Antiepileptic Drug Development Program

Context: Carissa edulis Vahl (Apocynaceae) is used in Nigerian folk medicine to manage a plethora of diseases including epilepsy, cancer, and inflammation; its efficacy is widely acclaimed among communities of northern Nigeria. Objective: This study establishes anticonvulsant activities of aqueous fraction of ethanol root bark extract of Carissa edulis (RAF) and sub-fractions (S1 and S2) in animal models. Materials and methods:We evaluated the acute toxicity of the RAF, S1 and S2, and the anticonvulsant activity using pentylenetetrazole (PTZ), picrotoxin, strychnine, N-methyl-Daspartate (NMDA), isoniazid (INH), and aminophylline-induced seizures in mice. Their effects on maximal electroshock (MES) and kindling-induced seizures were studied in chicks and in rats, respectively, and in the electrophysiological study. The doses used for RAF were 150, 300, and 600 mg/kg while S1 and S2 were 250, 500, and 1000 mg/kg. Both RAF and sub-fractions were administered once during the experiment. Results: The intraperitoneal LD 50 of the RAF was estimated to be 2222.61 mg/kg and that of the S1 and S2 were above 5000 mg/kg. RAF protected the mice by 50% while sub-fractions by 16.67% against PTZ-induced seizures. RAF offered 33.33 and 16.67% protection against strychnine and NMDA models, respectively. However, RAF offered 66.67-33.33% protections against aminophylline-induced seizures at doses of 150 and 600 mg/kg, but RAF, S1, and S2 had no effect on MES-induced seizures. Discussion and conclusion: Our results validate the use of the plant traditionally in the management of epilepsy, thus supporting the appraisal of biologically active components of this plant as antiepileptic agents.

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“…The method described by Porter et al (1984) was adopted in this study with modifications. Briefly, 30 mice were divided into five groups of six.…”

Section: Maximal Electroshock-induced Convulsion In Chicksmentioning

confidence: 99%

“…Abolition of tonic extension of the hind limbs within 30 min after strychnine administration was considered as an indicator for anticonvulsant effects (Porter et al, 1984).…”

Section: Maximal Electroshock-induced Convulsion In Chicksmentioning

confidence: 99%

Anticonvulsant activity of aqueous fraction ofCarissa edulisroot bark

Ya’u

Yaro

Malami

et al. 2015

Pharmaceutical Biology

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“…Preliminary anticonvulsant evaluation was done using reported procedures (Krall et al, 1978;Porter et al, 1984;Kupferberg, 1989). Male albino mice (CF-1 Strain, 18~25 g) and male albino rats (Sprague-Dawely, 100~150 g) were used as experimental animals.…”

Section: Pharmacologymentioning

confidence: 99%

Microwave-assisted synthesis, anticonvulsant activity and quantum mechanical modelling of N-(4-bromo-3-methylphenyl) semicarbazones

Mehta

Yogeeswari

Sriram

et al. 2007

J. Zhejiang Univ. - Sci. B

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Abstract:Objective: To study the effect of halo substitution on disubstituted aryl semicarbazones on the anticonvulsant potential and model the activity based on quantum mechanics. Methods: A series of twenty-six compounds of N 4 -(4-bromo-3-methylphenyl) semicarbazones were synthesized and evaluated for the anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential compounds were also tested in the subcutaneous strychnine (scSTY) and subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized compounds were tested for behavioral impairment and CNS (central nervous system) depression in mice. Quantum mechanical modelling was carried out on these compounds to gain understanding on the structural features essential for activity. Results: Some compounds possessed broad spectrum anticonvulsant activity as indicated by their effect in pentylenetetrazole, strychnine, picrotoxin and maximal electroshock seizures models in resemblance to other aryl semicarbazone derivatives reported earlier. The higher the difference in HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels was, the greater was the activity profile. Conclusion: The pharmacophoric requirements for compounds to exhibit anticonvulsant activity that includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an electron donor have been justified with the molecular orbital surface analysis of the synthesized compounds.

