Anticonvulsant Activity Research Articles

Study of the anticonvulsant activity of the original valproic acid amino ester in various models of convulsive syndrome

Introduction. Despite a significant number of antidotes (atropine, pyridoxine) and anti-seizure drugs in clinical practice (benzodiazepines, barbiturates, valproates, anesthetics), the development of new antidotes for the relief of refractory seizures and recurrence of convulsive syndrome is actual problem. 
 The aim of the work was to study the specific pharmacological activity of a new original derivative of valproic acid in an experiment on models of convulsive syndrome with different mechanisms of action.
 Material and methods. A comparative study of the effectiveness of the original substance ((1-methylpiperidin-4-yl)-2-propylpentanoate hydrochloride, VAA) was carried out on electroshock, GABA-lytic, catecholamine-dependent seizure models in rats and mice.
 Results. A significant decrease in seizure activity was revealed in the group with prophylactic administration 
 of VAA in the dose range of 11, 27 and 65 mg/kg in comparison with the control group received only phenylcarbamate. In an intergroup comparison, a low dose (11 mg/kg) more than others had an effect on the latent period of the onset of phenylcarbamate seizures, an average dose (27 mg/kg) reduced the duration of the seizure period, a high dose (65 mg/kg) affected the severity of convulsions, while the integral indicator (convulsive activity) did not differ between the medium and high dose subgroups. There was no significant decrease in seizure activity in models with the use of corazol, camphor, and the model of maximum electric shock.
 Limitations. Testing of new pharmaceutical substances (study of efficacy and safety) should be carried out on laboratory animals before confirmation of efficacy in humans. The quantity of animals was limited by the need to comply with bioethical principles and sufficient number for statistically significant results and amounted 
 6 individuals in each group.
 Conclusion. The release of valproic acid during the metabolism of VAA is slow and its concentration is insufficient to realize the universal anticonvulsant activity of VAA. It is necessary to further study the effect on cognitive functions and neuroprotective properties. Since antidote efficacy superior to atropine has been previously demonstrated, VAA is recommended for development as an antidote for organophosphorus poisoning.

Additive Anticonvulsant Profile and Molecular Docking Analysis of 5,5'-Diphenylhydantoin Schiff Bases and Phenytoin.

Four 5,5'-diphenylhydantoin Schiff bases possessing different aromatic species (SB1-SB4) were recently synthesized and characterized using spectroscopic and electrochemical tools. The present study aimed to ascertain the anticonvulsant activity of the novel phenytoin derivatives SB1-Ph, SB2-Ph, SB3-Ph, and SB4-Ph, containing different electron-donor and electron-acceptor groups, and their possible mechanism of action. The SB2-Ph exhibited the highest potency to suppress the seizure spread with ED50 = 8.29 mg/kg, comparable to phenytoin (ED50 = 5.96 mg/kg). While SB2-Ph did not produce neurotoxicity and sedation, it decreased locomotion and stereotypy compared to control. When administered in combination, the four Schiff bases decreased the phenytoin ED50 by more than 2× and raised the protective index by more than 7× (phenytoin+SB2-Ph). The strongest correlation between in-vivo and docking study results was found for ligands' interaction energies with kappa and delta receptors. These data, combined with the worst interaction energies of our ligands with the mu receptor, suggest that the primary mechanism of their action involves the kappa and delta receptors, where the selectivity to the kappa receptor leads to higher biological effects. Our findings suggest that the four Schiff bases might be promising candidates with potential applications as a safe and effective adjuvant in epilepsy.

Mechanochemical synthesis and anticonvulsant activity of 3-aminopyrrolidine-2,5-dione derivatives

