Pharmacological Activity of Pyrazole Derivatives as an Anticonvulsant for Benefit against Epilepsy

Introduction: Pediatric patients with epilepsy are prone to cognitive impairments during growth and long-term use of most antiepileptic drugs (AED). The affected children do not respond to conventional AED and may require novel drugs to manage the disease. Valproic acid, a first-line drug to treat epilepsy, is associated with serious side effects, which precludes its wider use. Thus, in the present study, we intended to develop novel substituted pyrazoles. Methods: The molecules were tested for anticonvulsive activity in Swiss albino mice via maximal electroshock seizure and subcutaneous pentylenetetrazole assays. The most potent molecule among the class was further assayed for its effect on behavioral and CNS depressant activity. The effect of the most potent compounds was also analyzed on various indices of oxidative stress and inflammation in mice. Results: The designed compounds showed significant anticonvulsive activity in mice revealing 7h as the most potent anticonvulsive agent. The most potent anticonvulsant molecule 7h further showed no behavioral alteration and considerable CNS depressant activity. It also reduces the level of oxidative stress and inflammation in the mice. Conclusion: Our study demonstrated utility of pyrazole derivatives as anticonvulsants against epilepsy.

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SCREENING OF ANTI-ANXIETY ACTIVITY OF UNRIPE FRUITS OF MUSA PARADISIACA LINN.

INDIAN DRUGS ◽

10.53879/id.49.09.p0033 ◽

2012 ◽

Vol 49 (09) ◽

pp. 33-35

Author(s):

C. S Hallikeri ◽

◽

S. D Joshi ◽

P Patil ◽

V. H Kulkarni ◽

...

Keyword(s):

Amino Acids ◽

Operant Behavior ◽

Albino Rats ◽

Alcoholic Extract ◽

Standard Drug ◽

Musa Paradisiaca ◽

Cns Depressant ◽

Phytochemical Investigation ◽

Cns Depressant Activity ◽

Unripe Fruits

The alcoholic extract of unripe fruits of Musa paradisiaca Linn. (Musaceae) was evaluated for antianxiety activity by using operant behavior (behavioral disinhibition) model of anxiety in albino rats. Phytochemical investigation of alcoholic extract revealed the presence of flavonoids, amino acids,vitamins and carbohydrates. Alcoholic extract showed significant anti-punishment and anti-frustration activities at dose level of 500 mg/kg/day for 5 days which is comparable to standard drug, diazepam 5mg/kg. The presence of amino acid and flavonoids in alcoholic extract could be attributed for the antianxiety and other CNS depressant activity.

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Pharmacological Screening for CNS Depression, Analgesic and Anti-inflammatory Potentials of Sonneratia caseolaris (Linn.) Barks in Different Solvent Fraction

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2019/v29i530251 ◽

2019 ◽

pp. 1-11

Author(s):

Mst. Shirajum Munira ◽

Syeda Naureen Ahmed ◽

Md. Siddiqul Islam ◽

Md. Shariful Islam ◽

Mst. Luthfun Nesa ◽

...

Keyword(s):

Late Phase ◽

Dependent Manner ◽

Paw Edema ◽

Superior Result ◽

Sonneratia Caseolaris ◽

Cns Depressant ◽

Anti Inflammatory ◽

Pharmacological Screening ◽

Cns Depressant Activity

Aims: Bark of different fractions of Sonneratia caseolaris (Linn.) (Sonneratiaceae) were screened for its analgesic, anti-inflammatory and CNS activities. Study Design: For the purpose of these experiments the extracts were subjected to an in-vivo study. Place and Duration of Study: The study was carried out in August 2014 in the Department of Pharmacy, Southeast University, Dhaka, Bangladesh. Methodology: Ethanolic (ETF), ethyl acetate (EAF), chloroform(CLF) and pet ether (PTF) fractions of bark of S. caseolaris were used to evaluate the analgesic activity using Acetic acid induced writhing and Formalin test. The same fractions were evaluated for anti-inflammatory activity using Carrageenan induced hind paw edema model. The CNS depressant activity was evaluated by Hole cross method. Two doses of 150 mg/kg and 300 mg/kg were used. Results: The different fractions produced significant (p<0.05) writhing inhibition at both doses and reduced the number of linking induced by formalin. Among these fractions the most potent activity was found in ETF about 79.40% (300 mg/kg) that was almost similar to standard Diclofenac-Na 82.78% (10 mg/kg), then EAF 74.59% followed by CLF 59.03% and PTF 52.45% at dose 300 mg/kg). In formalin-induced paw licking model, all fractions of S. caseolaris showed superior result in the late phase compare to the early phase .The same fractions of extracts caused significant (p<0.05) inhibition of carrageenan induced paw edema in a dose dependent manner. A statistically significant (p<0.05) locomotor activity was also observed. Conclusion: Our result revealed that all the extractives of S. caseolaris have noticeable analgesic, anti-inflammatory and CNS depressant activities.

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Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy

10.20944/preprints202110.0415.v1 ◽

2021 ◽

Author(s):

Christi Cho ◽

Maxwell Zeigler ◽

Stephanie Mizuno ◽

Richard S. Morrison ◽

Rheem Totah ◽

...

Keyword(s):

Hydrogen Sulfide ◽

Mouse Model ◽

Membrane Integrity ◽

Brain Homogenate ◽

Maximal Electroshock ◽

Maximal Electroshock Seizure ◽

Mitochondrial Stress ◽

Acute Seizures ◽

Related Proteins

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

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