions and duration of jerks. The mortality rate was also evaluated for each group. ResultsCamel milk treatment showed significant seizure protection as observed by delayed seizure onset (P ≤ 0.001), decreased total duration of convulsions (P ≤ 0.001) and mortality rate (P ≤ 0.001) when compared with Group I. ConclusionsAnticonvulsant activity of camel milk could be due to potentiation of glycinergic and GABAergic activities both. Antioxidant activity can also amplify its antiepileptic activity. Further studies are required to confirm the exact mechanism of action.

Evaluation of neuropharmacological effects of aqueous leaf extract of Albizia glaberrima (Leguminosae) in mice

Ethnopharmacological relevanceAlbizia glaberrima is a shrub found in the deciduous forest and jungle of the coastal plain of West Africa. Preparations of the plant are used traditionally in the treatment of fever, pain and central nervous system disorders, including epilepsy. This study was conducted to investigate the neuropharmacological effects of the aqueous leaf extract of Albizia glaberrima in mice. Materials and methodsThe hole-board, elevated plus-maze, thiopentone-induced sleep (anxiolytic/sedative-hypnotic), traction, climbing, inclined screen (muscle relaxant), strychnine-, picrotoxin- and pentylenetetrazole (PTZ)-induced convulsion (anticonvulsant) tests were employed in this study. ResultsAlbizia glaberrima extract at 200mg/kg significantly increased the duration of head dips (p<0.05) and number of open arms entry (p<0.01) compared with control in the hole-board and elevated plus-maze tests, respectively. At 400mg/kg, Albizia glaberrima extract significantly reduced the number of sectional crossings relative to control. The extract at 400mg/kg significantly (p<0.05) increased the duration of sleep compared with control in the thiopentone-induced hypnosis test. Albizia glaberrima extract at 200mg/kg and diazepam (5mg/kg) significantly (p<0.05, 0.01) increased the post-treatment climbing time and reduced the latency to slide down in the climbing and inclined screen tests, respectively. The extract was not effective in the strychnine-induced seizure model, while in the picrotoxin test Albizia glaberrima extract at 100mg/kg significantly (p<0.05) reduced the duration of convulsion while reducing mortality at 400mg/kg, as was the case with diazepam (2mg/kg). The extract and diazepam significantly (p<0.01, 0.001) increased onset and reduced duration of convulsion, with significant level of protection against convulsion and reduction in mortality in the PTZ-induced seizure model. Preliminary phytochemical screening of the extract revealed the presence of phenols>tannins>saponins>flavonoids. The extract was found to be relatively non-toxic when administered p.o. up to 5000mg/kg and the LD50 was 398.11mg/kg when administered i.p. ConclusionsThe aqueous leaf extract of Albizia glaberrima possesses dose-dependent anxiolytic/muscle relaxant (low dose) and sedative-hypnotic/anticonvulsant (high dose) activities possibly mediated via enhancement of GABAergic inhibitory actions.

CNS activity of leaves extract of Calotropis gigantea

ObjectiveTo study central nervous system activity of ethanolic extract of leaves of Calotropis gigantea (C. gigantea) (Asclepiadaceae), such as anticonvulsant, sedative and muscle relaxation activity. MethodsThe ethanolic extract of C. gigantea administered orally in experimental animals at different doses 100, 200 and 500 mg/kg body weight. The anticonvulsant properties were studied on maximal electroshock test and strychnine-induced convulsions model. Sedative property studied using actophotometer and skeletal muscle relaxant property studied using rota rod. ResultsThis extract protected rats against maximal electroshock induced seizures, but had no or a moderate effect only against strychnine-induced seizures. Locomotor activity in mice found to be decreased and motor coordination was also decreased. The acute toxicity study revealed safely of the extract up to a dose of 2 000 mg/kg. ConclusionsWith these effects, the leaves of C. gigantea possess anticonvulsant sedative and muscle relaxant effect that might explain its use as a traditional medicine.

