• Archives of Pharmacal Research
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• 제29권6호
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• pp.459-463
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• 2006

Previous studies on the anticonvulsant activity of $N-Cbz-{\alpha}-aminoglutarmides$ have shown that the derivatives of $N-Cbz-{\alpha}-amino-N-alkoxy$ glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of $N-Cbz-{\alpha}-amino-glutarimidooxy$ carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of $N-Cbz-{\alpha}-amino-glutarimidooxy$ acetic acid 3a $(ED_{50}\;=\;42.9\;mg/kg)$.

• Archives of Pharmacal Research
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• 제19권3호
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• pp.248-250
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• 1996

In conclusion, a series of N-Cbz-.alpha.-amono-glutarimides (1a-f), combining common structures such as N-CO-C-N and cyclic imide in a single molecule, were prepared from the (R)- or (S)-N-Cbz-glutamic acid and evaluated for their anticonvulsant activities in MES and PTZ tests in order to develope new and broad spectrum anticonvulsant. In this study, N-Cbz-.alpha.-aminoglutarimides (1) except ac and af, showed significant anticonvulsant activity in both MES and PTZ tests enough to be recommended as promising new anticonvulsant drug candidates. Now we are continuing to investigate further anticonvulsant test (quantification)for these compounds and synthesize their analogues in order to develop more active anticonvulsant and define the structure activity relationship more precisely.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.495-501
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• 2004

A series of N-substituted-1,3-isoindolinedione derivatives (2-16) were synthesized for the purpose of defining the effect of N-substitution on the anticonvulsant activity of these derivatives. The target compounds (2-16) were obtained by condensation of phthalic anhydride with the corresponding amine derivative. The structures of the synthesized derivatives (2-16) were confirmed by means of IR, $^1$H-NMR, $^{13}$ C-NMR, MS and elemental analyses. The anticonvulsant activity of all compounds (2-16) were evaluated by subcutaneous pentylenetetrazole seizure threshold test at doses of 0.2, 0.4 and 0.8 mmol/kg compared with sodium valproate as a positive control. Their neurotoxicity were determined by the rotorod test. Many of the present series of compounds showed good anticonvulsant activity at the tested doses, as compared to sodium valproate. Three of them (4, 6 and 11) exhibited 100 % protection against convulsions, neurotoxicity and death at all tested doses. Out of the series, two compounds (12 and 13) were completely inactive with 100% mortality. 3-(p-chlorophenyl)-4-(1 ,3-dioxo-2,3-dihydro-1 H-2-isoindolyl) butanoic acid derivative (11) has emerged as the most active compound which is 20 times more active than valproate with ED$_{50}$ 8.7, 169 mg/kg; TD$_{50}$ 413, 406 mg/kg and PI 47.5, 2.4. The results revealed the importance of the combination of baclofenic and phthalimide moieties (compound 11) as a promising anticonvulsant candidate.

• 대한한의학회지
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• 제25권1호
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• pp.188-197
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• 2004

Objective and Methods : This study was performed to evaluate the anticonvulsant, antioxidant effect of modified formulas Korean traditional medicine Cheongsinhwadam-Jeon(CSHDJ). The extract of CSHDJ was administered (p.o.) to mice for 14 days in anticonvulsant and antioxidant tests. Results : The pretreatment of CSHDJ extract prohibited pentylenetrazol (PTZ)-induced convulsion. In PTZ-induced convulsion, lowered level of brain ${\gamma}$-aminobutyric acid(GABA) was restored normal state by the pretreatment of CSHDJ. Increased level of brain glutamic acid was lowered to normal state by CSHDJ, and increased activity of brain ${\gamma}-aminobutyric$ acid transaminase(GABA-T) was reduced to normal state by CSHDJ. In PTZ-induced convulsion, increased level of brain lipid peroxide was lowered to normal state by the pretreatment of CSHDJ. Increased activity of brain xanthine oxidase(XOD) was lowered by CSHDJ, and increased activity of brain aldehyde oxidase lowered to normal state by CSHDJ. In PTZ-induced convulsion, increased activities of superoxide dismutase(SOD) and catalase in brain were lowered by the pretreatment of CSHDJ, whereas increased level of glutathione and increased activity of gluthathione peroxidase in brain were not changed significantly. Conclusions : Above results suggest that CSHDJ has anticonvulsant, antioxidant effect. That seems to be strongly related with the levels of GABA, glutamate, lipid peroxide and the activities of GABA-T, XOD, aldehyde oxidase, SOD, catalase in brain tissue. From these results, CSHDJ could be applied to various convulsive disorders.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.535-540
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• 2006

Several novel 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzo[d][1,2,3]triazoles (3a-h) have been synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) and appropriate acid chlorides. 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) was synthesized by reacting 3-(1H-benzo[d][1,2,3]triazol-1-yl)propanenitrile with sodium azide and ammonium chloride in the presence of dimethylformamide. The synthesized compounds were characterized by IR and PMR analysis. The titled compounds were evaluated for their in vitro antibacterial and antifungal activity by the cup plate method and anticonvulsant activity evaluated by the maximal electroshock induced convulsion method in mice. All synthesized compounds exhibited moderate antibacterial activity against Bacillus subtilis and moderate antifungal activity against Candida albicans. Compounds 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4-aminophenyl)methanone 3d and 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(2-aminophenyl)methanone 3e elicited excellent anticonvulsant activity.