A series of 3-aminopyrrolidine-2,5-dione derivatives was synthesized and tested for anticonvulsant activity. Succinimide derivatives were obtained from a simple solvent-based reaction and a mechanochemical aza-Michael reaction of maleimide or its N-substituted derivatives with selected amines. The structure of the compounds was confirmed by spectroscopic methods (NMR, FT-IR, HPLC, ESI-MS, EA and XRD for four compounds). The cytotoxic activity of the succinimide derivatives was evaluated using HepG2 cells for hepatocytotoxicity and SH-SY5Y cells for neurocytotoxicity. None of the studied compounds showed hepatocytotoxicity and two showed neurocytotoxicity. Initial anticonvulsant screening was performed in mice using the psychomotor seizure test (6 Hz, 32 mA). The selected compounds were evaluated in the following acute models of epilepsy: the maximal electroshock test, psychomotor seizure test (6 Hz, 44 mA), subcutaneous pentylenetetrazole seizure test, and acute neurotoxicity (rotarod test). The most active compound 3-((4-chlorophenyl)amino)pyrrolidine-2,5-dione revealed antiseizure activity in all seizure models (including pharmacoresistant seizures) and showed better median effective doses (ED50) and protective index values than the reference compound, ethosuximide. Furthermore, 3-(benzylamino)pyrrolidine-2,5-dione and 3-(phenylamino)pyrrolidine-2,5-dione exhibited antiseizure activity in the 6 Hz and MES tests, and 3-(butylamino)−1-phenylpyrrolidine-2,5-dione and 3-(benzylamino)−1-phenylpyrrolidine-2,5-dione exhibited antiseizure activity in the 6 Hz test. All active compounds demonstrated low in vivo neurotoxicity in the rotarod test and yielded favourable protective indices.

Ethno-botanical Verification and Phytochemical Profile of Ethanolic leaves Extract of Two Medicinal Plants (Phragmenthera capitata and Lantana camara) used in Nigeria using GC- MS Technique

Background: The present experiment was designed to determine the bioactive constituents from extracts of leaves of Phragmenthera capitata and Latana camara. The medicinal value of a plant species is dependent upon its various phytochemical constituents. Methodology:The chemical compositions of the ethanolic extract of the leaves of P. capitata and L. camara were investigated using theGas Chromatography-Mass spectrometry model GCMS-QP2010 PLUS SHIMADZU. The column used was aPerkin Elmer Elite – 5 capillary columns measuring 30m × 0.25mm with a film thickness of 0.25mm composed of 95% Dimethylpolysiloxane. The carrier gas used was Helium at a flow rate of 0.5ml / min. Results:Fifteen (15) bioactive phytochemical compounds were identified for P. capitata and twenty (20) bioactive phytochemical compounds were identified for L. camara. The prevailing compounds in P. capitata were, 3-H-pyrazol-3-1, Decanoic acid, n-Hexadecanoic acid, Pentanoic acid, Methyloctanoic acid, 4-octanoicacid, 15 -tetraosenoic acid, oleic acid, Octadecanoic acid, Pentafluoropropronic acid, (E)-13-docosenoic acid, Vitamin E, Lupeol and Chilosyphone. Also, in L. camara the following compounds were identified, 3-n-hexythiolane, Docosanoic acid, 1- nonanol, 1-hexacosanol, Divalonic acid, Decanoic acid, Octanoic acid, Eicosanoic acid, Hexadecanoic acid, Nonadecanoic acid, 9-12 octadecanoic acid, 11 -octadecadienoic acid, Pentadecanoic acid, Oleic acid, Methyl -Beta-D-arabinopyranoside, Acetic acid, Pentanoic acid, Heneicosanoic acid, methyl ester and 2H-pyran,2-(7-heptadecynloxytetrahydro. Conclusion: Based on the results of findings, it could be concluded that extract from P. capitata and L. camara may have antioxidant, antimicrobial, anti-cancer, anti-diabetic, anti-fungal and anti-convulsant activities due to the presence of secondary metabolites in the ethanolic extract

In-silico Studies of Quinazolinone Analogues to Distinguish their Hypothetical Binding Mode using the X-ray crystal Structure Human carbon Anhydrase II (HCAII) Enzyme Complex with Sugar Sulfamate for Anticonvulsant Activity

The quinazolinone moiety is a significant pharmacophore that depicts various types of pharmacological activities as shown in recent exhaustive ligatures. Quinazolinone exhibit potent central nervous system (CNS) activities like anti-anxiety, analgesic, anti-inflammatory and anticonvulsant. To develop these views and application profiles, attempt have been made to report a drug/ligand or receptor/protein interactions by identifying the suitable active site against X-ray crystal structure of Human Carbonic Anhydrase II (HCA II) enzyme for anticonvulsant activity using Vlife MDS version 4.6 Software because the protein-ligand interaction plays a significant role in structural based drug designing. The interaction was evaluated based on the score comparison between quinazolinone derivatives with sugar sulfamate. The quinazolinone ring forms hydrophobic and hydrogen bond contacts amino acid residues. The ligands 4t and 4s were shown to possess minimum dock score i.e. minimum binding energy in Kcal/mole i.e. these molecules has more affinity for the active site of the receptor. Molecules with low dock score and binding energy show more affinity towards the receptor. The data reported in this article may be helpful for the medicinal chemists who are working in this area.

