Pentylenetetrazole Induced Seizure Test Research Articles

ANTICONVULSANT EFFECT OF ISOLATED COMPOUNDS FROM THE LEAVES OF GLOBIMETULA BRAUNII ENGLER VAN TIEGH (LORANTHACEAE) IN MICE AND CHICKS

The anticonvulsant evaluation of globrauneine A (1), globrauneine C (2) globrauneine D (3), globrauneine F (4), lupeol (5), β-sitosterol (6), (1R,5S,7S)-7-[2-(4-hydroxyphenyl) ethyl]-2,6-dioxabi-cyclo [3. 3.1]-nonan-3-one (7), dodoneine (8), quercetin (9) and rutin (10) from Globimetula braunii leaves were analyzed with the aid of pentylenetetrazole-induced seizure test in mice (PTZ) and maximal electroshock seizure test in chicks (MEST), while the neurotoxicity was evaluated using the beam walking assay in mice. 50% of the tested mice were protected by Globrauneine A (1) and dodoneine (8) against PTZ-induced mortality. The mean onset of clonic spasm of the unprotected animals was increased by Quercetin (9) and also the mice were differentially protected against mortality. The tested compounds also produced significant (p<0.05) increase in the mean onset of seizure against pentylenetetrazole-induced seizure. The chicks were not protected by the tested compounds against MEST and the recovery time was not significantly reduced. In the beam assay, with the exception of dodoneine (8), the number of foot slips and the time taken to complete the task was not significantly changed by the tested isolated compounds, suggesting that the observed activities are not due to general CNS depression. The results suggest mild protective effects of these isolated compounds against seizure which might be useful in the control of petit mal epilepsy.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14-16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12-20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Neuropharmacological Activity of the Acetonic Extract of Malpighia mexicana A. Juss. and Its Phytochemical Profile

Mental and neurological disorders are conditions that affect thoughts, emotions, behavior, and relationships. Malpighia mexicana A. Juss. is a plant used in Mexican traditional medicine for the treatment of such disorders. This work aimed to investigate the antidepressant, anxiolytic, sedative, hypnotic, and anticonvulsant effects of the acetonic extract (MmAE) of M. mexicana and its fractions (F3, F4-10, F14) using the forced swimming test (FST), elevated plus maze (EPM), open field test (OFT), pentobarbital-induced sleep test (PBTt), and pentylenetetrazol-induced seizure test (PTZt). MmAE, F3, F4-10, F14, and vehicle were administrated orally 24, 18, and 1 h prior to the evaluations. Imipramine (15 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the FST, while diazepam (1 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the EPM, OFT, PBTt, and PTZt. MmAE had an anxiolytic effect; MmAE and F3, F4-10, and F14 showed an antidepressant effect, sedative effect, hypnotic effect, and anticonvulsant effect. Using HPLC, we identified the compounds quercetin 3-O-rutinoside (1), kaempferol 3-O-glucoside (2), luteolin 7-O-glucoside (3), quercetin (4), and kaempferol (5) in MmAE and compounds (1), (2), and (3) in F14. Using GC-MS, we identified α-tocopherol, phytol, and β-amyrin in F3; β-tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10; and α- tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10. The neuropharmacological effects found in this work may be due to the presence of vitamins, phytosterols, terpenes, and flavonoids. This research requires further study to clarify the mechanisms of action of the identified compounds.

In Vivo Neuropharmacological Effects of Neophytadiene.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Central depressant effects of Piper tuberculatum Jacq essential oil in mice

This study aims to investigate the toxicity and possible effects and mechanism of action of the essential oil obtained from the Piper tuberculatum Jacq.‘s fruit (EOPT) on the central nervous system (CNS) of mice. In the Hippocratic test, it was observed ambulation reduction, sedation, piloerection and mortality of 25% at the dose of 1000 mg/kg and 50% at the dose of 5000 mg/kg. The results found demonstrate that the EOPT is endowed with a possible depressant effect, and is characterized by a likely sedative (open field test), anxiolytic-like (elevated plus maze test), anticonvulsant (pentylenetetrazole-induced seizure test) and hypnotic action (pentobarbital-induced sleeping time). These effects may possibly occur due to the interaction between the monoterpenes, present in its essential oil, and the GABAergic pathway confirmed by reversion of the effects by flumazenil. Then, these results demonstrate the therapeutic potential and the validation of the ethnopharmacological use of this species in the treatment of disorders affecting the central nervous system.

