RESULTS:
1 - 3 of 3 for ""maximal electroshock seizure""
Importance of Pharmacophore in Designing Anticonvulsant Agents
Drug design is one of the critical aspects of the drug development process. The present review focused on different heterocyclic molecules having anticonvulsant activity with structural diversity and common pharmacophoric features. For the first time (1995) Dimmock and his team introduced specific arrangements of three important pharmacophores for anticonvulsant activity. These pharmacophores include two hydrophobic binding sites and one hydrogen binding site. After a few years (2012) Pandeya modified Dimmock’s concept by adding one more pharmacophoric feature as an electron donor in the previously suggested pharmacophoric arrangement of the anticonvulsant. As a result numerous scientists designed anticonvulsant drugs based on Dimmock’s and Pandeya’s concept. In addition marketed anticonvulsant preparation containing Riluzole Phenobarbital Progabide Ralitoline etc. also holds the suggested pharmacophores by Dimmock and Pandeya’s pharmacophoric concept. This review mainly focuses on the compilation of reported scientific literature in the last decade on the pharmacophoric features of different heterocyclic anticonvulsants which will help develop new anticonvulsants.
Synthesis and Structure-Activity Relationship on Anticonvulsant Aryl Semicarbazones
Seven series of various substituted aryl semicarbazones were synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure threshold tests. A comprehensive structure-activity relationship was derived comparing the substituents on the aryl ring and in the carbimino terminal. Generally the order of activity was 4-F > 2-Br = 3-Br = 4-Cl > 4-CH3 > 4-Br > 3-Cl > 3- CH3 with respect to the primary aryl group. Most of the compounds exhibited activity both in the MES and scPTZ screens. The 4-fluorophenyl substituted semicarbazones (5a-5y) emerged as the most potent compounds exhibiting anticonvulsant activity in mouse intraperitoneal (i.p.) and rat per oral (p.o.) MES scPTZ and psychomotor seizure (6 Hz) screens.
Antiepileptic Impact of Isoindole-1,3-diones Compounds: An Updated Review on Diversified Synthesis and Modes of Action
Epilepsy is a growing concern for the scientific community globally as less than 80% of individuals experience reduced seizure severity with existing antiepileptic medications and the chances of relapses are very high with those medications. Therefore the existing problem requires more attention to unravel the chances of relapses and adverse effects of available medications. Isoindole-13-diones serve as a valuable scaffold with diverse biological activities including analgesic anti-inflammatory and hypolipidemic properties. This review will emphasize the antiepileptic behaviours of the Isoindole-13-diones with diversified synthetic procedures and modes of action. For this purpose an extensive literature survey was undertaken through different online platforms such as PubMed Web of Science Scopus SciFinder Google Scholar Science Direct etc. Some N-substituted Isoindole-13-diones have demonstrated promising anticonvulsant activity primarily by effectively blocking sodium channels. Epilepsy is often linked to channelopathies involving α and β-subunits and medications have specific mechanisms for binding with the α-subunit of the sodium channel. Analyzing the structural features of phenytoin carbamazepine and lamotrigine revealed that benzene or phenol substitution along with the addition of a chloro group enhances their activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) tests. This review focuses on the role of specific sodium channels in electrical signalling and neurological conditions emphasizing the significance of Isoindole-13-diones and their derivatives in designing potent anticonvulsant agents particularly in the development of selective sodium channel inhibitors.