Validated LC-MS/MS method for quantitation of solasodine in rat urine and feces: Blocking nonspecific adsorption

AbstractSolasodine, a steroidal alkaloid, is distributed extensively in Solanaceae plants with multiple biological activities such as neuroprotection, antineoplastic and anticonvulsant activities. However, there is little information about the excretion of intact solasodine in vivo. To investigate its excretion, a reliable LC-MS/MS method for quantitation solasodine in rat urine and feces was established and validated. Sample preparation was carried out by liquid-liquid extraction using MTBE as extractant. Moreover, rat urine was preconditioned with BSA, an anti-adsorptive additive, to prevent the nonspecific binding of solasodine to containers and tubes. The method was validated over the range of 4–2000 ng mL−1. The correlation coefficient (r2) were all above 0.999. The intra- and inter-day precision and accuracy were within 16.9% and between −11.0 and 8.9%, respectively. The recovery of solasodine in urine and feces was in the range of 72.5–80.3 and 75.7–80.2%, respectively. IS-normalized matrix factor ranged from 0.94 to 1.12 with RSD% ≤4.02%. This method was successfully applied to the excretion study of solasodine following oral and intravenous administration.

Behavioral Effects and Analgesic Profile of Hemoglobin-Derived Valorphin and Its Synthetic Analog in Rodents.

Valorphin (V1) is a naturally occurring peptide derived from hemoglobin that has been found to have an affinity for opioid receptors and exhibits antinociceptive and anticonvulsant activity. Some of its synthetic analogs containing an aminophosphonate moiety show structure-dependent potent antinociceptive effects. This study aimed to reveal a detailed picture of the antinociceptive mechanisms and behavioral effects of V1 and its recently synthesized phosphopeptide analog V2p in rodents using a range of methods. The studied peptides significantly reduced acute (mean V1-9.0, V2p-5.8 vs. controls-54.1 s) and inflammatory (mean V1-57.9 and V2p-53.3 vs. controls-107.6 s) nociceptive pain in the formalin test, as well as carrageenan-induced hyperalgesia (mean V1-184.7 and V2p-107.3 vs. controls-61.8 g) in the paw pressure test. These effects are mediated by activation of opioid receptors with a predominance of kappa in V1 antinociception and by delta, kappa, and mu receptors in V2p-induced antinociception. Both peptides did not change the levels of TNF-alpha and IL-1-beta in blood serum. V1 induces depression-like behavior, and V2p shows a tendency toward anxiolysis and short-term impairment of motor coordination without affecting exploratory behavior. The results characterize valorphin and its derivative as promising analgesics that exert their effects both centrally and peripherally, without causing severe behavioral changes in experimental animals. These encouraging data are a foundation for future studies focusing on the effects of hemorphins after long-term treatment.

Medicinal Attributes of Pyrazoline in Drug Discovery

Abstract: Pyrazoline are structurally versatile nitrogen-containing heterocycle that has gained more attention owing to its diversified pharmacological activities. This special scaffold serves as a fundamental component in a variety of bioactive chemicals, enabling the creation of new molecules with advantageous biological functions. The present review paper provides a summary of diversified pharmacological activities in particular, anticancer, antimalarial, antimicrobial, antifungal, antidepressant, anti-inflammatory, antinociceptive, antitubercular, anticonvulsant, anti-amoebic, antischistosomal, insecticidal, hypotensive, antiviral, antioxidant and anti-trypanosomal activity. This review also presents numerous simple synthetic techniques for the preparation of pyrazolines and also highlights the applicability of pyrazoline in drug discovery.