EVALUATION OF PHARMACOLOGICAL EFFECT OF CASSIA SOPHERA LINN LEAVES EXTRACTS

Instroduction: Cassia sophera Linn (C. sophera) is a medicinally important plant belonging to the family of Caesalpiniaceae. The whole part of the plant is used as traditional folk medicine and is reported to possess analgesic, anticonvulsant, antioxidant, anti-inflammatory, hepatoprotective and antiasthmatic activity.
 Materials and Methods: Eddy’s hot plate and Analgesiometer tests were used to asses the antinociceptive activity of Cassia sophera. Pentobarbitone narcosis potentiation test was used to evaluate the hypnotic and sedative effect, while anticonvulsant activity was evaluated by Maximum electroshock-induced seizure test and Pentylenetetrazol induced seizure test.
 Results and Discussion: Test drug (440 mg/kg) produced significant analgesia, potentiated the pentobarbitone induced sleeping time and exhibited anticonvulsant effect against hind limb tonic extension phase of maximum electroshock-induced seizure test and seizures induced by pentylenetetrazol.
 Conclusion: The preliminary screening of seed extract of Cassia sophera, Linn. exhibited analgesic, anticonvulsant effects and potentiated pentobarbitone sleeping time. The ethanol extract of seed of Cassia sophera, Linn. deserves further investigation to elucidate the mechanisms of action.

Effect of aliskiren on the anticonvulsant activity of antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice

Drug-drug interactions should be considered during the pharmacological treatment in patients with epilepsy and coexisting hypertension. Experimental studies in rodents showed that antihypertensive drugs which block the renin-angiotensin system (RAS) are able to decrease seizure severity. The anticonvulsant efficacy of several antiepileptic drugs (AEDs) was enhanced in different seizure models following concomitant treatment with RAS inhibitors. The current study examined the combined treatment with AEDs (carbamazepine, valproate, phenobarbital, clonazepam, ethosuximide, levetiracetam) and aliskiren, the first inhibitor of renin for treating hypertension, in the mouse 6 Hz psychomotor seizure model. The convulsive threshold was not affected by the renin inhibitor up to a dose of 75 mg/kg i.p. However, aliskiren (75 mg/kg) enhanced the anticonvulsant action of valproate reducing its ED50 value from 96.7 to 25.6 mg/kg (P < 0.01). The anticonvulsant potency of other AEDs was unaffected by aliskiren treatment. The combinations of aliskiren with AEDs did not cause adverse effects in mice evaluated in the rota-rod or passive avoidance task. Administration of the renin inhibitor did not significantly alter either plasma or brain concentration of valproate. The obtained results confirm earlier findings from other seizure tests (maximal electroshock and pentylenetetrazole-induced seizure test) that aliskiren has a neutral or positive effect on the anticonvulsant efficacy of AEDs, which suggest its safe use for the treatment of high blood pressure in patients with epilepsy. The beneficial anticonvulsant effect of the concomitant treatment with aliskiren and valproate is worthy of recommendation to further both preclinical and clinical studies.

Anticonvulsant studies on the isolated compounds from the leaves of Scurrula parasitica L (Loranthaceae)

The leaves of Scurrula parasitica were effectively extracted by means of cold extraction method. Fractionation and purification of the n -hexane, ethyl acetate and methanol crude extracts yielded eight compounds. The compounds were identified as quercetin 1 , quercitrin 2 , kaempferol 3- O -a-L-rhamnoside 3 , (+)-catechin 4 , lupeol 5 , lupeol palmitate 6 , b-sitosterol 7 and squalene 8 . Compounds 1 , 4 , 5 and 6 were investigated for anticonvulsant potentials using maximal electroshock test in chicks and pentylenetetrazole-induced seizure test in mice while the effect of the compounds on motor coordination was investigated using beam walking assay in mice. The compounds did not completely protect the mice against pentylenetetrazole-induced seizure, but increased the mean onset of myoclonic jerks and spasms in the animals. Quercetin significantly ( p < 0.05) increased the mean onset of spasm in the unprotected animals. The compounds also differentially protected the mice against mortality. Conversely, the compounds did not protect the chick against the MEST. Similarly, they did not significantly reduce the recovery time. In the beam walking assay, the increase in the number of foot slips observed in the study may be associated with the interaction of quercetin and (+)-catechin with the GABA system to produce clinical sedation. The findings of the present study suggest that the isolated compounds possess some mild anticonvulsant potential and may be beneficial in the management of petit mal epilepsy.

