• Archives of Pharmacal Research
• /
• v.20 no.1
• /
• pp.53-57
• /
• 1997

For the purpose of defining the effects of the N-substituted alkyl groups on the anticonvulsant activities of N-Cbz-.alpha.-aminosuccinimides, various (R)- and (S)-N-alkyl substituted N-Cbz-.alpha.-aminosuccinimides (1 and 2) were prepared from the corresponding (R)- and (S)-N-Cbz-aspartic acid by using known reaction and were evaluated the anticonvulsant activies in the MES and PTZ tests, including their neurotoxicities. The most active compound in the MES test was (R)N-Cbz-.alpha.-amino-N-methylsuccinimide (1b) $(ED_{50}=52.5 mg/kg, Pl=3.2)$. And in case of the PTZ test, (R)-N-Cbz-.alpha.-amino-N-ethylsuccinimide (1c) was the most active compound $(ED_{50}/=32.5mg/kg, Pl=3.1)$. The order of anticonvulsant activities of these compounds against the MES test, as judged from the ED_50values for the R series (1), was N-methyl > N-isobutyl > non-substituted > N-ethyl, N-allyl > N-benzyl compound; for the S series (2) N-methyl > N-altyl > non-substituted > N-isobutyl > N-ethyl > N-benzyl compound. The anticonvulsant activities in the PTZ tests of these compounds exhibited somewhat different pattern ; for the R series (1) Nethyl > N-methyl > N-isobutyl> non-substituted > N-allyl > N-benzyl compound in order of decreasing activity; for S series (2) N-ethyl > N-allyl, non-substituted > N-isobutyl > N-methyl > N-benzyl compound in order of decreasing activity.

• YAKHAK HOEJI
• /
• v.54 no.1
• /
• pp.1-7
• /
• 2010

Valerian (Valeriana officinalis L.) is a perennial that has been used for medicinal purposes from the ancient times and valerian preparations including root and rhizome extracts are known to possess a variety of biological activities such as anticonvulsant, antidepressant, sleep aid, tranquilizer, and anti-HIV activities. Main components of the extracts were classified according to the structural features. Importantly, one of the main components, isovaleramide, has drawn our attention due to the concise structure, broad spectrum, and low toxicities. The general aspects including generation of this interesting molecule, a variety of activities, pharmacokinetic properties, derivatization, and fusion with other known drugs were described. Isovaleramide has been isolated from valerian probably as an isolation artifact after treatment of ammonia to prepare ammoniated tincture, and is known to exhibit anticonvulsant, anxiolytic, sedative, and sleep aid activities without distinct side effects such as excessive sedation and decreasing muscle tone. It was also found to be well absorbed into the circulation system without specific cytotoxicity and genotoxicity. The derivatives of isovaleramide, valpromide, valrocemide and valnoctamide were also briefly discussed.

• The Journal of Korean Medicine
• /
• v.25 no.1
• /
• pp.188-197
• /
• 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.

• Korean Journal of Pharmacognosy
• /
• v.27 no.1
• /
• pp.53-57
• /
• 1996

To elucidate the activities of Uncaria Ramulus et Uncus, which has been used as anticonvulsant and antihypertensive in oriental region, the methanolic extract and its fractions were applied to inhibition of convulsion onset. The ethyl acetate fraction showed dose-dependent inhibitory activity against pentylenetetrazole-induced seizure.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.2
• /
• pp.447-452
• /
• 2010

A series of 5-alkoxy-tetrazolo[1,5-a]quinolines were synthesized to evaluate their anticonvulsant and antidepressant effects. Anticonvulsant effects and neurotoxicity of the compounds when injected intraperitoneally to mice were determined by a maximal electroshock (MES) test and a rotarod test, respectively. Only three of the synthesized compounds (4a, 4b, 4c) displayed anticonvulsant activity at a dose of 300 mg/kg. Most of the compounds significantly reduced immobility times during the forced swimming test (FST) at a dose of 100 mg/kg, indicative of antidepressant activity. Among the compounds, 5-(2-fluorobenzyloxy)tetrazolo[1,5-a]quinoline (4k) reduced immobility time by 66.85% at 30 mg/kg compared with the same dose of Fluoxetine, which reduced immobility time by 52.30%. According to the results of the 5-Hydroxytryptophan induced head-twitch test and yohimbine toxicity potentiation test, the noradrenergic system seems not to be involved in the antidepressant-like effect of compound 4k while the serotonergic system seems a little to be involved.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.1
• /
• pp.206-213
• /
• 2004

