• Biomolecules & Therapeutics
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• 제1권1호
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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.

• 생약학회지
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• 제29권3호
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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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• 제31권11호
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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.

• 한국군사과학기술학회지
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• 제16권2호
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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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• 제26권11호
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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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• 제19권3호
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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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• 제29권12호
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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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• 제29권12호
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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.

• 생명과학회지
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• 제12권5호
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• pp.505-514
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• 2002

생쥐에서 최근 합성된 4가지 종류의 tropinone유도체들의 항경련 효과를 조사하기 위하여 pentylenetetrazole (PTZ) 및 Maximal Electroshock (MES)로 유발된 경련에 tropinone 유도체들이 경련상태에 미치는 효과를 관찰하였다. Troponine 유도체로는 화학구조가 다른 4가지 종류를 사용하였다(T-1:2,4-dipywolylmethenylnortropinone, T-2:2,L di phenylme thenylnortropinone, T-3 : 2,Ldifurfurylmetheny- Inortropinone, 74 : 2,4-dimetho xyphenylmethenylnortro- pinone). nZ 25 mg/kg을 복강 내로 투여 후 전신성 경련을 유발하였으며 tropinone 유도체를 전처치한 후 PTZ에 의한 경련의 변화를 관찰하였다. 대조군에 비하여 T-1과 T-2는 경련정도에 변화가 없었으나 T-3과 T-4는 유의하게 경련정도를 약화시켰다. PTZ에 의한 경련의 시작 시간은 T-4에서 유의하게 지연되어 T-4가 PTZ에 의한 경련에 항경련 효과가 있음을 나타내었다. MES로 경련을 유발한 경우에 있어서는 T-1이 경련정도를 유의하게 약화시켰으며 경련 후 회복시간도 T-1에서 가장 빨리 회복되는 특성을 보였다. 따라서 T-1이 MES에 의한 경련유발에 항경련 효과가 있음을 나타내었다. Troponine 유도체에 의한 경련 억제 효과와 경련과 동반되어 증가한다고 알려진 neuronal nitric oxide synthase (nNOS) 발현과의 관계를 알아보기 위하여 조직 단백질에서 Western blot을 하였다. 대조군에 비하여 PTZ 및 MES에 의해 경련을 유발한 생쥐에서 모두 해마부 및 전뇌피질부에서 nNOS가 증가하였다. Tropinone 유도체를 투여하지 않고 경련을 유발시킨 대조군에 비하여 tropinone 유도체를 투여한 군에서도 모두 nNOS의 발현이 해마부 및 전뇌피질부에서 증가되었다. MES로 경련을 유발한 생쥐에서 대조군에 비하여 T-1 및 T-4는 피질부에서 nNOS가 감소했으나 나머지군에서는 감소가 없었다. 이 상의 결과를 토대로 tropinone 유도체들은 경련유발의 자극 조건에 따라 항경련 효과가 다르게 나타났으며, PTZ유 발경련에서 2,4-dimethoxyphenylmethenylnortropinone의 항경련 효과가 가장 크고, MES 유발경련에서는 2,4-dipyrrolylmethenylnortropinone의 항경련 효과가 가장 크게 나타났다.

• Applied Biological Chemistry
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• 제43권1호
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• pp.72-77
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• 2000

항경련 활성을 보인 오미자의 열매로부터 활성물질을 분리하기 위하여 MeOH로 추출하고, 추출물을 EtOAc, n-BuOH 및 물로 분배, 추출하였다. 얻어진 각 분획에 대하여 중추 신경계에서 억제성 신경전달물질로 알려진 ${\gamma}-aminobutyric$ acid(GABA)의 대사조절효소들인 succinic semialdehyde reductase (SSAR) 및 succinic semi-aldehyde dehydrogenase(SSADH)의 활성을 측정하였다. 활성 억제효과를 나타낸 EtOAc 분획으로부터 silica gel column comatography를 반복하여 sesquiterpene 및 sterol 배당체 각 1종, lignan화합물 4종을 분리, 정제하였다. 각각의 화학구조는 NMR, MS 등의 스펙트럼 데이터를 해석하여, chamigrenal, daucosterol, gomisin A, gomisin H, gomisin N 및 schizandrin으로 동정하였다. 각 화합물에 대하여 활성을 측정한 결과, schizandrin을 SSADH와 1시간 전처리하였을 때 효소의 활성은 65% 억제되었으며, daucosterol의 경우에는 같은 조건에서 SSAR의 활성을 80% 억제하는 것을 관찰할 수 있었다.