Neuropharmacological effects of d-pinitol and its possible mechanisms of action.

The aim was to evaluate the diuretic and neuropharmacological actions of d-pinitol and describe a possible mechanism of action. The diuretic effects of d-pinitol were evaluated using mice placed in metabolic cages. The sedative, anxiolytic-like, antidepressant-like, and anticonvulsant effects of 1-100mg/kg d-pinitol were assessed. The possible mechanisms of action of the anxiolytic-like, antidepressant-like, and anticonvulsant effects of d-pinitol were evaluated using inhibitors. d-pinitol lacked diuretic effects. However, d-pinitol showed the highest anxiolytic-like actions (ED50 =70mg/kg p.o. in mice) in the cylinder exploratory test and the highest antidepressant-like activity in the forced swimming test (ED50 =26mg/kg p.o. in mice). d-pinitol (100mg/kg) exerted anticonvulsant actions in the pentylenetetrazole-induced seizures test. The pre-treatment with 2mg/kg flumazenil reverted the anxiolytic-like actions and the anticonvulsant effects of d-pinitol, whereas the pre-treatment with 1mg/kg yohimbine and 0.05mg/kg prazosin abolished the antidepressant effects of d-pinitol. PRACTICAL APPLICATIONS: d-pinitol (3-O-methyl-d-chiro-inositol) is a polyol found in many fruits, as well as in many members of the Leguminosae and Fabaceae families. The results propose that this compound could contribute in the treatment of anxiety, depression, and convulsions. The findings suggest the possible participation of the GABAergic system in the anxiolytic-like and anticonvulsant actions of d-pinitol, whereas the noradrenergic system is probably involved in the antidepressant effects of d-pinitol. This study provides new information about other pharmacological uses for d-pinitol.

Phytochemical, antibacterial and anticonvulsant activity of the stem bark of &lt;i&gt;Lannea kerstingii&lt;/i&gt; Engl. &amp; K. Krause (Anacadiaceae)

The stem bark of Lannea kerstingii Engl. & K. Krause was investigated for its phytochemistry, acute toxicity, antibacterial and anticonvulsant activit ies. Standard methods were used to evaluate phytochemistry while antibacterial activity was determined using agar diffusion and broth dilution method s on Staphylococcus aureus , Salmonella typhii , Pseudomonas aeruginosa , Klebsiella pneumonia , Proteus vulgaris , Escherichia coli and Bacillus subtilis . Maximal electroshock-induced seizures test in chicks and pentylenetetrazole-induced seizures test in mice were used to determine the anticonvulsant activity. Phytochemical studies revealed the presence of flavonoids, tannins, carbohydrates steroids and triterpenes. Ethyl acetate and methanol fractions of the stem bark were found to be active against S. aureus , S. typhi , P. aeruginosa , K. pneumoniae , Proteus sp, E. coli , Bacillus subtilis with zone of inhibition ranging from 20-27.5mm and MIC ranging from 6.25mg/mL to 100mg/mL and MBC from 50mg/mL and above. LD 50 was found to be 2154.066 mg/kg. The crude methanol extract of the stem bark afforded dose (150, 300 and 600mg/kg) dependent protection to the laboratory animals against the hind limb tonic extension though not statistically significant (P<0.05) showing the inability of the extract to inhibit seizure discharge within the brainstem seizure substrate. Meanwhile the extract at doses of 300 and 600mg/kg significantly (P<0.05) prolonged the onset of seizure in pentylenetetrazole (PTZ) test showing the potential of this plant in raising seizure threshold in the brain therefore making it beneficial in the treatment of myoclonic and absence seizures. This justifies the use of the plant in treating convulsion. Keywords: Lannea kerstingii ; Anticonvulsant; Phytochemical; Antibacterial; Phytochemistry

ONO-8590580, a Novel GABAAα5 Negative Allosteric Modulator Enhances Long-Term Potentiation and Improves Cognitive Deficits in Preclinical Models.

