Strychnine-induced Convulsions Research Articles

Synthesis and Pharmacological Evaluation of Few 2-(Substituted Aryl)-4-(Heteroaryl)-2,3-Dihydro-1h-1,5-Benzodiazepine Derivatives

Benzodiazepines represent a class of privilege scaffold in the modern era of medicinal chemistry as central nervous system active agents. The present work reported synthesis of a series of 2-(substituted aryl)-4-(heteroaryl)-2,3- dihydro-1H-1,5-benzodiazepines. Structural characterization of title compounds was done by using analytical techniques such as IR and 1H-NMR. An acute toxicity study was done to determine the LD50 of the compounds. The compounds were subjected to pharmacological studies to evaluate anticonvulsant potential in mice by strychnine-induced convulsions method. The pharmacological evaluation of the compounds showed an increase in latency (onset time) to induce convulsions and a decrease in convulsions compared to control. The compounds B3, B6 and B8 showed the highest percentage protection as 80% with latency to induce convulsions as 6.46, 6.35 and 6.12 minutes, respectively compared to control at 3 mg/kg. The structural features analysis revealed that the phenyl ring’s second position substituted with halogen, hydroxy group of 2-(substituted phenyl)-4-(furan-2-yl/ thiophene-2-yl)-2,3-dihydro-1H-1,5-benzodiazepine enhanced the anticonvulsant potential of the compounds.

Pharmacological Evaluation of Alcoholic Extract of Clitoria ternatea Root for Anxiolytic and Anticonvulsant Activity

Recent scientifi c studies have indicated that some of the same medicinal herbs used in traditional medicine to treat epilepsy may also have anticonvulsant qualities, suggesting that they may be a possible source of novel anticonvulsants. Anticonvulsant properties have been studied in animal models. Clitoria ternatea Linn’s ethanolic root extract was examined for antiepileptic, anxiolytic, and phytochemical properties. Phenytoin 25 mg/kg, as a reference medicine, the extract was tested against strychnine-induced convulsion in rats at oral doses of 200 and 400 mg/kg. The elevated plus maze and staircase test were used to examine mice’s anxiolytic activity with lorazepam (the gold standard) at 0.05 mg/kg. When using a strychnine-induced convulsion model, the ethanolic extract markedly accelerated the start of convulsions. In the elevated plus maze test, Clitoria ternatea Linn ethanolic root extract at 200, 400, and standard doses signifi cantly increased the time and number of the entry in open arms compared to the control group. In a staircase test, the ethanolic root extract of Clitoria ternatea increased the number of steps climbed and lowered rearing compared to the control group. Docking scores in mcule software indicate that interactions with the glycine agonist (PDB: 5I57) and the GABA agonist (PDB: 4MS3) receptors for epilepsy and anxiety, respectively, are highly eff ective. Evidence for the biochemical evaluation of GABA, anticonvulsant, and anxiolytic action, as well as in-silico activities, of the ethanolic extract of Clitoria ternatea was reported in this work.

Antiepileptic Effect of Neuroaid® on Strychnine-Induced Convulsions in Mice.

NeuroAid II, a folk Chinese Medicine, is currently used in Asia for the treatment of stroke. An experimental study demonstrated that NeuroAid enables neuronal cells to be more resistant to glutamate toxicity. This research was constructed to evaluate the efficacy of NeuroAid in the prevention of epilepsy (EP). Forty healthy adult male mice were used and divided into four groups (10 mice/group): normal control group; positive control group; NeuroAid-treated group (10 mg/kg); topiramate-treated group (10 mg/kg). The treatment continued for 7 days, and on the last day, EP was induced using strychnine at a dose of 2 mg/kg via intraperitoneal (ip) administration. Seizure severity, latency to the seizure onset, the number of seizures, and the duration of each seizure episode were observed for one hour. The death and protection rates over the next twenty-four hours were recorded. Brain specimens from surviving animals were extracted and examined pathologically for quantification of glutamate receptor (GluR) gene expression in the isolated hippocampus employing real-time PCR analysis. Treatment with NeuroAid resulted in a significant reduction in seizure severity, prolonged the onset of seizures, decreased the number and duration of episodes, reduced brain insult, and decreased mortality rate. Reductions in the gene expression of GluRs in the hippocampus with minor histopathological changes were observed in the NeruoAid- and topiramate-treated groups. It is concluded that NeuroAid has a potential antiepileptic effect (EP) with the ability to prevent convulsion through its effect on the glutamate receptor.

Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract.

This study aimed to assess the potential of Lactuca serriola (Asteraceae) seed n-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where n-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially n-hexane extract (400 mg/kg)-which showed 456.14%-increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, L. serriola enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of L. serriola seeds.

Sedative and anticonvulsant activities of aqueous and ethanol dried leaf extracts of Solenostemon monostachyus in mice

This study evaluated the sedative, and anticonvulsant activities of the aqueous (AESM) and ethanol (EESM) dried leaf extracts of Solenostemon monostachyus. The sedative effect of the extracts was evaluated with ketamine-induced hypnosis (100 mg/kg, i.p.). Also, the anticonvulsant activity was evaluated using pentylenetetrazole (PTZ)-induced convulsion (85 mg/kg, i.p.), strychnine-induced convulsion (2 mg/kg, i.p.) and maximal electroshock (MES)-induced convulsion models. The AESM (200 mg/kg, p.o.) gave 66.67% protection, while EESM (800 mg/kg, p.o.) gave 100% protection against the hind limb tonic extension on the MES. The AESM only at 200 mg/kg, p.o. caused a significant change (p < 0.01) in the convulsion latency and time of death in PTZ –induced convulsion. The AESM and EESM (200, 400 and 800 mg/kg, p.o.) significantly (p < 0.05 – 0.01) shortened sleep latency. At 400 and 800 mg/kg, p.o., AESM prolonged (p < 0.05) total sleeping time while EESM at 800 mg/kg, p.o. significantly (p < 0.05) prolonged total sleeping time relative to vehicle. The study concluded that the aqueous leaf and ethanol dried leaf extracts of S. monostachyus possessed sedative and mild anticonvulsant activities.

Methanol leaf extract of Paullinia pinnata exerts sleep-enhancing and anticonvulsant effects via a mechanism involving the GABAergic pathway

PurposeLeaf extracts of Paullinia pinnata L. (Sapindaceae) are used in ethnomedicine for the treatment of central nervous system-related diseases such as insomnia and epilepsy. We determined the bioactive constituents, sleep-enhancing and anti-convulsant potentials, and possible mechanisms of action of P. pinnata methanol leaf extract (PPME). MethodsGas Chromatography-Mass spectrometry (GC-MS) was used to identify the bioactive compounds in PPME. Adult Swiss albino mice were used. Oral LD50 was estimated before administering PPME at oral doses of 100, 200, and 400 mg/kg to test for sleep-enhancing and anticonvulsant properties. To evaluate the possible mechanisms involved, mice were pretreated for five days with isoniazid (NIH) a GABA synthesis inhibitor before re-evaluation of sleep-enhancing property. The activities of glutamic acid decarboxylase (GAD), superoxide dismutase (SOD), catalase (CAT), and the level of malondialdehyde (MAD) in the brain of mice were also evaluated after a 7-day treatment with the extract. ResultsTwenty-five phytochemical compounds were identified from GC-MS analysis with fatty acid esters of lauric and fumaric acids being the most abundant. The oral LD50 of PPME was estimated to be greater than 5000 mg/kg. Doses of PPME significantly (p < 0.001) reduced sleep latency and increased the duration of sleep of phenobarbital-treated mice. Except for 100 mg/kg, the doses also significantly protected mice against maximum electroshock (p < 0.001) and pentylenetetrazole (p < 0.05) but not strychnine-induced convulsions. Pretreatment with isoniazid (INH) almost completely reversed the sleep-enhancing effects of PPME. The activities of GAD, SOD, and CAT, and level of MDA in brains of the mice were significantly (p < 0.001) increased by doses of PPME administered for five days. ConclusionThe extract possesses sleep-enhancing and anticonvulsant properties which depend on increased level of GABA in the brain. Its antioxidant action may be neuroprotective against free radicals-induced damage.

