scholarly journals Synthesis and Evaluation of Antiepileptic Activity of Newly Designed Coumarin-Sulfonamide Hybrids

2021 ◽  
Vol 33 (12) ◽  
pp. 3108-3114
Author(s):  
Arti Gupta ◽  
Sandeep Kumar ◽  
Vijay Kumar Singh ◽  
B.P. Mallikarjun ◽  
Neerupma Dhiman ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Knoevenagel Condensation ◽  
Histopathological Study ◽  
Maximal Electroshock ◽  
Significant Protection ◽  
New Approach ◽  
Antiepileptic Activity ◽  
Hybrid Compounds ◽  
Seizure Models ◽  
Coumarin Ring

The combination of different heterocyclic rings to form a multifunctional compound is a new approach to get the potent and selective compounds, which can act as antiepileptic drugs. In this study we designed and synthesized the hybrid of the coumarin ring with sulfonamide moiety. Coumarin sulfonamide hybrids (CS1-CS7) were synthesized by Knoevenagel condensation of methyl anilinosulfonyl acetate with substituted salicyaldehyde in the presence of catalytic base. The synthesized hybrid compounds were characterized by means of mass, 1H & 13C NMR and FTIR spectroscopy, moreover antiepileptic activity was screened through seizure model of epilepsy using pentylenetetrazole and maximal electroshock. According to results, compound CS-2 remained to be highest potent and presented significant protection at 60 mg/kg in both the seizure models. Furthermore, compound CS-2 was also evaluated for biochemical and a histopathological study in which no significant results were obtained. In addition to former activities, compound CS-2 was also examined for liver toxicity.

scholarly journals Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides

2021 ◽  
Vol 22 (23) ◽  
pp. 13092
Author(s):  
Michał Abram ◽  
Marcin Jakubiec ◽  
Anna Rapacz ◽  
Szczepan Mogilski ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Water Soluble ◽  
Calcium Currents ◽  
In Vitro Studies ◽  
Maximal Electroshock ◽  
Induction Effect ◽  
Potential Candidate ◽  
Seizure Models ◽  
Seizure Model

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.

scholarly journals A Review on anti-epileptic activity of seaweed Ecklonia cava

2019 ◽  
Vol 9 (1-s) ◽  
pp. 425-432 ◽  
Author(s):  
Samiat Abimbola Owoalade ◽  
Diana Moria Martin Lou ◽  
Kashikant Yadav ◽  
Sumitra Poudel
Keyword(s):  
Anticonvulsant Activity ◽  
Wistar Rats ◽  
Wistar Rat ◽  
Epileptic Activity ◽  
Ecklonia Cava ◽  
Laboratory Animals ◽  
Maximal Electroshock ◽  
Antiepileptic Activity ◽  
Chemically Induced ◽  
Experimental Laboratory

The Present study was undertaken to investigate the Anticonvulsant activity of sea weed extract of Ecklonia cava on electrically and chemically induced seizures in wistar rat. The methanolic seaweed extract was studied for its anticonvulsant activity by using experimental paradigms like Maximal electroshock-induced seizures (MES). Expected to exhibited protection against tonic convulsions induced by MES in wistar rats. Objective of these studies were designed to screen the antiepileptic activity of the seaweed Ecklonia cava in experimental laboratory animals. Keywords: Antiepileptic Activity, Ecklonia cava (E.C), seizures, Flexon, Hind Limb Extension, Electroencephalography (EEG)

scholarly journals EVALUATION OF THE ANTICONVULSANT EFFECT OF AQUEOUS EXTRACT OF CENTELLA ASIATICA IN ALBINO MICE

2017 ◽  
Vol 9 (2) ◽  
pp. 312
Author(s):  
Dipjyoti Deka ◽  
Pinaki Chakravarty ◽  
Ayan Purkayastha
Keyword(s):  
Aqueous Extract ◽  
Hind Limb ◽  
Centella Asiatica ◽  
Control Group ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Absence Seizures ◽  
Seizure Models ◽  
Clonic Convulsions ◽  
One Way Anova

<p><strong>Objective: </strong>To evaluate the antiepileptic activity of aqueous extract of <em>Centella asciatica</em> in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced convulsions. <strong></strong></p><p><strong>Methods</strong><strong>: </strong>The anticonvulsant activity of leaves of <em>Centella asciatica </em>(200 mg/kg and 400 mg/kg) in mice was assessed using MES and PTZ induced seizure models. Abolition of tonic hind limb extension (MES and PTZ) and increase in seizure latency (PTZ) when compared to control group, were taken as a measure of protection. Statistical analysis was done using one-way ANOVA followed by Tukey-Kramer multiple comparisons test. The test was considered to be significant at p&lt;0.05.</p><p><strong>Results</strong><strong>: </strong>The aqueous extract of <em>Centella asiatica</em> at a dose of 200 mg/kg has abolished tonic hind limb extension in 1 out of 6 animals in MES while there was no anticonvulsant action in PTZ convulsions. At a dose of 400 mg/kg body weight, the aqueous extract of <em>Centella asiatica</em> has shown a significant anticonvulsant effect against both MES and PTZ convulsions, where it has abolished tonic hind limb extension in 4 mice in MES method and in all 6 mices in PTZ method.</p><p><strong>Conclusion</strong><strong>: </strong>The aqueous extract of <em>Centella asiatica</em> showed efficacy in both MES and PTZ convulsions in mice at a dose of 400 mg/kg. Since the clinical correlates of MES seizures are tonic-clonic convulsions and correlates of PTZ seizures are absence seizures, the aqueous extract of <em>Centella asiatica</em> is likely to be useful in the treatment of tonic-clonic and absence seizures.</p>