GABAA receptors containing α5 subunits (GABAAα5) are highly expressed in the hippocampus and negatively involved in memory processing, as shown by the fact that GABAAα5-deficient mice show higher hippocampus-dependent performance than wild-type mice. Accordingly, small-molecule GABAAα5 negative allosteric modulators (NAMs) are known to enhance spatial learning and memory in rodents. Here we introduce a new, orally available GABAAα5 NAM that improves hippocampal functions. ONO-8590580 [1-(cyclopropylmethyl)-5-fluoro-4-methyl-N-[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine] binds to the benzodiazepine binding sites on recombinant human α5-containing GABAA receptors with a Ki of 7.9 nM, and showed functionally selective GABAAα5 NAM activity for GABA-induced Cl- channel activity with a maximum 44.4% inhibition and an EC50 of 1.1 nM. In rat hippocampal slices, tetanus-induced long-term potentiation of CA1 synapse response was significantly augmented in the presence of 300 nM ONO-8590580. Orally administered ONO-8590580 (1-20 mg/kg) dose-dependently occupied hippocampal GABAAα5 in a range of 40%-90% at 1 hour after intake. In the rat passive avoidance test, ONO-8590580 (3-20 mg/kg, by mouth) significantly prevented (+)-MK-801 hydrogen maleate (MK-801)-induced memory deficit. In addition, ONO-8590580 (20 mg/kg, p.o.) was also effective in improving the cognitive deficit induced by scopolamine and MK-801 in the rat eight-arm radial maze test with equal or greater activity than 0.5 mg/kg donepezil. No anxiogenic-like or proconvulsant effect was associated with ONO-8590580 at 20 mg/kg p.o. in the elevated plus maze test or pentylenetetrazole-induced seizure test, respectively. In sum, ONO-8590580 is a novel GABAAα5 NAM that enhances hippocampal memory function without an anxiogenic or proconvulsant risk.

Anticonvulsant activity of Nigella sativa, Aegle marmelos and Benincasa hispida in Pentylenetetrazole induced seizure in Swiss albino mice

Aims and Objectives: To test anticonvulsant properties of three medicinal plants with pentylenetetrazole induced seizure test in Swiss albino mice.Materials and Methods: Herbs selected for the work (leaves of Aegle marmelos, seed of Nigella sativa, and fruit of Benincasa hispida) were collected locally from Mangalore, India and were authenticated by a Taxonomist. Aqueous extract of Aegle marmelos leaves (AmAE) and Ethanolic extract of Nigella sativa seeds (NsEE) were prepared by Soxhlet extraction and separated from solvent using a water bath. Benincasa hispidafruit juice (BhE) was filtered and dried on a water bath. Qualitative phytochemical analysis of the test extracts were done with Preliminary chemical reaction tests, and Liquid chromatography–mass spectrometry (LC/MS). Male Swiss albino mice, 3-4 months of age, weighing 25-30g were used in the study. Extracts and vehicle were administered orally 1 hour prior to inducing convulsions. Test employed for screening anticonvulsant properties was Pentylenetetrazole (PTZ) induced seizure test [60mg/kg/i.p]. Animals were treated with extracts at a dose of 900mg/kg orally. The results were compared with control group and test for analysis of variance and significance were done (ANOVA, Dunnett’s test).Results: Aqueousextract of Aeglemarmelos leaves and Ethanolic extract of Nigella sativa seeds possess anticonvulsant property in Pentylenetetrazole (PTZ) induced seizure model, Crude extract of Benincasahispida fruits did not show statistically signifi cant anticonvulsant property.Conclusions: Aeglemarmelos leaf and Nigella sativa seed possess anticonvulsant propertiesin pentylenetetrazole induced seizures, this is in accordance with many other publishedreports on the same herbs with different animal models and indicates effectiveness inhuman absence seizure patients.Asian Journal of Medical Sciences Vol. 7(3) 2016 97-102

Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones

Synthesis of chalcones (1,3-diarylprop-2-en-1-ones) and 2-pyrazoline derivatives has been an active field of research due to their established pharmacological effects. In this study, a series of chalcones were prepared with methyl aryl ketones and substituted aldehydes in the presence of sodium hydroxide and methanol through Claisen-Schmidt condensation. 3,5-Disubstituted-4,5-dihydro-1H-pyrazole-1-carbothioamides were synthesized by refluxing selected chalcones and thiosemicarbazide in alkaline medium. Similarly N-3,5-trisubstituted-4,5-dihydro-1H-pyrazole-1-carboxamides were synthesized by refluxing selected chalcones with N-(4-chlorophenyl)semicarbazide in alkaline medium. Structures of the synthesized compounds were confirmed by elemental analysis and spectral (UV, IR, 1H NMR, 13C NMR, and mass) data, which were in line with the proposed structures.All compounds were tested for their anticonvulsant activity using pentylenetetrazole induced seizure (PTZ) and maximal electroshock seizure (MES) tests in mice at a dose level of 50mg/kg. Among the 2-pyrazoline-1-carbothioamide derivatives, 5-(2,6-dichlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2e) reduced grade-5 seizure activity and also increased survival rate in PTZ test. In MES test, 5-(4-methoxyphenyl)-3-[4-(methylsulphonyl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide(2g) has not only decreased seizure severity, but also increased survival rate. Among the 2-pyrazoline-1-carboxamide derivatives, 3-(5-bromothiophen-2-yl)-N-(4-chlorophenyl)-5-(2,6-dichlorophenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide (3d) having 5-bromothiophen and 2,6-dichlorophenyl moieties and N-(4-chlorophenyl)-5-(2,6-dichlorophenyl)-3-(5-chlorothiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide (3e) having 5-chlorothiophen and 2,6-dichlorophenyl moieties showed remarkable activities in PTZ test. Among all tested derivatives, compound 3d was found to be the most active one and reduced grade-5 seizure severity and also increased survival rate.

Nebivolol enhances the anticonvulsant effect of gabapentin against various animal models of epilepsy in mice

In the present study the effect of acute administration of nebivolol (NBV) on increasing current electroshock (ICES) test, PTZ (pentylenetetrazole) induced seizures, spatial working memory and locomotor activity on rotarod in mice alone as well as in combination with gabapentin (GBP) were evaluated. The anticonvulsant effects of the drugs were measured using ICES and PTZ model whereas cognitive behavior was measured by the spontaneous alternation behavior and rotarod test. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH). Significant increased seizure threshold in ICES test and latency to clonic jerks in PTZ induced seizures test was found by NBV alone as well in combination with GBP. There was no effect on spatial working memory and locomotor activity. In addition NBV in combination with GBP significantly decreased the level of the lipid peroxidation and increased the level of GSH in brain. The Study showed that NBV potentiates the anticonvulsive activity of GBP, which can be useful for the treatment of epilepsy in patients with hypertension.

Neuropharmacological in vivo effects and phytochemical profile of the extract from the aerial parts of Heteropterys brachiata (L.) DC. (Malpighiaceae)

Ethnopharmacological relevanceHeteropterys brachiata is a plant species that has been used in traditional Mexican medicine for the treatment of nervous disorders. Aim of the studyTo evaluate the anxiolytic, anticonvulsant, antidepressant and sedative effects produced by the methanolic extract of Heteropterys brachiata (HbMeOH) in ICR mice. Additionally, we determine the acute toxicity profiles of the extract and the presence of its main constituents. Material and methodsThe neuropharmacological effects of the extract were evaluated using a variety of models, such as the elevated plus maze (EPM), the forced swimming test (FST), the pentobarbital potentiation test (PTBt), pentylenetetrazole-induced seizures test (PTZt), and the open field test (OFT). HPLC was employed for obtention of phytochemical profile. ResultsHbMeOH produced a significant antidepressant effect in FST at 500 and 750mg/kg doses, while doses from 500 to 1500mg/kg exhibited a clear dose-dependent anxiolytic activity in EPM. A dose of 500mg/kg showed a significant anticonvulsant activity in PTZt and an absence of sedation effects in PTBt. The main compounds of HbMeOH were chlorogenic acid and chlorogenic acid methyl ester, as well as less abundant terpene-type compounds. Furthermore, the extract was either safe with no deaths in mice treated orally with 2000mg/kg. ConclusionsHbMeOH extract which contains mainly hydroxycinnamic acids and triterpene-type compounds, possesses antidepressant, anxiolytic and anticonvulsive properties and can be considered safe or of low toxicity when orally administrated. These findings lend pharmacological justification to the traditional use of Heteropterys brachiata in the treatment of nervous disorders.

Synthesis and anticonvulsant activity of 6,7,8,9-tetra hydro-5H-5-(2′-hydroxy phenyl)-2-(4′-substituted benzylidine)-3-(4-nitrophenyl amino) thiazolo quinazoline derivatives

In this study, a series of thiazolo quinazoline derivatives were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal administration to mice by maximal electroshock- and subcutaneous pentylenetetrazole-induced seizure tests and minimal motor impairment was determined by rotorod test. A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. The most active compounds carry fluoro, bromo, or chloro substituents in the 4-position of the phenyl ring. The chemical structures of the synthesized compounds were confirmed by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Among the synthesized compounds, 6,7,8,9-tetra hydro-5H-5-(2′-hydroxy phenyl)-2-(4′-fluoro benzylidine)-3-(4-nitrophenyl amino) thiazolo quinazoline (5d) was found to be the most potent anticonvulsant activity.

