• Bulletin of the Korean Chemical Society
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• v.26 no.11
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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.

• Archives of Pharmacal Research
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• v.29 no.12
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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 Oriental Neuropsychiatry
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• v.13 no.2
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• pp.195-211
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• 2002

Gagamguibitang, a composite Korean medicinal drug prescribed by us, was evaluated for its sedative effects by measurements of potentiation on pentobarbital-induced sleeping time, anticonvulsive activities in animal model, inhibitory effect on GABA transaminase activity, and antioxidative activities in vitro- and/or in vivo assay. The results were summerized as follows : 1. Gagamguibitang showed about 2-fold prolongation of pentobarbital-induced sleeping time compared to the control group after administration(p.o) with 2.0g/kg of mice body weight. 2. Gagamguibitang strongly lengthened onset time of pentylenetetrazole-induced convulsion, shortened the duration of convulsion and diminished the lethality after treatment(p.o) with 1.0g/kg of mice body weight. 3. Gagamguibitang inhibited dose-dependently the brain GABA transaminase activity in vitro compared to the control group and in vivo compared to the pentylenetetrazole-treated group. 4. Gagamguibitang inhibited effectively brain lipid peroxidation by 45.8% at a dose of l0mg/ml in vitro and by 47.5% after oral treatment with 0.5g/kg of mice body weight in vivo assay. 5. Gagamguibitang exhibited a potent scavenging activity on DPPH radical in a dose-dependent manner with ca. 92% activity at l0mg/ml. As a result, Gagamguibitang can be useful for the effective sedative drug in clinical application.

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2733-2737
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• 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.

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.63-68
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• 2001

General pharmacological properties of (R)-JG-381 were examined in laboratory animals to investigate its safety profile. Administration of (R)-JG-381 (50 and 100 mg/kg) in mice and rats had no effects of general behaviors, central nervous system of the animals in test systems of pentobarbital-induced sleeping time, writhing syndromes induced by 0.7% acetic acid, chemo-shock produced by pentylenetetrazole, and, however, had mild effects on motor coordination. Heart rate and blood pressure were not changed by (R)-JG-381 treatment. (R)-JG-381 also showed mild effects on intestinal propulsion and gastric secretion. These results suggest that (R)-JG-381 dose not exert serious pharmacological effects.

• Toxicological Research
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• v.8 no.1
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• pp.63-70
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• 1992

The present study was performed to evaluate whether the application of Fenbufen is reasonable for predicting the convulsive liability of the quinolone derivatives and to examine whether pentylenetetrazole (PTZ) can be used as a screening tool for their Central Nervous System (CNS) toxic pontential. The convulsive activity of the quinolones was markedly potentiated by the pretreatment of Fenbufen. In combination with Fenbufen, enoxacin (ENX), norfloxacin (XFLX), and ciprofloxacin (CPFX) provoked convlusions and subsequent death at the intravenous doses of 0.5mg/kg, 10mg/kg, and 40mg/kg, respectively, whereas ofloxacin (OFLX) and pefloxacin (PFLX) did not induce convulsions and death even at a relatively high dose of 100mg/kg iv.

• The Journal of Internal Korean Medicine
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• v.21 no.5
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• pp.781-789
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• 2000

Objective : The purpose of these research was to investigate effects of water extract of Bistortae Rhizoma(BRE) on the hemostasia, anti-inflammatory action and central nervous system. Methods : we used mice and rats administered with the extract of the above herbs. Results : BRE decreased the permeability of evans blue into peritoneal cavity and cotton pellet granuloma formation. BRE did not decrease the acetic acid induced writhing syndrome and the histamine induced mouse paw edema. BRE inhibited the pentylenetetrazole and the strychnine induced convulsion. BRE shortened the bleeding time and plasma prtrombin time. BRE did not affect on the proliferation of Balb/c 3T3 cells. Conclusions : these results suggest that the effects of BRE are the hemostasia, anti-inflammatory action, and mild depressant activity of central nervous system.

• 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.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.273.2-274
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• 2003

The present study was designed to evaluate central inhibitory effects of an essential oil from Acori graminei Rhizoma (AGR), the dry rhizomes of Acorus gramineus Solander (Araceae) upon fragrance inhalation (aroma therapy). Preinhalation of an essential oil of AGR markedly delayed the appearance of pentylenetetrazole-induced convulsion. Furthermore, the inhalation of an essential oil of AGR impressively inhibited the activity of ${\gamma}$-aminobutyric acid (GABA) transaminase, a degradating enzyme for GABA as inhalation period is lengthened. (omitted)

• Korean Journal of Pharmacognosy
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• v.29 no.3
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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.