Designing novel piperine-vanillin nano-crystals for bioavailability enhancement

Piperine (PIP) exhibits various pharmacological effects including anti-inflammatory, antipyretic, anti-convulsant, and neuroprotective activity, but its poor water solubility and oral absorption limit its therapeutic uses. In the present study, nano-crystal technology was employed to enhance the dissolution rate and bioavailability of PIP. Piperine-vanillin (PIP-VN) nano-crystals were formulated by top-down and bottom-up techniques and evaluated both in vitro and in vivo. The results revealed that the PIP-VN nano-crystal exhibited an average particle size of 34.03 ± 0.51 nm. In the release study, PIP-VN nano-crystal performed 2.63-fold enhancement than PIP coarse powder. Upon oral administration, in the brain AUC0–24 of PIP-VN nano-crystal was significantly higher than PIP suspension. The brain/blood ratio of the drug for PIP-VN nano-crystal was higher than PIP suspension; indicating that administration of PIP-VN nano-crystal was superior for the delivery drug to the brain. PIP-VN nano-crystal showed AUC0–24 of 5.654 ± 0.230 ngh/mL in the brain which was more than PIP suspension (AUC0–24 of 2.025 ± 0.009 ngh/mL in the brain). From AUC data it may be concluded that brain delivery efficiency was improved using the nano-crystal approach. Compared with PIP coarse powder PIP-VN nano-crystals exhibit excellent performance in both in vitro and in vivo studies.

Synthesis, in vivo Biological Evaluation and Molecular Docking Study of Some Newer Oxadiazole Derivatives as Anticonvulsant, Antibacterial and Analgesic Agents.

The compounds containing heterocyclic cores with O, N and/or S atoms are bioactive and valuable molecules in the field of drug discovery and development. There are several applications in different areas for the molecules having oxadiazole moiety in their structures viz. herbicides and corrosion inhibitors, electron-transport materials, polymers and luminescent materials. Hence, demand for new anticonvulsant, antibacterial and analgesic agents has turned into an imperative assignment in the area of medicinal chemistry to improve therapeutic efficacy as well as safety. In the journey of new anticonvulsive, antibacterial and analgesic molecules with better potency, some newer Oxadiazole analogues were attained by a sequence of synthetic steps with the substituted acrylic acids. IR and 1H-NMR spectral data were used for the structure elucidation of obtained chemical compounds. In this perspective, the anticonvulsant, antibacterial and analgesic activities were evaluated for synthetically obtained newer chemical moieties. Furthermore, a molecular docking study was performed to elucidate the binding modes of synthesized ligands in the active pockets of Cox-1/2 enzymes, DNA Gyrase and GABA inhibitors. It has been observed that all the synthetic molecules showed good analgesic activity while A1 molecule demonstrated better analgesic activity. In the case of anticonvulsant and antibacterial activity among other ligands, C1 molecule possessed profound anticonvulsant activity whereas B1 molecule showed maximum antibacterial activity and molecular docking study also endorsed the same consequences. It might be recognized from the present study that prepared compounds are distinctive in lieu of their structure and noticeable biological activity. In the quest for a newer group of anticonvulsant, antibacterial and analgesic molecules, these compounds might be useful for the society.

Differential impact of a ghrelin receptor antagonist or inverse agonist in the electrical kindling model of epilepsy

Ghrelin is a peptide, which has been shown to affect seizures. However, there is not a consensus about its real impact on the control of seizure severity. We assessed the influence of intra-amygdala injections of a ghrelin receptor (GHSR) antagonist, as well as a GHSR inverse agonist on the electrical kindling-induced seizures. Two unipolar electrodes and a tripolar electrode twisted with a guide cannula were implanted in the skull surface or the basolateral amygdala of adult male rats, respectively. A rapid electrical kindling protocol was applied for kindling epileptogenesis. The stimulations were applied until rats showed three consecutive stage five seizures. Each rat was considered as its control. D-Lys-3-GHRP-6 (1, 12.5, and 25 μg/rat) or [D-Arg, D-phe, D-Trp, heu] substance P (D-SP) (50, 500 and 5000 ng/rat) as the GHSR antagonist or inverse agonist were injected into the basolateral amygdala. Seizure parameters including after-discharge duration (ADD), stage five duration (S5D), and seizure stage (SS) were documented thirty minutes following administration of the drugs or saline. Antagonism of the GHSR in the amygdala, significantly increased seizure induction in the kindled rats, in a dose-dependent manner, and induced spontaneous seizures leading to status epilepticus. Conversely, D-SP had a dose-dependent anticonvulsant activity, indicated by decreased ADD and S5D. The results show that GHSR inverse agonism suppressed seizure severity in the rat amygdala kindling model, whereas GHSR antagonism made seizures more severe. Therefore, when considering the ghrelin system to modulate seizures, it is crucial to note the differential impact of various GHSR ligands.

