• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.93-97
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• 1993

We have previously reported that an NADPH-dependent succinic semialdehyde reductase was purified homogeneously from bovine brain by several chromatographic procedures, and was found to be a monomeric protein with a molecular mass of 28 kDa (Cho et al., Eur. J. Biochem. 1993). Since succinic semialdehyde is an important intermediate in the ${\gamma}$-aminobutyrate(GABA) shunt and GABA level is associated with various forms of human neurological disorders, we have investigated the effects of anticonvulsant drugs on the succinic semialdehrde reductase. Among the drugs tested, sodium valproate and diphenylhydantoin inhibited the enzyme activity, while some other drugs, barbiturate and chlorpromazine, had no inhibitory effects on the enzyme activity. The purified enzyme was also injected as an immunogen into Balb/c mice to obtain monoclonal antibodies (mob) and several mobs to the protein were produced from the fusion experiments.

• Korean Journal of Pharmacognosy
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• v.29 no.3
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• pp.179-186
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• 1998

The fractions of Uncariae Ramulus et Uncus seemed to be closely related with the levels of amino acids and other components which concerns with formation and metabolism of neurotransmitters in brain. The pretreatments of methanolic extract and its fractions prohibited the pentylenetetrazole (PTZ) induced convulsion. In such cases, lowered levels of ${\gamma}-aminobutyric$ acid and glutathione in brain were significantly recovered. And also the increased levels or activities of lipid peroxide, ${\gamma}-aminobutyric$ acid aminotransferase, xanthine oxidase, aldehyde oxidase, superoxide dismutase, catalase and glutathione peroxidase by PTZ-convulsion were lowered to normal state.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3318-3326
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• 2010

Five new series of 3,4-ethylenedioxythiophene derivatives carrying important pharamacophores, viz., amide, ester, ether and active secondary aryl moieties have been designed and synthesized through multistep reactions starting from thiodiglycolic ester and diethyl oxalate. They have been characterized by elemental and spectral data. All the target compounds have been screened for their anticonvulsant activity at three different models viz. maximal electroshock (MES), subcutaneous metrazole (scMET), and 6 Hz screen and evaluated for their neurotoxicity in rotorod model. Compound 6a emerged as lead with no neurotoxicity. All the five series of compounds are safe in the toxicity studies at the maximum dose of 300 mg/kg of body weight. Amongst the tested compounds, the ester pharmacophore with thioamide fragment has showed better activity than the other analogs.

• Journal of the Korea Institute of Military Science and Technology
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• v.16 no.2
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• pp.218-224
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• 2013

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.

• Bulletin of the Korean Chemical Society
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• v.26 no.11
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• pp.1757-1760
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• 2005

A series of 6-alkyloxyl-3,4-dihydro-2(1H)-quinoliones (5a-5n) were synthesized through nitration, reduction, diazotization, hydrolysis and alkylation from 3,4-dihydro-2(1H)-quinolione. Their structures were characterized by IR, $^1H$-NMR and MS. The anticonvulsant activity was evaluated by the Maximal electroshock test (MES) and the subcutaneous pentylenetetrazole (Metrazole) test (sc-Met). The neurotoxicity was measured by the Rotarod test (Tox). The result showed that 6-hexyloxy-3,4-dihydro-2 (1H)-quinolinone (5c) was potent in anti-MES and anti-scMet test with $ED_{50}$ of 24.0 mg/kg and 21.2 mg/kg, respectively, albeit its $TD_{50}$ (67.6 mg/kg) revealed the high neurotoxicity. 6-Benzyloxy-3,4-dihydro-2(1H)-quinolinone (5f) was less effective against MES induced seizure with $ED_{50}$ of 29.6 mg/kg, but no neurotoxicity was observed even under 300 mg/kg. Its Protective index (PI) was greater than 10 preferable to Phenytoin, Carbamazepin, Phenobarbital and Valproate.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.342-347
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• 2011