Ceiba pentandra (L.) Gaertn hydroethanolic leaf extract exhibits anticonvulsant properties in mouse models

BackgroundCeiba pentandra (L.) Gaertn. (Malvaceae) is a plant documented folklorically to be used in the management of epilepsy but with no scientific evidence to support its efficacy. AimThe aim of this study was to evaluate the anticonvulsant properties of a hydroethanolic leaf extract of Ceiba pentandra (CPLE). MethodsMouse models of acute seizures [maximal electroshock (MES)-, 4-aminopyridine (4-AP)-, pentylenetetrazole (PTZ)-, strychnine- and picrotoxin (PIC)- induced seizure tests)] and status epilepticus (lithium/pilocarpine test) were employed to investigate the anticonvulsant properties of CPLE (30–300 mg/kg, p.o.). The effects of CPLE on motor coordination (rotarod test) and spontaneous locomotor activity (open field test) were also examined. The study further investigated the possible involvement of GABAergic mechanisms in the actions of the extract. ResultsCPLE, given orally, delayed the onset and reduced the frequency and duration of PTZ- and PIC-induced convulsions. Additionally, CPLE delayed the onset of convulsions and prolonged survival in the 4-aminopyridine test. The extract also prolonged survival in the MES test. CPLE, however, failed to attenuate strychnine-induced convulsions. The extract reduced severity of convulsions and increased the latency to status epilepticus in the lithium-pilocarpine test. Pre-treatment of the animals with flumazenil (1 mg/kg, i.p.) reversed the anticonvulsant effect of the extract (100 mg/kg) against PTZ-induced convulsions. The extract (at 300 mg/kg) impaired motor coordination in the rotarod test and reduced locomotor activity in the open field arena. ConclusionThe present findings indicate that Ceiba pentandra leaf extract has significant anticonvulsant properties in mouse models. These observations justify the traditional use of Ceiba pentandra for the management of seizure conditions.

Anticonvulsant activity of methanolic extract of Withania cogulans in mice

Mental and neurological diseases including depression, Parkinson's disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world's disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity.

Toxicity Study and Anticonvulsant Effect of Ethanol Leaf Extract of Piliostigma thonningii Milne-Redhead (Fabaceae)

Background: Piliostigma thonningii (Schumach) Milne-Redhead [Fabaceae] is a plant widely used locally for the treatment and management of several ailments which include epilepsy in Northeastern Nigeria.Objectives: This study aimed at evaluation of the toxicity and anticonvulsant effect of ethanol leaf extract of Piliostigma thonningii in rats and mice with a view to determining the efficacy of the plant as an anticonvulsant drug.Methods: Fresh leaves of Piliostigma thonningii were air-dried, pulverized and extracted using soxhlet extraction apparatus. Acute toxicity study was carried out by Lorke’s method and the anticonvulsant activity of the ethanol leaf extract was carried using pentylenetetrazole and strychnine-induced convulsion model on Wistar strain albino rats and mice respectively.Result: The soxhlet extraction yielded 21.04% w/w of extract after being concentrated. The oral and intraperitoneal LD50 were ≥ 5000 mg/kg implying that the extract is relatively safe according to literatures. Anticonvulsant effect of the ethanol leaf extract using pentylenetetrazole (PTZ), revealed the ability of the extract to confer protection on rats treated with doses of 200, 400 and 600 mg/Kg bd. wt. by exerting 60%, 80% and 80% protection on rat against PTZ induced convulsion respectively in a dose dependent manner as well as protected 20%, 60% and 80% of mice against death induced by strychnine when treated with 100, 200 and 400 mg/kg of ethanol extract.Conclusion: The ethanol leaf extract of Piliostigma thonningii was able to provide anticonvulsant effect and is relatively safe for consumption as medicine.

The Anticonvulsant Effect of Hydroethanolic Leaf Extract of Calotropis procera (Ait) R. Br. (Apocynaceae).

A number of currently used drugs have been obtained from medicinal plants which are a major source of drugs. These drugs are either used in their pure form or modified to a semisynthetic drug. Drug discovery through natural product research has been fruitful over the years. Traditionally, Calotropis procera is used extensively in the management of epilepsy. This study is conducted to explore the anticonvulsant effect of a hydroethanolic leaf extract of Calotropis procera (CPE) in murine models. This effect was evaluated using picrotoxin-induced convulsions, strychnine-induced convulsions, and isoniazid- and pilocarpine-induced status epilepticus in mice of both sexes. The results showed that CPE (100-300 mg/kg) exhibited an anticonvulsant effect against strychnine-induced clonic seizures by significantly reducing the duration (p = 0.0068) and frequency (p = 0.0016) of convulsions. The extract (100-300 mg/kg) caused a profound dose-dependent delay in the onset of clonic convulsions induced by picrotoxin (p < 0.0001) and tonic convulsions (p < 0.0001) in mice. The duration of convulsions was reduced significantly also for both clonic and tonic (p < 0.0001) seizures as well. CPE (100-300 mg/kg), showed a profound anticonvulsant effect and reduced mortality in the pilocarpine-induced convulsions. ED50 (~0.1007) determined demonstrated that the extract was less potent than diazepam in reducing the duration and onset of convulsions but had comparable efficacies. Flumazenil—a GABAA receptor antagonist—did not reverse the onset or duration of convulsions produced by the extract in the picrotoxin-induced seizure model. In isoniazid-induced seizure, CPE (300 mg kg1, p.o.) significantly (p < 0.001) delayed the onset of seizure in mice and prolonged latency to death in animals. Overall, the hydroethanolic leaf extract of Calotropis procera possesses anticonvulsant properties.