A Comprehensive Review of Essential Oils and Their Pharmacological Activities in Neurological Disorders: Exploring Neuroprotective Potential.

Numerous studies have demonstrated essential oils' diverse chemical compositions and pharmacological properties encompassing antinociceptive, anxiolytic-like, and anticonvulsant activities, among other notable effects. The utilization of essential oils, whether inhaled, orally ingested, or applied topically, has commonly been employed as adjunctive therapy for individuals experiencing anxiety, insomnia, convulsions, pain, and cognitive impairment. The utilization of synthetic medications in the treatment of various disorders and symptoms is associated with a wide array of negative consequences. Consequently, numerous research groups across the globe have been prompted to explore the efficacy of natural alternatives such as essential oils. This review provides a comprehensive overview of the existing literature on the pharmacological properties of essential oils and their derived compounds and the underlying mechanisms responsible for these observed effects. The primary emphasis is on essential oils and their constituents, specifically targeting the nervous system and exhibiting significant potential in treating neurodegenerative disorders. The current state of research in this field is characterized by its preliminary nature, highlighting the necessity for a more comprehensive overlook of the therapeutic advantages of essential oils and their components. Integrating essential oils into conventional therapies can enhance the effectiveness of comprehensive treatment regimens for neurodegenerative diseases, offering a more holistic approach to addressing the multifaceted nature of these conditions.

The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats

BackgroundStatus epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures.MethodsTwenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated.ResultsCentella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments.ConclusionThe dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

Preparation and Evaluation of Primidone Solid Lipid Nanoparticle for Alleviating Seizure Activity in Wistar Rats

Introduction: In order to increase primidone’s anticonvulsant action, the study set out to manufacture it in solid lipid nanoparticle form (PRI-SLN). Method: Microemulsification and ultrasonication procedures were used to create 17 PRI-SLN formulations. Results: The PRI-SLN displayed a high entrapment efficiency (46.37 ± 2.42% to 81.82 ± 1.21%), as well as small particle size (149.9 ± 6.72 to 188.8 ± 5.25 nm). According to the in-vitro release study, PRI from SLNs releases more slowly than PRI by itself. The thermal analysis showed the drug’s compatibility with other substances and its presence in the more soluble amorphous state. Following a lethal and chronic dosage of picrotoxin, the PRI-SLN exhibited a higher anticonvulsant efficacy, according to in-vivo research on rats (p< 0.05). Conclusion: SLN with stronger anticonvulsant action can be made from PRI.

Molecular Docking Studies and ADME Prediction of Benzimidazole Derivatives on Anti-convulsant Activity by Inhibiting Voltage-Gated Sodium Channel (NavMs)-5HVX

Molecular Docking Studies and ADME Prediction of Benzimidazole Derivatives on Anti-convulsant Activity by Inhibiting Voltage-Gated Sodium Channel (NavMs)-5HVX

Synthesis and Anti-convulsant Activity of 1-[3-(4-Amin ophenyl)-3-Oxopropanoyl]- 5,5-Diphenyl imidazolidine -2,4-Dione and its Derivatives

Synthesis and Anti-convulsant Activity of 1-[3-(4-Amin ophenyl)-3-Oxopropanoyl]- 5,5-Diphenyl imidazolidine -2,4-Dione and its Derivatives

Novel hydantoin derivatives: Synthesis and biological activity evaluation

Novel compounds derived from hydantoin were synthesized using a chloroacetyl chloride linker in conjunction with terminal compounds of sulphonamides and amines. The compounds were subjected to various analytical techniques, including LC-MS/MS, 1H NMR, 13C NMR, FT-IR, and determination of melting point. Subsequently, the synthesized compounds were evaluated for their potential anti-cancer properties (against) breast cancer (MCF-7) and lung cancer (A549) cell lines by the MTT assay. Additionally, the compounds' anticonvulsant activity was assessed using pentylenetetrazol (PTZ)-induced seizure in mice. Furthermore, the inhibitory activity of selected compounds against the PI3Kα enzyme at a concentration of 100 µM was investigated. The biological evaluation of the compounds did not show the expected anticonvulsant effect when tested at various doses (5, 10, and 20 mg/kg b.w using the intraperitoneal injection), with all mice showing a seizure score of 5. MTT assay showed moderate anti-cancer activity against, the (A549) cell line, with compound 37 exhibiting the highest inhibition of cell viability at 55.1%. In the case of the breast cancer cell line, compounds 37, 40, 42, and 45 demonstrated inhibition percentages ranging from 64% to 74%. Moreover, the compounds displayed a relatively limited inhibitory effect on PI3Kα activity during the in-vitro evaluation compared to staurosporine. These findings suggest that further optimization and modification of the synthesized compounds may be necessary to enhance their anticonvulsant and anti-cancer properties, particularly regarding PI3Kα inhibition.

