• Archives of Pharmacal Research
• /
• 제20권1호
• /
• 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.

• Archives of Pharmacal Research
• /
• 제22권5호
• /
• pp.491-495
• /
• 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.

• Tuberculosis and Respiratory Diseases
• /
• 제57권1호
• /
• pp.55-60
• /
• 2004

간질이나 신경성 통증 등으로 많이 쓰이고 있는 phenytoin, carbamazepine, 그리고 phenobarbital등의 항경련제는 피부, 임파절, 간 그리고 폐 등을 포함하는 전신적인 반응을 동반하는 anticonvulsant hyper-sensitivity syndrome을 유발할 수 있다. 그 임상양상은 환자에 따라 매우 다양하며 드물게 치명적인 경과를 가질 수 있어 의심되는 경우에는 약제의 사용중단이 가장 중요한 것으로 알려져 있다. 저자들은 carbamazepine을 투여 후 피부병변, 고열, 호산구증다증, 임파절종대와 호산구성폐렴을 보였던 환자를 anticonvulsant hypersensitivity syndorme으로 진단하고 원인약제 투여중단 후, 증상, 혈액학적 이상소견 그리고 방사선학적 이상소견의 호전이 관찰되었던 1예을 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• Archives of Pharmacal Research
• /
• 제19권4호
• /
• 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.

• 대한화학회지
• /
• 제64권1호
• /
• pp.7-18
• /
• 2020

An efficient and facile procedure has been developed for the synthesis of novel bichalcone derivatives (4a, 4b). The key step contains the solvent-free aldol synthesis of bichalcones based on quinones. Bichalcones (4a, 4b) were used as precursors for the synthesis of some interesting heterocyclic compounds like, diazepines (5a, 5b), pyrazolo-pyrimidines (7a, 7b), and pyrazoline derivatives (8a, 8b). Moreover, new thioxopyrimidine derivatives (9a, 9b) were furnished and used as a functionalizing agent to produce the triazole-pyrimidines (11, 12) and the carbonitrile derivative (14). All the synthesized compounds were fully characterized using physical and spectral data like, FT-IR, ¹H NMR, ¹³C NMR, and MS. Bichalcones (4a, 4b) and diazepines (5a, 5b) were screened for their anticonvulsant activity, where compounds (4a, 5a, and 5b) revealed potent anticonvulsant activity compared to diazepam. On the other hand, some of the prepared compounds were screened for their antiproliferative activity and they showed significant cytotoxic effects on most of the cancer cell lines with regard to broad spectrum antitumor activity.

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

• 동의신경정신과학회지
• /
• 제18권3호
• /
• pp.83-95
• /
• 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.

• 동의생리병리학회지
• /
• 제18권1호
• /
• 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.

• Bulletin of the Korean Chemical Society
• /
• 제35권9호
• /
• pp.2733-2737
• /
• 2014

A series of pyrazolyl thiosemicarbazone derivatives were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. Interestingly, all compounds prepared showed long duration of protection effect in the MES screens. Among them, compound 5b was considered as the most promising one with an $ED_{50}$ value of 47.3 mg/kg, and a PI value of 4.8, which was superior to phenobarbital and valproate in the aspect of safety. Furthermore, compound 5b showed protection against seizures induced by pentylenetetrazole suggesting that compound 5b may exert anticonvulsant activity through GABA-mediated mechanisms.

• Neonatal Medicine
• /
• 제16권1호
• /
• pp.10-17
• /
• 2009

The immature neonatal brain is susceptible to the development of seizures. Seizures occur in 1% to 5% of infants during the neonatal period. Neonatal seizures are most commonly associated with serious acute illnesses, such as hypoxic-ischemic encephalopathy, birth trauma, metabolic disturbances, or infections. Thus, newborn infants with seizures are at risk for neonatal death and survivors are at risk for neurologic impairment, developmental delay, and subsequent epilepsy. Experimental data have also raised concerns about the potential adverse effects of the currently used anticonvulsants in neonates on brain development. Therefore, in the management of neonatal seizures, confirmatory diagnosis and optimal, but shorter, duration of anticonvulsant therapy is essential. Nevertheless, there has been substantial progress in understanding the developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. The currently used therapies have limited efficacy and the treatment of neonatal seizures has not significantly changed in the past several decades, This review includes an overview of current approaches to the treatment of neonatal seizures.