Novel Protection by Omega-3-FAs against Strychnine-Induced Tonic-Convulsion in Mice: Synergy with Carbamazepine

Background/Aim: The utility of ω-3-FAs (DHA and EPA) against epilepsy was evident in clonic-convulsion animal-models, in their chronic- than acute-modes. However, their efficacy against tonic-convulsion-models remained unclear. Besides, while some-antiepileptics (AEDs), like carbamazepine (CBZ), adversely impacted the bioavailability of dietary ω-3-FAs, it remains unclear whether co-ω-3-FAs may change efficacy/blood-levels of CBZ. This work investigated the capacity of both acute- versus chronic-regimens of ω-3-FAs to: 1) alleviate the-tonic, strychnine-induced convulsions in mice, and 2) synergize with CBZ-evoked anti-tonic-convulsions, and then further-probe whether this has altered plasma-CBZ levels (clearance).

Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H2O2-Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways.

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole- (PTZ) and strychnine-induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ-induced mice. Furthermore, the H2O2-treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK-8 results showed that CPM significantly improved the cell viability of H2O2-treated PC12 cells. Results of the acridine orange- (AO-) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2-induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved- (C-) caspase-3, and C-caspase-9, and upregulated Bcl-2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in H2O2-induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) and increase the expression of heme oxygenase-1 (HO-1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.

Central nervous system evaluation of an ethanol extract of Bidens odorata Cav (Asteraceae) leaves, and its antinociceptive interaction with paracetamol and naproxen.

Bidens odorata Cav (Asteraceae) is a medicinal plant employed for the treatment of pain, anxiety, and depression. This study aimed to evaluate some neuropharmacological effects of an ethanol extract of B. odorata (BOE) and assess its antinociceptive interaction with naproxen and paracetamol. The following neuropharmacological effects were evaluated with the ethanolic extract of B. odorata leaves (BOE) (10-200mg/kg p.o.): the strychnine-induced-convulsion assay (anticonvulsant effect), rotarod test (locomotor activity), tail suspension test (anti-depressant-like activity), cylinder exploratory test (anxiolytic-like actions), and pentobarbital-induced sleep test (sedative effect). The interaction of the BOE-paracetamol and BOE-naproxen combinations were evaluated with the acetic acid-induced writhing test. The ED50 value of each drug was estimated and the combinations of paracetamol and naproxen with BOE were calculated. BOE (100-200mg/kg) showed anti-convulsant activity by increasing the latency to occurrence of strychnine-induced convulsions, antidepressant-like effects by 28% and 33%, respectively, exerted anxiolytic actions (ED50 = 125mg/kg), but did not affect motor locomotion. The pre-treatment with 2mg/kg flumazenil or 20mg/kg pentylenetetrazol partially reverted the anxiolytic activity shown by BOE alone. BOE (200mg/kg) prolonged the duration of sleep with similar effect in comparison to clonazepam (1.5mg/kg). The combinations of BOE-paracetamol (1:1) and BOE-naproxen (1:1) showed antinociceptive synergism. BOE induces sedative and anticonvulsant effects. The anxiolytic actions shown by BOE are probably induced by the participation of the GABAergic system. BOE exerts antinociceptive synergistic interaction with paracetamol and naproxen probably by the participation of nitric oxide and ATP-sensitive K+ channels, respectively.

Folklore poly herbal extract: How is it implicated in the control of seizure susceptibility?