GABA–AT Inhibitors: Design, Synthesis, Pharmacological Characterization, Molecular Docking and ADMET Studies

Abstractγ‐aminobutyric acid (GABA) is the main neuroinhibitory transmitter and a non‐proteinogenic amino acid in the brain. When the brain concentration of GABA diminishes below a threshold level, it can cause excess neuronal excitation and lead to convulsions. γ‐Aminobutyric acid aminotransferase (GABA‐AT) is an enzyme that catalyzes the conversion of GABA to succinic semialdehyde in the GABA shunt pathway and responsible for breaking down GABA in the brain. By inhibiting GABA‐AT activity, it may be possible to increase the levels of GABA in the brain and reduce the likelihood of seizures. Herein, the synthesis and evaluation of α‐pyrazolo‐(aryl/alkyl)methyl‐ketone and pyrazolo[5,1‐a]isoquinoline derivatives were carried out anticonvulsant activity, with a focusing on GABA‐AT inhibition. In total, 20 novel compounds were synthesized, and characterized with binding assays at GABA‐AT receptor, in the 0.060±0.01 to 5.99±0.10 micromolar range. The ADMET predictions and drug‐like characteristics of α‐pyrazolo‐(aryl/alkyl)methyl‐ketone and pyrazolo[5,1‐a]isoquinoline compounds were identified by pharmacokinetic investigations. Furthermore, the predicted analogue‐enzyme complexes with docking scores were in the range of −7.3 to −10.5, and their SAR analysis was found to be significant of α‐pyrazolo‐(aryl/alkyl)methyl‐ketone and pyrazolo[5,1‐a]isoquinoline structures in medicinal chemistry. Our results revealed that this new structural information will be useful for the future design and synthesis of activity‐based GABA‐AT inhibitors.

Evaluation of anticonvulsant activity of Bixa Orellana Linn. seed

Evaluation of anticonvulsant activity of Bixa Orellana Linn. seed

Evaluation of the anticonvulsant activity of ethanol leaf extract of Panicum maximum in pentylenetetrazole and strychnine induced seizure in mice.

Epilepsy is a chronic neurological condition affecting around 50 million people worldwide. This study evaluated the anticonvulsant effect of Panicium maxmium in pentylenetetrazole (PTZ) and strychnine (STN) induced convulsions in mice. For each model, 25 mice were divided into five groups; group 1 received 10 ml/kg distilled water, groups 2-4 received 100 mg/kg, 200 mg/kg and 400 mg/kg of extract p.o respectively. Group 5 received 3 mg/kg of diazepam p.o. Convulsion was induced intraperitoneally using PTZ and STN, thirty minutes after the extract was administered. The onset of myoclonic, tonic-clonic seizure, time of death within 60 minutes of PTZ and STN administration were monitored. Data were statistically analyzed using one-way ANOVA followed by Dunnet’s comparison tests. In STN-induced seizure model, 100 mg/kg of P. maximum exhibited a significant (p < 0.001) anticonvulsant activity by delaying myoclonic seizure onset in mice when compared to the control. Significant (p < 0.001) activity was also observed in the onset of tonic clonic seizure at same dose when compared to control. In PTZ-induced seizure model, 200 mg/kg exhibited more significant (p < 0.001) activity followed by 100 mg/kg (p < 0.05) by delaying myoclonic seizure onset in mice when compared to the control. Significant (p < 0.001) activity were observed in tonic clonic phase at same doses respectively. The different doses administered couldn’t protect the mice from death. Diazepam, standard drug used, protected all the animals without any signs of convulsions. The results provide evidence that the extract possesses anticonvulsant activity.