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“…The NMLDA test was performed according to the method described by Czuczwar et al (13). The other tests followed the procedures described by the National Institutes of Health (NIH) in the Anticonvulsant Drug Development Program (14). The evaluation of ED,, was determined as mentioned previously (12).…”

Section: Ndprotected Mice In the Mes Test 4 H After Intraperitoneal Imentioning

confidence: 99%

Anticonvulsant Activity of Pyrid‐3‐yl‐Sulfonyl Ureas and Thioureas

Masereel

Lambert²,

Dogné

et al. 1997

Epilepsia

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Summary:The N-[(4-cycloheptylaminopyrid-3-yl)sulfonyl]-N'-cycloheptyl urea, a neuroprotective agent, and 10 chemically related sulfonyl(thio)ureas were evaluated in the maximal electroshock seizure test in mice. This sulfonylurea, BM 27, and two stucturally related sulfonylthioureas, BM 11 and BM 34, emerged with a 50% effective dose (ED,,) of 2.87, 1.72, and 1.19 mg/kg, respectively. Their anticonvulsant profiles were found to be similar to that of phenytoin: active in the maximal electroshock seizure (MES) test and inactive in chemically induced seizures (pentetrazole, strychnine, bicuculline, picrotoxine, N-methyl-D,L-aspartic acid). These compounds exhibited a higher protective index and potency than those of phenytoin. Additional work remains necessary, however, to determine whether BM 27 is of clinical interest. Key Words: Sulfonylurea-Sulfonylthiourea-Epilepsy-Anticonvulsan-BM 34. N-[ (4-cycloheptylaminopyrid-3-yl)sulfonyl]-N'-cycbheptyl urea, called BM 27, (Table 1) is a sulfonylurea that exhibits neuroprotective properties against normobaric hypoxia in mice (0.1-1 mg/kg) and cerebral ischemia in gerbils (1-2.5 mg/kg) (1). It is structurally related to torasemide (a loop diuretic) acting, as does furosemide (2), by the inhibition of the Na+ 2 HC1-K+ cotransporter of the thick ascending limb of Henle's loop (3). The central properties of BM 27 probably can be attributed to its ability to inhibit the astrocytic Na+ 2 HC1-K+ cotransporter (1). As furosemide blocks kainic acid-induced electrical discharges recorded from cortex (4), and in view of the antiepileptic properties attributed to the neuroprotective agents such as the antagonists of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors (5-9), we investigated the anticonvulsant activity of BM 27 and some related substances. In this study, BM 27 and two sulphonylthioureas, BM 11 and BM 34, were selected to be tested in several classic anticonvulsant assays to define their pharmacologic profile. METHODS ChemistryAll compounds were synthesized as described previously (1). Their elemental analyses for C, H, N, and S were within 0.4% of the theoretic values. 'H-nuclear magnetic resonance (NMR) and IR spectra were in complete agreement with their chemical structure. LipophilicityThe lipophilicity of compounds (log P) was measured at pH 7.4 and expressed as the logarithm of their partition coefficient in the n-octanollphosphate buffer system. The log P of a series of standards chosen in a wide range of log P values (from +0.16 to +2.0) was determined by using the shake-flask method (10). As reported (1,l l), a reverse-phase high performance liquid chromatography system was used to determine their capacity factor (log k') which corresponds to log (~-t,)/t,)] where t, is the drug retention time and t, is the void volume. A calibration curve calculated from log P and log k' of standards was used to interpolate the log P of the studied compounds. Pharmacology Anticonvulsant activityAll compounds were administered to OF1 male mice (22-25 g; Iffa-Credo, Les Onci...

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Antiepileptic Drug Development Program

Cited by 451 publications

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Anticonvulsant activity of aqueous fraction ofCarissa edulisroot bark

Anticonvulsant activity of aqueous fraction ofCarissa edulisroot bark

Microwave-assisted synthesis, anticonvulsant activity and quantum mechanical modelling of N-(4-bromo-3-methylphenyl) semicarbazones

Anticonvulsant Activity of Pyrid‐3‐yl‐Sulfonyl Ureas and Thioureas

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