Epilepsy is a chronic neurological disorder characterized by anenduring predisposition to generate seizures, may be associated with emotional and cognitive dysfunction. The study was to examine the antiepileptic potential of folklore polyherbal extract (PHE) which consists ofPterocarpus Santalinus, Mesua Ferrea. Linn. and Vetiveria zizanioides in experimental models of epilepsy using swiss albino mice. Ethanolic extract of three driedpowders taken from stamens of Mesua Ferrea. Linn. (MF), heart wood of Pterocarpus Santalinus (PS) and roots of Vetiveria zizanioides (VZ) were evaluated against Maximum Electroshock (MES) and Strychnine Induced Convulsions (SIC). The preliminary qualitative phytochemical analysis of PHE showed presence of alkaloids, flavonoids, steroids, saponins, triterpenoids and glycosides. The extract was subjected to behavioral parameters, anxiolytic, locomotor activity and motor co-ordination activity and also estimated biogenic amines in the brain. The PHE was showed anticonvulsant activity against MES-induced convulsion; tonic extension phase was abolished and offered a significant inhibition against SIC. PHE exhibited significantly increased the brain levels of serotonin, dopamine, noradrenaline and monoamine. PHE shows significant effect in behavioral activities at thedose of 500 mg/kg when compared to standard drug phenytoin (25mg/kg).The PHE contains flavones and saponins which may responsible for its CNS activity. The present study indicates the PHE possess the anti-epileptic activity by different mechanisms. Future studies are required to know the molecular mechanism of actions of PHE. Effect of Polyherbal extract on maximal electroshock induced seizures in miceTabled 1GroupsDuration of HLTE (sec)Quantal protection% protectionControl15.67±0.514/666.67Polyherbal extract14.33±0.81*5/683.33Phenytoin (25mg/kg)15.33±0.51*6/6100 Open table in a new tab

English

Insulin, an important regulator of peripheral metabolism, has been reported to interact with many neurotransmitter systems including those associated with convulsion. The effect of insulin against pentylenetetrazole and strychnine-induced convulsions in mice, as well as possible sex differences, were evaluated in this study. Mice of both sexes weighing between 20 and 25 g were administered insulin intraperitoneally at doses of 1, 2, 4 and 8 IU/kg. Each mouse received a convulsive dose of pentylenetetrazole (100 mg/kg, i.p.) or strychnine (2 mg/kg, i.p.) and was observed for the onset of convulsions and occurrence of death. Against pentylenetetrazole-induced convulsions, all the doses of insulin used significantly (p < 0.05) prolonged the onset of convulsions and significantly delayed the time of death in male mice when compared with control. However, in female mice, only insulin 8 IU/kg significantly prolonged the onset of convulsions, while insulin 4 IU/kg significantly delayed the time of death. Against strychnine-induced convulsions, insulin at the doses of 2 and 4 IU/kg significantly (p < 0.05) prolonged the onset of convulsions in male mice relative to control, while 8 IU/kg insulin significantly prolonged the time of death in male mice compared to control. However, none of the doses of insulin administered to female mice were effective against strychnine-induced convulsions. These results show that insulin produced sex-related protective effects against chemically-induced convulsions in mice. Keywords: Insulin, convulsion, pentylenetetrazole, strychnine, male mice, female mice.

Anxiolytic Action of Taurine via Intranasal Administration in Mice.

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

Evaluation of some neuropharmacological effects of Caladium bicolor aiton (araceae) leaf extracts in mice.

Caladium bicolor Aiton (Araceae) is used in ethnomedicine for the treatment of boils, wound ulcers and convulsion. This study investigated the effects of the leaf extracts on some neuropharmacological parameters. The leaves were collected, dried, powdered and then extracted by maceration in methanol to yield the whole extract (WE). Extraction was also done using n-hexane, ethyl acetate and methanol in a Soxhlet apparatus to obtain n-hexane (HE), ethyl acetate (EA) and methanol (ME) extracts. Preliminary phytochemical screening was done using the whole extract. Some neuropharmacological evaluations were carried out using standard methods. Phytochemical screening revealed the presence of carbohydrates, proteins, alkaloids and flavonoids. WE showed varying levels of protection against strychnine-induced convulsion. Each of HE, EA and ME increased latency (P < 0.01) to pentylenetetrazole-induced convulsion and offered varying levels of protection against maximal electroshock-induced seizure. Each of WE, HE and ME significantly increased the duration of stay on the open arm of the elevated plus maze. Both EA and ME at doses of 100 and 200mg/kg, and HE at a dose of 400mg/kg significantly reduced the duration of immobility in forced swim test. It is concluded that the leaf extracts possess anticonvulsant, anxiolytic and antidepressant properties.

