ANTICONVULSANT POTENCY OF 10 VARIOUS P-ISOPROPOXYPHENYLSUCCINIMIDE DERIVATIVES IN THE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE THRESHOLD MODEL IN MICE

Multiple quantitative trait locus (QTL) mapping studies designed to localize seizure susceptibility genes in C57BL/6 (B6, seizure resistant) and DBA/2 (D2, seizure susceptible) mice have detected a significant effect originating from midchromosome 5. To confirm the presence and refine the position of the chromosome 5 QTL for maximal electroshock seizure threshold (MEST), reciprocal congenic strains between B6 and D2 mice were created by a DNA marker-assisted backcross breeding strategy and studied with respect to changes in MEST. A genomic interval delimited by marker D5Mit75 (proximal to the acromere) and D5Mit403 (distal to the acromere) was introgressed for 10 generations. A set of chromosome 5 congenic strains produced by an independent laboratory was also studied. Comparison of MEST between congenic and control (parental genetic background) mice indicates that genes influencing this trait were captured in all strains. Thus, mice from strains having D2 alleles from chromosome 5 on a B6 genetic background exhibit significantly lower MEST compared with control littermates, whereas congenic mice harboring B6 chromosome 5 alleles on a D2 genetic background exhibit significantly higher MEST compared with control littermates. Combining data from all congenic strains, we conclude that the gene(s) underlying the chromosome 5 QTL for MEST resides in the interval between D5Mit108 (26 cM) and D5Mit278 (61 cM). Generation of interval-specific congenic strains from the primary congenic strains described here may be used to achieve high-resolution mapping of the chromosome 5 gene(s) that contributes to the large difference in seizure susceptibility between B6 and D2 mice.

Download Full-text

Fluoxetine enhances maximal electroshock seizure threshold in Albino rat model when compared to phenytoin

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20175689 ◽

2017 ◽

Vol 7 (1) ◽

pp. 138 ◽

Cited By ~ 1

Author(s):

Tanmoy Gangopadhyay ◽

Ananya Mandal ◽

Uma Shanker Keshri

Keyword(s):

Seizure Threshold ◽

Albino Rats ◽

P Value ◽

Anticonvulsant Effect ◽

Maximal Electroshock ◽

Maximal Electroshock Seizure ◽

Albino Rat ◽

Co Morbidity ◽

Significant Difference ◽

Electroconvulsive Seizure

Background: Individuals with epilepsy have a higher incidence of psychiatric disorders than person without epilepsy. Epidemiological studies have shown that the co-morbidity of epilepsy and depression to be high as 50%. The conventional anti-depressants are believed to lower the seizure threshold making it difficult to treat the co-morbid depression, but animal studies have shown SSRIs, a common anti-depressant, to have anti-convulsant properties. So, we propose to study the anticonvulsant effects of fluoxetine, a SSRI, in albino rats against maximal electroshock seizure and to compare against a standard antiepileptic drug phenytoin.Methods: The anticonvulsant effect of fluoxetine was observed in model of maximal electroconvulsive seizure threshold in albino rats. The animals were divided into 3 groups having 6 animals each, receiving distilled water, fluoxetine and phenytoin respectively. The drugs were given orally, and the effect was observed on day 7, 14 and 21. Tonic hind-limb extension was taken as the parameter of electroshock seizure. The effects were compared against a standard anti-seizure drug phenytoin.Results: Fluoxetine showed significant elevation of the seizure threshold following 14 days of administration (P value 0.031). The effect was comparable to phenytoin with no significant difference after 7, 14 and 21 days of treatment (P-value 0.485, 0.699 and 0.818 respectively) though phenytoin showed significant anti-seizure effect since day 7 of treatment.Conclusions: Fluoxetine showed significant anti-seizure activity against electroconvulsive seizure in albino rats.

Download Full-text

Comparison of the anticonvulsant potency of various diuretic drugs in the maximal electroshock-induced seizure threshold test in mice

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/68694 ◽

2018 ◽

Vol 27 (5) ◽

pp. 609-613 ◽

Cited By ~ 3

Author(s):

Katarzyna Załuska ◽

Maria Kondrat-Wróbel ◽

Jarogniew Łuszczki

Keyword(s):

Seizure Threshold ◽

Maximal Electroshock ◽

Threshold Test ◽

Diuretic Drugs

Download Full-text

Discovery of novel substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)-2-(4-chloro-phenoxy)-acetamide for biphasic anticancer and anticonvulsant activities

Medicinal Chemistry ◽

10.2174/1573406415666191206101617 ◽

2019 ◽

Vol 15 ◽

Cited By ~ 1

Author(s):

Divya Chauhan ◽

Syed Riaz Hashim ◽

Priyanka Rani ◽

Sushil Kumar ◽

Navratan Shrimal ◽

...