• 약학회지
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• 제45권1호
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• pp.7-15
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• 2001

For the purpose of defining the effects of N-acyl groups on the anticonvulsant activities of N-acyl-$\alpha$-amino-glutarimides, various (R)- and (S)-N-acyl-$\alpha$-aminoglutarimide were prepared from the corresponding N-Cbz-glutamic acid and were evaluated their anticonvulsant activities in the MES and PTZ test, including their neurotoxicities. Among the tested compounds, only (R) N-cinnamoyl-$\alpha$-amino-N-methylglutarimide showed anticonvulsant activity in the MES and PTZ test. And the other tested compounds was active in the only PTZ test. The order of anticonvulsant activities in the PTZ test was as followes; for the (R) series, N-4-methoxycinnamoyl = cinnamoyl > N-4-nitrobenzoyl > N-benzoyl > N-phenylacetyl; for the (S) series, N-4-methoxycinnamoyl = N-3-nitrobenzoyl > N-4-nitrobenzoyl = N-cinnamoyl = N-phenylacetyl. From the above results, it was conceivable that the substituted N-acyl group had important effects on the anticonvulsant activities of these compounds. However stereoisomeric deferences in the anticonvulsant activities were not exhibited clearly.

• Advances in Traditional Medicine
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• 제7권1호
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• pp.46-50
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• 2007

Callus cultures of Convolvulus microphyllus Sieb. was induced on Murashige and Skoog's medium supplemented with 2,4-dichloro phenoxy acetic acid, 6-benzyl adenine, indole acetic acid and kinetin (1 ppm each). Methanolic extracts of whole plant, leaf, stem and leaf and stem calli were tested for anticonvulsant activity against standard drug phenytoin using maximal electroshock model on mice. It was observed that the animals treated with methanolic extracts of stem callus, leaf callus and whole plant (200 mg/kg, oral) showed significant protection against tonic convulsions induced by transcorneal electroshock. Anticonvulsant activity of methanolic extract of stem callus was comparable to that of standard drug phenytoin.

• 약학회지
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• 제32권1호
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• pp.40-49
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• 1988

There is evidence that brain norepinephrine may play a role in experimentally induced seizures in animals. Thus the present experiments were undertaken in an attempt to explore the role of brain norepinephrine in anticonvulsant activity of clonazepam. 6-Hydroxydopamine was given to newborn rats and PTZ-induced seizures were tested $70{\sim}90$ days after birth and the rats were killed for determination of brain norepinephrine 8 days after the seizure test. Depletion of norepinephrine in the rat brain significantly potentiated the PTZ-induced convulsions and antagonized the effect of clonazepam on clonic seizures, tonic seizures and the number of seizures, but the latency to the seizure and the mortality has not been altered. However the 6-hydroxydopamine-induced antagonism of anticonvulsant action was surmountable by increasing the dose of clonazepam. These results show that brain norepinephrine may play an important role in seizure susceptability as well as in the anticonvulsant activity of clonazepam in rats.

• Bulletin of the Korean Chemical Society
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• 제32권3호
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• pp.1011-1016
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• 2011

A series of thiadiazole derivatives were synthesized with differently substituted benzoic acids which were cyclized to give differently substituted thiazolidin-4-one. Elemental analysis, IR, $^1H$ NMR, $^{13}C$ NMR and mass spectral data confirmed the structure of the synthesized compounds. The derivatives of these moieties were evaluated for anticonvulsant activity by MES model and neurotoxicity by rotarod method. The synthesized compounds showed good potential for anticonvulsant activity besides this, the compounds also showed neurotoxic effect. It was observed that compounds with $OCH_3$ at 3, 4 position of phenyl ring [5(a-l)] showed less protection against convulsions as compared to compounds having unsubstituted phenyl ring [4(a-l)].

• 생약학회지
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• 제23권1호
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• pp.34-42
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• 1992

The analgesic, anticonvulsant and anti-inflammatory actives of leaves of Hedera rhombea Bean were evaluated. The methanol and butanol fractions showed considerable analgesic activity, but no anticonvulsant activities. Anti-inflammatory activity was found in the methanol, butanol and ether fractions by carrageenin induced edema test.