Anticonvulsant, Muscle Relaxant and In-vitro Antioxidant Activities of Hydroethanol Leaf Extract of Newbouldia laevis Seem. (Bignoniaceae) in Mice

Background: Newbouldia laevis Seem. (Bignoniaceae) is a woody tropical plant employed by traditional medicine practitioners (TMPs) in Nigeria in the treatment of various disease conditions, including central nervous system disorders. Objective: To evaluate the anticonvulsant, sedative-hypnotic, muscle relaxant and in-vitro antioxidant activities of the hydroethanol leaf extract of Newbouldia laevis (HNL). Materials and Methods: HNL (25–200 mg/kg, p.o.), distilled water (10 ml/kg, p.o.) or diazepam (3 mg/kg, p.o.) were administered 1 h before strychnine or picrotoxin-induced seizure, thiopentone-induced hypnotic, inclined plane and traction tests in mice. The in-vitro antioxidant activity of HNL was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide, hydrogen-peroxide scavenging, lipid peroxidation and reducing power assays. The total antioxidant capacity, total phenolics and total flavonoids were also determined. Results: In the picrotoxin-induced convulsion test, HNL (100 mg/kg) increased the latency (p&lt;0.05) and decreased the duration (p&lt;0.001) of seizure. The extract was not effective in the strychnine-induced convulsion test. The extract at 100 and 200 mg/kg signigicantly increased the latency (p&lt;0.001, 0.05 respectively) but not duration of sleep in the thiopentone-induced hypnosis test. In the inclined screen model, the extract at 100 mg/kg significantly reduced the post-treatment sliding latency (p&lt;0.05) compared to the pre-treatment value. The total antioxidant capacity, total phenolics and total flavonoids were 42.65±0.16, 44.49±0.15 and 23.61±0.18 mg/100 g of standards equivalent respectively. HNL in a concentration-dependent manner scavenged reactive species in the in-vitro antioxidant tests. Conclusion: The findings in this study showed that HNL possesses anticonvulsant, muscle relaxant and antioxidant activities. This confirms the beneficial property of the extract in the treatment of seizures.

Quercetin Exerts Anti-convulsant Effects in Animal Model of Grand Mal Epilepsy: Modulation of GABA and Glycinergic Pathways

Quercetin is low molecular weight flavonoid having multiple neuropharmacological actions. Recently, its anticonvulsant effect was reported in rats using electrical kindling models. However, earlier cell culture studies have documented antagonistic action of quercetin on GABAA, GABAC and Glycine channels, which is contrary to recent findings. Hence, the present study aimed at characterizing the effects of quercetin administration in various experimental models of epilepsy. Dose-dependent effects of quercetin on maximal-electroshock seizure (MES) were determined. Further, the effective dose was tested in pentylenetetrazol-induced seizures (PTZ), and strychnine-induced seizures to study the involvement of GABA and Glycinergic receptors. The results revealed a potent anticonvulsant effect of quercetin in MES induced seizures at a dose of 5 and 10 mg/kg. This effect was found to be retained in case of PTZ-induced convulsions and strychnine-induced convulsions (quercetin 10 mg/kg). The present finding warrants further substantiation along with their correlation to molecular mechanism of action.

Evaluation of anticonvulsant potential of aqueous methanolic extract and various fractions of Ajuga bracteosa wall

We aim to assess the anticonvulsant potential of Ajuga bracteosa Wall. The aqueous methanol extract (30:70) of Ajuga bracteosa and its n-hexane, chloroform and ethyl acetate fractions were prepared. Anticonvulsant effect was evaluated using different animal models of epilepsy. Crude extract along with its fractions at 500 and 1000 mg/kg doses, administered orally to albino mice were appraised against pentylenetetrazole-induced, strychnine-induced and picrotoxin-induced convulsions. Moreover, effect of test substances on brain GABA level and phenobarbitone induced hypnosis was also studied at dose level of 350 and 400 mg/kg. The plant extract and its fractions produced potent dose dependent anticonvulsant activity in all models of epilepsy. In addition, plant extract and fractions increased brain GABA level and potentiated phenobarbitone-induced sleep duration. From the results it can be deduced that Ajuga bracteosa possess potent anticonvulsant activity, supporting its folkloric use in the treatment of epilepsy.