Mildronate exerts acute anticonvulsant and antihypnotic effects

The effects of mildronate [3-(2,2,2-trimethylhydrazinium) propionate], an inhibitor of L-carnitine biosynthesis and an anti-ischaemic drug, were examined in various in-vivo conditions to investigate the neuropharmacological profile after acute administration. Mildronate (200 mg/kg, acute intraperitoneal administration) exerted anticonvulsant activity in a chemoconvulsant pentylenetetrazole-induced clonic and tonic seizure test but did not change the effects of a convulsion-inducing dose of (+)-bicuculline, a gamma-aminobutyric acid receptor antagonist. Mildronate also dose-dependently inhibited the sleeping time in ethanol-induced loss of righting reflex test. However, in a pentylenetetrazole-induced seizure test, mildronate significantly stimulated the anticonvulsant activity of ethanol. The anticonvulsant activity of mildronate was completely blocked after pre-treatment with alpha2-adrenergic receptor antagonist yohimbine (2 mg/kg) and nitric oxide synthase inhibitor N(G)-nitro-L-arginine (10 mg/kg). These results show that the acute administration of mildronate induces anticonvulsant and antihypnotic effects, which involve alpha2-adrenergic receptor and nitric oxide -dependent mechanisms. These findings indicate that the acute administration of mildronate could be beneficial for the treatment of seizures and alcohol intoxication.

Anxiogenic and proconvulsant effect of gatifloxacin in mice

The present study was performed to assess the neurological and neurobehavioural effects of gatifloxacin after its oral administration in two doses: 25 and 50 mg/kg for 7 days and 14 days in mice. The neurobehavioural parameters used for the short-term study (× 7 days) were pentylenetetrazole-induced seizure, forced swim test, elevated plus-maze, spontaneous alternation behaviour and rota-rod tests. However, only pentylenetetrazole-induced seizure and rota-rod tests were performed in long term (× 14 days) study. The results showed proconvulsant effect of gatifloxacin (50 mg/kg) in pentylenetetrazole-induced seizure test after both short- and long-term administration studies. Gatifloxacin in both doses showed an anxiogenic effect. However, in both doses, it did not show any effect on memory and mood as the drug did not show any effect in alternation behaviour and forced swim tests. In the long term study, gatifloxacin in 50 mg/kg, p.o. produced grip impairing effect only after 14 days of administration. These results reveal that gatifloxacin possesses proconvulsant and anxiogenic effects but it does not have an effect on mood and memory. Besides, long term administration of gatifloxacin for 14 days was found to reduce grip strength indicating its movement impairing effect in mice.

Synthesis and anticonvulsant activities ofN-Cbz-α-aminoglutarimidooxy carboxylate derivatives

Previous studies on the anticonvulsant activity of N-Cbz-alpha-aminoglutarimides have shown that the derivatives of N-Cbz-alpha-amino-N-alkoxy glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of N-Cbz-alpha-amino-glutarimidooxy carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of N-Cbz-alpha-amino-glutarimidooxy acetic acid 3a (ED50 = 42.9 mg/kg).

Synthesis and biological evaluation of new N-substituted- N′-(3,5-di/1,3,5-trimethylpyrazole-4-yl)thiourea/urea derivatives

Several thiourea and urea derivatives were prepared by the reaction of 4-aminopyrazoles with substituted isothiocyanates or isocyanates. The novel compounds were tested anticonvulsant activity using by pentylenetetrazole-induced seizure (PTZ) and maximal electroshock seizure (MES) tests. Among the tested compounds, thiourea derivatives of 4b were afforded 90 and 100% protection in PTZ and MES tests at 50 mg/kg, respectively. Urea derivatives of 5a and 5b were afforded 82 and 100% protection both at 25 and 50 mg/kg. Also synthesized compounds were screened for antituberculosis activity against Mycobacterium tuberculosis H 37Rv at 6.25 μg/mL concentration but they were not found active at these concentration. In addition, some selected compounds were evaluated for in vitro anti-HIV activity and they were all negative.