Keyword(s):

Wistar Rats ◽

Computational Study ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Pharmacokinetic Profile ◽

Seizure Threshold ◽

Anticonvulsant Effect ◽

Maximal Electroshock ◽

Maximal Electroshock Seizure ◽

Ht 29

Background : Privileged 4H-chromenes possess the potent anticancer and anticonvulsant actives. By inspiring potency of 4H-chromenes and demands of present era of scaffold, discovery of effective molecule was carried out for the treatment of cancer and conversant. Objective : Designed and synthesized a novel series of 4H-chromene derivatives from one port synthesis for the treatment of cancer and conversant. Method : Substitution of side amide chain was formed in multiple steps on amine group of chromene. Later, anticancer activity of synthesized compounds was investigated against human colon adenocarcinoma cell line (HT-29) using sulforhodamine B (SRB) assay. Moreover, anticonvulsant activity was also screened out by using maximal electroshock seizure (MES) model and subcutaneous Metrazol Seizure Threshold Test (scMET) in albino Wistar rats. Neurotoxicity was evaluated using by rotarod test. Before the synthesis, docking studies were performed using various molecular targets. Subsequently, the computational study of the titled compounds was performed to predict the pharmacokinetic profile. Result: Among the fifteen tested compounds, A4 and A9 were found to be active against HT-29 cells (growth inhibitory dose 50% (GI50) <11µM). Moreover, compounds A4 showed the protection at 300mg/kg in scMET (h) for albino Wistar rats and compounds A9, A11, A15 exhibited the anticonvulsant effect at the doses 100, 300 and 300 mg/kg, respectively in MES screen(h). Conclusion : Due to these encouraging results, we concluded that both A4 and A9 may be effective against colon cancer. While compound A9 may be used as a considerable effective molecule for the treatment of epilepsy.

Download Full-text

The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs

Pharmacological Research ◽

10.1016/j.phrs.2013.09.003 ◽

2013 ◽

Vol 77 ◽

pp. 39-46 ◽

Cited By ~ 20

Author(s):

Wolfgang Löscher ◽

Katrin Hoffmann ◽

Friederike Twele ◽

Heidrun Potschka ◽

Kathrin Töllner

Keyword(s):

Antiepileptic Drug ◽

Threshold Model ◽

Seizure Threshold ◽

The Novel

Download Full-text

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

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20195590 ◽

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.

Download Full-text

Synthesis and Anticonvulsant Activity of α-Amino Acid Amide Derivatives

Current Bioactive Compounds ◽

10.2174/1573407214666180530081328 ◽

2019 ◽

Vol 15 (5) ◽

pp. 547-561

Author(s):

Valerie Currier ◽

Maryam Molki ◽

Katelyn Fryman ◽

Lacey D. Rodgers ◽

A. Michael Crider

Keyword(s):

Amino Acid ◽

Side Effects ◽

Anticonvulsant Activity ◽

Acid Amide ◽

New Drugs ◽

Seizure Threshold ◽

Maximal Electroshock ◽

Maximal Electroshock Seizure ◽

Maximal Electroshock Seizure Test ◽

Amide Derivatives

Background: Epilepsy is a disease of the central nervous system that affects approximately 50 million individuals worldwide. Although several new drugs have been marketed in the last 25 years, almost one-third of patients are not protected. In many cases, currently available drugs produce undesirable side effects. As a result, a need exists for novel anticonvulsants with unique mechanisms of action and minimal side effects. Methods: A mixed anhydride coupling procedure and standard deprotection procedures were utilized to prepare 36 α-amino acid amides. All final products were evaluated in mice and rats utilizing a standard battery of anticonvulsant tests. Results: α-Amino acids containing a 2,6-dimethylanilide group exhibited anticonvulsant activity in the maximal electroshock seizure test and 6 Hz test in mice and rats. A small, branched-chain on the α- carbon generally maintained or enhanced anticonvulsant activity in the maximal electroshock seizure test. The (R)-α-amino acid amides were typically more potent and slightly more neurotoxic than the corresponding (S)-enantiomers. The valine dimethylanilide (R)-42 was highly active in the MES test in mice (ED50 = 3.6mg/kg) and rats (ED50 = 3.8 mg/kg). (R)-42 also demonstrated excellent anticonvulsant activity in the 6 Hz, picrotoxin, and corneal kindled mouse tests. Furthermore, (R)-42 did not lower seizure threshold when evaluated in the intravenous metrazol seizure test. Conclusion: α-Amino acid 2,6-dimethylanilides exhibited potent activity in a variety of anticonvulsant tests in mice and rats. The valine derivative (R)-42 represents a promising compound for potential use in complex partial seizures.

Download Full-text