scholarly journals The Search for New Anticonvulsants in a Group of (2,5-Dioxopyrrolidin-1-yl)(phenyl)Acetamides with Hybrid Structure—Synthesis and In Vivo/In Vitro Studies

2020 ◽  
Vol 21 (22) ◽  
pp. 8780
Author(s):  
Michał Abram ◽  
Marcin Jakubiec ◽  
Anna Rapacz ◽  
Szczepan Mogilski ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Coupling Reaction ◽  
Calcium Currents ◽  
Maximal Electroshock ◽  
Preclinical Development ◽  
Toxic Dose ◽  
Pain Model ◽  
Seizure Models

Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED50) MES = 45.6 mg/kg, ED50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD50) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development.

scholarly journals New TRPV1 Antagonists as Candidates for Effective Anticonvulsant and Antinociceptive Agents

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 30
Author(s):  
Kamiński ◽  
Jakubiec ◽  
Zagaja ◽  
Andres-Mach ◽  
Mogilski ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Epileptic Seizures ◽  
Maximal Electroshock ◽  
Neurogenic Pain ◽  
Mes Test ◽  
Trpv1 Receptors ◽  
Seizure Models ◽  
The Common ◽  
Drug Resistant Epilepsy ◽  
Patients With Epilepsy

Epilepsy is recognized as one of the most common neurological disorders with a high risk of drug resistance. Notably, about one-third of the patients with epilepsy are not responsive to pharmacological treatment. Thus, the search for new, more effective anticonvulsants with a novel mechanism of action is undoubtedly necessary. The most recent neurobiological studies implicate central TRPV1 receptors in the induction of epileptic seizures. Moreover, it is suggested that TRPV1 desensitization is one of the crucial mechanisms of action responsible for the anticonvulsant activity of cannabidiol (CBD), which was proven to be effective against drug-resistant epilepsy. Bearing in mind the aforementioned facts, we developed in our recent studies a series of chemically original TRPV1 antagonists. Their structures were designed as integrated hybrids that join on the common chemical template the structural fragments of anticonvulsants identified by our team in the previous studies and known TRPV1 antagonists (described in the literature). As a result, these compounds revealed potent anticonvulsant activity in the preclinical studies using the most widely employed animal seizure models, namely, the maximal electroshock (MES) test, and the psychomotor 6 Hz (32 mA and 44 mA) seizure model in mice. In addition, selected substances demonstrated potent effectiveness by decreasing pain responses in formalin-induced tonic pain, in capsaicin-induced neurogenic pain, as well as in oxaliplatin-induced neuropathic pain in mice.

scholarly journals STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

2019 ◽  
Vol 12 (1) ◽  
pp. 185
Author(s):  
Shipra Kaushik ◽  
Kalpana Gohain
Keyword(s):  
Normal Saline ◽  
Anticonvulsant Activity ◽  
Ethanolic Extract ◽  
Albino Rats ◽  
Acorus Calamus ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Onset Of Action ◽  
Electrical Shock ◽  
Seizure Models

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

scholarly journals Assessment of efficacy of promethazine on seizure activity and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats

2019 ◽  
Vol 9 (1) ◽  
pp. 42
Author(s):  
Vinod Shinde ◽  
Sandesh Warudkar
Keyword(s):  
Antiepileptic Drugs ◽  
Sodium Valproate ◽  
Animal Studies ◽  
Seizure Activity ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Significant Protection ◽  
H1 Receptor ◽  
Electroshock Seizures ◽  
Antihistaminic Drug

Background: Presently available antiepileptic drugs are effective in controlling seizures in more than half of patients of all epilepsy but use is often limited by adverse effects. H1 receptor antagonists, have a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats.Methods: The effect of promethazine (10 mg/kg) and its interactions with antiepileptic drugs lorazepam and sodium valproate was assessed by using maximal electroshock seizures (MES) and chemoshock pentylenetetrazol (PTZ) method.Results: Promethazine along with lorazepam and sodium valproate in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of promethazine alone and in combination with lorazepam and sodium valproate showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method. This shows dual behavior of promethazine on MES and PTZ induced seizures. 

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