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

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1194-1201
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• 2004

Michael addition of certain nucleophiles on ${\alpha}$ , ${\beta}$-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with ${\alpha}$-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17. Selected compounds (13 and 6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds 13a and 13c offered the highest anticonvulsant activity. Meanwhile compound 13c showed the highest potentiation of phenobarbital induced sleep in mice.

• Journal of Oriental Neuropsychiatry
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• v.18 no.3
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• pp.83-95
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• 2007

This study was performed to examine the anticonvulsant effects of the extracts of JeongGan-Tang and explanation of its action mechanism. Method: 1) The inhibitory effect on convulsions induced by pentylenetetrazole, picrotoxin and strychnine was investigated in vivo 2) The inhibitory effect on GABA transaminase activity was evaluated in vivo and in vitro. 3) The brain GABA level and glutamate level in pentylenetetrazole-induced convulsion model were analyzed by HPLC, Results: 1) JeongGan-Tang showed the significant effect on the pentylenetetrazole-induced convulsion, which may mean that its anticonvulsant effect would be resulted from the activation of GABA receptor and chloride channel rather than the presynaptic- or postsynaptic inhibition. 2) JeongGan-Tang exhibited proper inhibitory activity on GABA transaminase in vitro and in vivo. 3) JeongGan-Tang increased the brain GABA level but did not affect the brain glutamate content, which may suggest that this drug supresses the convulsion by increase of GABA, an inhibitory neurotransmitter. Conclusion : JeongGan-Tang can be used as an anticonvulsant prescription by the modulation of GABAergic neurotramission.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.491-495
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• 1999

In order to examine the effects of N-substituted alkyl group on the anticonvulsant activities of N-Cbz-$\alpha$-aminoglutarimides as novel anticonvulsants with broad spectrum, a series of (R) or (S) N-Cbz-$\alpha$-amino-N-alkylglutarimides (1 and 2) were prepared from the corresponding (R) or (S) N-Cbz-glutamic acid and evaluated for the anticonvulsant activities in the maximal electroshock seizure (MES) test and pentylenetetrazol induced seizure(PTZ) test, including the neurotoxicity. The most potent compound in the MES test was (S) N-Cbz-$\alpha$-amino-N-methylglutarimide($ED_{50}$=36.3 mg/kg, PI=1.7). This compound was also most potent in the PTZ test ($ED_{50}$=12.5 mg/kg, PI=5.0). The order of anticonvulsant activities against the MES test as evaluated form $ED_{50}$ values for (R) series was N-methyl > N-H > N-ethyl > N-allyl ; for the (S) series N-methyl > N-H > N-ethyl > N-alkyl > N-isobutyl compound. Against the PTZ tests, the order of anticonvulsant activities showed similar pattern ; for the (R) series, N-methyl > N-H > N-ethyl > N-allyl ; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. From the above results, N-substituted alkyl groups were though to play an important role for the anticonvulsant activities of N-Cbz-$\alpha$-amino-N-alkylgutarimides.

• YAKHAK HOEJI
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• v.31 no.1
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• pp.19-24
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• 1987

In order to find out the pharmacologically active but less toxic compounds than piperine, the actions of several amide derivatives of 5-phenyl-2, 4-pentadienoic acid on the CNS depressant activities were examined. The nine amide derivatives were investigated by using ICR mice as an experimental amimals on acute toxicities, anticonvulsant, sedative, analgesic and antipyretic effects. In the case of acute toxicities, all derivatives were weaker than piperine except compound III. Compound I showed strong anticonvulsant activity. On the other hand, compound I, III and IV significantly prolonged the sleeping time induced by hexobarbital in mice. Compound I, III and IV exhibited better analgesic effect than aspirin while compound II, V, VII and IX showed similar antipyretic activity to aspirin.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.344-348
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• 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
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• v.29 no.3
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• pp.187-192
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• 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
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• v.19 no.4
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• pp.312-316
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• 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.

• Journal of Hospice and Palliative Care
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• v.1 no.1
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• pp.65-68
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• 1998

The neuropathic pains are not well controlled by common analgesics and opioid drugs in terminal cancer patients. The types of these pains are divided within the two cages, one is due to continuous central sensitization and the other is due to paroxymal peripheral sensitization. The mechanism of continuous central sensitization is the activity of dorsal horn neurones that are activated by C-fiber input. The tricyclic antidepressants, non-tricyclic antidepressants, and oral local anaesthesia probably produce analgesic effects in neuropathic pains through suppression of this activity. The mechanism of paroxymal peripheral sensitization is the hyper-excitability of peripheral neurones. The neuropathic pains due to peripheral sensitization respond relatively the anticonvulsants and baclofen that stabilize membranes and suppress paroxymal electrical discharge. The patients was a 38-year-old female who complained of hyperthemia on upper right extremity. The symptom of this patient was improved with anticonvulsant(dilantin 600mg).

• 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.