037 — (LIM0148) Proconvulsant activity of imipenem in the strychnine-induced seizure model in mice

037 — (LIM0148) Proconvulsant activity of imipenem in the strychnine-induced seizure model in mice

048 — (MEN0070) Anticonvulsant activity of acute treatment with manidipine in picrotoxin and strychnine-induced seizure models in mice

048 — (MEN0070) Anticonvulsant activity of acute treatment with manidipine in picrotoxin and strychnine-induced seizure models in mice

Psychopharmacological properties of saponins from Randia nilotica stem bark

Context: Decoctions of Randia nilotica Stapf. (Rubiaceae) have been used in the Nigerian traditional medicine for the management of epilepsy, anxiety, depression and psychosis for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria.Objective: The aim of this study is to establish whether the saponins present in R. nilotica are responsible for its acclaimed beneficial effects in Nigerian traditional medicine.Materials and methods: The behavioural properties of the saponin-rich fraction (SFRN) of R. nilotica stem bark were studied on hole-board, diazepam-induced sleep, rota-rod and beam-walking in mice. The anticonvulsant properties of SFRN were also examined on maximal electroshock, pentylenetetrazole- and strychnine-induced seizures in mice.Results: The intraperitoneal LD50 of SFRN in mice and rats were estimated to be 11.1 and 70.7 mg/kg, respectively. SFRN significantly prolonged the duration of diazepam-induced sleep; diminished head dip counts in the hole-board test and protected mice against maximal electroshock seizures. SFRN failed to protect mice against pentylenetetrazole- and strychnine-induced seizures; and had no effect on motor coordination on the rota-rod treadmill at the doses tested. SFRN significantly decreased the number of foot slips in the beam-walking assay in mice with no effect on time to reach the goal box.Discussion and conclusion: This study provides evidence of the psychopharmacological effects of SFRN, thus supporting further development of the psychoactive components as remedies for epilepsy.

Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures.

Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.

The effects of the Brazilian ant Dinoponera quadriceps venom on chemically induced seizure models

Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5mg/kg) increased the time until the first seizure and the percentage of survival (155.4±27.7s/12.5%, p<0.05) compared to the control group (79.75±3.97s/0%), whereas endovenous treatment (0.1 and 0.5mg/kg) decreased the time until the first seizure (0.1mg/kg: 77.83±5.3s versus 101.0±3.3s in the control group; 0.5mg/kg: 74.43±3.9s versus 101.0±3.3s for the control group, p<0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the D. quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.

Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.)

This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L.) as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L.), using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle), standard (diazepam) and test (Trachyspermum ammi (L.) extract). Trachyspermum ammi (L.) demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L.) and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L.) showed antiepileptic activity, which may be due to the presence of thymol.

Anticonvulsant activity of the methanolic extract of Justicia extensa T. Anders

Ethnopharmacological relevanceTo investigate the anticonvulsant activity of the leaf extract of Justicia extensa T. Anders used traditionally in the treatment of convulsion. Materials and methodsThe anticonvulsant activity of the methanolic extract of Justicia extensa (50, 100 and 200mg/kg, p.o.) was assessed in strychnine-induced (STR) and picrotoxin-induced (PCT) convulsion models in mice. Diazepam (1mg/kg) and phenobarbitone (2mg/kg) were used as reference drugs respectively. ResultsThe extract showed no toxicity and significantly prolonged (p<0.01–0.05) the onset and reduced the duration of the seizures induced by picrotoxin (5mg/kg, i.p.) in a dose dependent manner. Phenobarbitone completely inhibited the seizures in this model. Similarly, in the seizures induced by strychnine (1mg/kg, i.p.), the extract also prolonged the onset and reduced the duration of the seizures though not in a dose dependent manner. Diazepam failed to inhibit the strychnine-induced seizures. The plant extract however showed a significantly higher anticonvulsant activity at 100 and 200mg/kg in comparison with diazepam. ConclusionsThe results obtained from this work suggest that Justicia extensa has anticonvulsant activity and this supports the use of the plant traditionally in the treatment of convulsion.

Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice

Root bark of Nauclea latifolia Smith (Rubiaceae) was evaluated for its anticonvulsant, anxiolytic, and sedative activity in mice. Animal models (maximal electroshock-, pentylenetetrazol-, and strychnine-induced convulsions; N-methyl- d-aspartate-induced turning behavior; elevated plus maze; stress-induced hyperthermia; open field; and diazepam-induced sleep) were used. The decoction from the bark of the roots of N. latifolia strongly increased the total sleep time induced by diazepam. It also protected mice against maximal electroshock-, pentylenetetrazol-, and strychnine-induced seizures. In addition, turning behavior induced by N-methyl- d-aspartate was inhibited. N. latifolia antagonized, in a dose-dependent manner, stress-induced hyperthermia and reduced body temperature. In the elevated plus maze, N. latifolia increased the number of entries into, percentage of entries into, and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. In the open field test, N. latifolia increased crossing and reduced rearing and defecation. It could be concluded that the decoction of N. latifolia, used in traditional medicine in Cameroon in the treatment of fever, malaria, insomnia, anxiety and epilepsy seemed to possess, sedative, anticonvulsant, anxiolytic and antipyretic properties in mice.