This study was performed to evaluate the anticonvulsant, antioxidant effect of modified formulas Korean traditional medicine Gungchihwadam-Jeon(GCHDJ). The extract of GCHDJ was administered (p.o.) to mice for 14 days in anticonvulsant and antioxidant tests. The pretreatment of GCHDJ extract prohibited the pentylenetrazol(PTZ)-induced convulsion in PTZ-induced convulsion, lowered level of brain r-aminobutyric acid(GABA) was restored by the pretreatment of GCHDJ. Increased level of brain glutamic acid was lowered to normal state by GCHDJ, and increased activity of brain r-aminobutyric acid transaminase(GABA-T) was reduced by GCHDJ. In PTZ-induced convulsion, increased level of brain lipid peroxide was lowered to normal state by the pretreatment of GCHDJ. Increased activity of brain xanthine oxidase(XOD) was lowered to normal state by GCHDJ, and increased activity of brain aldehyde oxidase lowered to normal state by GCHDJ. In PTZ-induced convulsion, increased activities of superoxide dismutase(SOD) and catalase in brain were lowered by the pretreatment of GCHDJ, whereas increased level of glutathione and increased activity of gluthathione peroxidase in brain were not changed significantly. Above results suggest that GCHDJ have 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, GCHDJ could be applied to various convulsive disorders.

• Archives of Pharmacal Research
• /
• v.23 no.4
• /
• pp.344-348
• /
• 2000

80% Aqueous MeOH extracts from the wood of Caesalpinia sappan, which showed remarkable anticonvulsant activity, were fractionated using EtOAc, n-BuOH, and $H_2$O. Among them, the EtOAc fraction significantly inhibited the activities of two GABA degradative enzymes, succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR). Repeated column chromatographies for the fraction guided by activity test led to the isolation of the two active principal components. Their chemical structures were determined to be sappanchalcone and brazilin based on spectral data. The pure compounds, sappanchalcone (1) and brazilin (2), inactivated the SSAR activities in a dose dependent manner, whereas SSADH was inhibited partially by sappanchalcone and not by brazilin.

• Korean Journal of Pharmacognosy
• /
• v.29 no.3
• /
• pp.187-192
• /
• 1998

The ethyl acetate fraction of Uncariae Ramulus et Uncus, which showed anticonvulsant effects against pentylenetetrazole (PTZ) treated mice, were subjected to column chromatography to isolate ursolic acid and hyperin from active eluate. Hyperin decreased the elevated activities of GABA-T and xanthine oxidase and lipid peroxide level dose-dependently in PTZ treated mice brain tissue in vitro, but no effect on superoxide dismutase activity. The effects on such enzyme and component seemed to be related with biosynthesis or metabolism of neurotransmitters.

• Archives of Pharmacal Research
• /
• v.19 no.4
• /
• pp.312-316
• /
• 1996

A series of N-Cbz${alpha}$-aminosucinimides (1), combining common moieties of various anticonvulsants such as N-CO-C-N and cyclic imide in a single molecule, were synthesized from the corresponding (R)- and (S)-N-Cbz-aspartic acid (2). And their in vivo anticonvulsant evaluations in MES and PTZ test were investigated. And also the rotorod test for neurotoxicity was investigated. All the tested compounds (1), except 1c and 1f, showed significant anticonvulsant activities in both MES and PTZ test. And the most active compound among them in MES test was (R)-N-Cbz-${alpha}$-amino-N-methylsuccinimide (1b) $(ED_50/=52.5 mg/kg)$ and (S)-N-Cbz-aminosuccinimide((1d) was most active in PTZ test $(ED_50/=78.1 mg/kg)$. And the $TD_50$ values of the tested compounds were above 117.5 mg/kg. These pharmacological data were comparable to those of currently available anticonvulsants. And also we found that the pharmacological effects were dependent on their N-substituted alkyl chains and their stereochemistry.

• Korean Journal of Pharmacognosy
• /
• v.30 no.3
• /
• pp.284-289
• /
• 1999

In order to find active ingradients having an agonistic activity to benzodiazepine receptor from Gastrodia elata Blume (Orchidaceae) which has been used as an anticonvulsant in oriental medicine, one component and some fractions were separated from the butanol extract of the rhizomes of this plant and evaluated for their activities on GABA/benzodiazepine receptor in vitro. As a result, one crude mixture (F4f) obtained from the most active fraction (F4) inhibited significantly the binding of $[^3H]Ro15-1788$, a selective benzodiazepine receptor antagonist, to benzodiazepine receptor of rat cortices. GABA significantly enhanced the inhibition of $[^3H]flunitrazepam$ binding by F4f, and this positive GABA shift supported the strong possibility of the agonistic activity of F4f to benzodiazepine receptor.