In the present study, the anticonvulsant effects of Artemisia capillaris Herba (AC) and its major constituent, esculetin (ECT), were tested and the mechanism studied. Locomotion, Myorelaxation, motor coordination and electroshock seizure experiment were conducted in mice. To identify the anticonvulsant mechanism effect of this drug, chemical-induced seizure in mice and the ionic movement in neuroblastoma cells were also observed. The ethanol extract of AC was orally administered to mice 30 min. prior to testing and ECT was intraperitoneally injected. AC and ECT treatment did not change locomotor activities as well as activities on the rota-rod, which indicates that they did not cause a sedative and myorelaxation effect. AC and ECT treatment increased threshold of convulsion induced by electroshock. AC treatment also inhibited convulsion induced by pentylenetetrazole. In the case of strychnine however, only high dose of AC treatment inhibited convulsion. AC and ECT treatment increased the $Cl^-$ influx into the intracellular area in a dose-dependent manner. On the other hand, bicuculline, a GABA antagonist, inhibited the $Cl^-$ influx induced by AC and ECT. These results indicate that ECT induces the anticonvulsive effect of AC extract through the GABAergic neuron.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1080-1085
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• 2006

A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.

• Journal of Korean Neurosurgical Society
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• v.29 no.12
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• pp.1673-1676
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• 2000

Anticonvulsant hypersensitivity syndrome is a rare but fatal complication. It manifests as fever, skin rash, lymphadenopathy, and hepatitis. Phenytoin, phenobarbital, and carbamazepine are the most frequently involved drugs. We here report a case of phenytoin-induced anticonvulsant hypersensitivity syndrome. A 37-year-old woman presented with fever and generalized skin rash, 3 weeks following commencement of phenytoin 400mg daily for treatment of seizure after superficial temporal artery-middle cerebral artery(STA-MCA) anastomosis for moyamoya disease. Her temperature was $39.3^{\circ}C$ and her face was edematous. Laboratory findings showed elevated hepatic enzymes and eosinophilia. Blood and urine culture were all negative. Initially, prednisolone was commenced at 30 mg daily. But fever and skin rash did not improved and hepatic function was more aggravated. After increasing dose of steroid(methylprednisolone 125mg/day), fever and skin rash disappeared and hepatic enzymes returned to normal range.

• Journal of Life Science
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• v.12 no.5
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• pp.505-514
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• 2002

The aim of this study was to evaluate the anticonvulsant activity of four agents derived from tropinone (T-1: 2,4-dipyrrolylmethenylnortropinone, T-2: 2,4-diphenylmethenylnortropinone, T-3 : 2,4-difurfurylmethenylnortropinone, T-4 : 2,4-dimethoxyphenylmethenylnortropinone) in NIH Swiss mouse. Pentylenetetrazole (nZ) was injected via intraperi-toniurn in mouse and Maximal Electroshock (MES) stimulation was through both conjunctivas by electrodes. Tropinone derivatives were treated at 15 minutes before PTZ or MES procedure. PIZ of 25 mg/kg induced generalized seizure in mouse, effects of tropinone derivatives on PTZ-induced seizure were monitored. Compared with control group, T-4 decreased seizure grade most effectively. Also T-4 increased onset time of PTZ-induced seizure. This result showed that T-4 is most effective on PTZ-induced seizure. In MES-induced seizure, T-1 decreased seizure grade and recovery time. nNOS expression in hippocampus and cortex were increased in nZ- and MES-induced seizure animals compared with control. Pretreatment of tropinone derivatives in PTZ-induced seizure did not affected nNOS expression in brain tissues, but T-1 and T-4 decreased nNOS expression in cortex of MES-induced seizure animals. These findings suggest that tropinone derivatives have specific anticonvulsant activities according to PTZ- and MES-induced seizure. 2,4- dimethoxyphenylmethenylnoroopinone is most effective in PTZ-induced seizure and 2,4-di methoxyphenylmethenylnortropinone is most effective in MES-induced seizure.

• Applied Biological Chemistry
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• v.43 no.1
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• pp.72-77
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• 2000

The repeated silica gel colum chromatographies of EtOAc fraction, showing anticonvulsant activity, obtained from MeOH extracts of Schizandra chinensis B. fruits led to isolation of a sesquiterpenoid, four lignans and a sterol glycoside. Their chemical structures were determined to be chamigrenal, gomisin A, gomisin H, gomisin N. schizandrin and daucosterol. Among them, schizandrin and daucosterol inhibited GABA degrative enzymes, succinic semialdehyde dehydrogenase and succinic semialdehyde reductase, respectively. It is postulated that the schizandrin and daucosterol are able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on GABA degrative enzymes and act as anticonvulsant drugs.