Central action of Araucaria angustifolia seed lectin in mice

Possible central nervous system effects of the gymnosperm lectin from Araucaria angustifolia seeds were studied in seizure and open field tests. Male Swiss mice were administered saline (control), lectin (0.1, 1, and 10 mg/kg), flumazenil (1 mg/kg), or diazepam (1 mg/kg) intraperitoneally. Lectin at the highest dose increased time to death in the pentylenetetrazole- and strychnine-induced seizure models as compared with control, but not in the pilocarpine model. In the open field test, lectin reduced locomotor activity at all doses tested, as did diazepam, when compared with control. These locomotor effects were reversed by flumazenil pretreatment. In conclusion, A. angustifolia lectin had a protective effect in the pentylenetetrazole- and strychnine-induced seizure models, suggestive of activity in the GABAergic and glycinergic systems, respectively, and also caused a reduction in animal movements, which was reversed by flumazenil, pointing to a depressant action mediated by a GABAergic mechanism.

Anticonvulsant properties of saponins from Ficus platyphylla stem bark

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.

Anticonvulsant activity of hydroalcoholic extracts from Erythrina velutina and Erythrina mulungu

The anticonvulsant effects of hydroalcoholic extracts (HAEs) from the stem bark of Erythrina velutina and Erythrina mulungu on pentylenetetrazole (PTZ) and strychnine-induced seizure tests and the potentiation of pentobarbital-induced sleeping time in mice with the extracts were examined in this study. These medicinal plants belong to the Fabaceae family and are popularly used in Brazil for their effects on the central nervous system. The extracts of Erythrina velutina (intraperitoneally or orally) and Erythrina mulungu (intraperitoneally) were administered in mice at single doses (200 or 400 mg/kg). While Erythrina velutina and Erythrina mulungu did not exhibit any protector effect in PTZ-induced seizures, at any dose, an increase in the latency of convulsion and in the death time was observed with both doses and routes of Erythrina velutina and at higher dose of Erythrina mulungu, in strychnine-induced seizure. No alteration was observed with Erythrina velutina and Erythrina mulungu on sleeping latency at both doses as compared to control (362.8 ± 59.5). However, the sleeping time was increased in both plants as compared to control (943.8 ± 129.6). In conclusion, we showed that the hydroalcoholic extracts of Erythrina velutina and Erythrina mulungu have anticonvulsant effects only in the strychnine-induced seizure model, suggesting their possible action in glycine system and a potentiation of pentobarbital sleeping time, suggesting depressant action in the central nervous system.

2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures: Synthesis and pharmacological evaluation

Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. Nine compounds exhibited protection in all the three seizure models, and N 1-(2,4-dimethoxyphenyl)- N 4-(propan-2-one)semicarbazone ( 17) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate γ-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam.

CNS depressant activity of Lecaniodiscus cupanioides

The aqueous root extract of Lecaniodiscus cupanioides was used to study the central nervous system depressant activity pattern of the plant. The extract protected mice from strychnine-induced convulsion at 400 mg/kg p.o. and 100 mg/kg i.p. A dose-dependent prolongation of seizure latency was produced at 400 mg/kg, p.o. and 100 mg/kg i.p. for strychnine-induced seizure; and at 400 mg/kg p.o. and 100 mg/kg i.p. for picrotoxin-induced seizure. Moreover, the CNS depressant activity of the extract (200 mg/kg p.o. and 50 mg/kg i.p.) was demonstrated by a significant prolongation of 40 mg/kg, pentobarbitone sleeping time, and significant reduction in exploratory behavior of mice at a dose of 400 mg/kg p.o., with both effects comparable to effects produced by 4 mg/kg chlorpromazine. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity; however, acute (24 h) i.p toxicity test produced a dose-dependent mortality with LD 50 of 455.2 mg/kg.

Stimulated Release of Exogenous GABA and Glutamate from Cerebral Cortical Synaptosomes and Brain Slices by Bis(acetato)tetrakis(imidazole) Copper(II) Complex

In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 microM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1-2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent results can explain the anticonvulsant activity of Cu(OAc)2(Im)4 against strychnine-induced seizures by increasing the net release of GABA from cortical neurons.

Anticonvulsant activity of Mimosa pudica decoction

The decoction of Mimosa pudica leaves given intraperitoneally at dose of 1000–4000 mg/kg protected mice against pentylentetrazol and strychnine-induced seizures. M. pudica had no effect against picrotoxin-induced seizures It also antagonized N-methyl-d-aspartate- induced turning behavior. These properties could explain its use in African traditional medicine.