• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.184-189
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• 1996

General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304 following oral administration of 300 mg/kg and 1000 mg/kg, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 mg/kg, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 mg/kg, LB20304a showed some analgesic effects in mice, and oral dose of 1000 mg/kg caused drop in normal body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of unto 300 mg/kg. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 mg/kg and 300 mg/kg, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 mg/kg and 200 mg/kg, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 mg/kg, and increased intestinal motility of mice at dose of 300 mg/kg. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 mg/kg of LB 20304a.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.173-184
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• 1994

The general and some pharmacological actions of DWP 305 were investigated in animals and the following results were obtained. In central nervous system, DWP 305 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in mice and body temperature in rat. DWP 305 showed no depressive action on convulsion induced by strychnine, electronic shock and pentylenetetrazole. From these results, DWP 305 was considered to have no pharmacological effect on the central nervous system. Furthermore, DWP 305 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 305 inhibited contractive effects against the acetylcholine (10$^{-6}$ g/mι), histamine (10$^{-6}$ g/mι), 5-hydroxytryptamine (10$^{-6}$ g/mι) and BaCl$_2$(10$^{-4}$ g/mι) at a concentration of 2.15$\times$10$^{-4}$ g/ml in bath. In the isolated trachea and vats deference, DWP 305 showed no effect on the contractions produced by histamine and norepinephrine, respectively. DWP 305 showed inhibitory effect on the contractions produced by acetylcholine and oxytocin at a concentration of 2.15$\times$10$^{-4}$ g/ml on the isolated nonpregnant rat uterus. DWP 305 had no effect on the isolated right atrium of guinea pig, bile excretion, urine volume, pH, gastrointestinal motility, gastric secretion and blood aggregation.

• YAKHAK HOEJI
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• v.38 no.5
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• pp.586-594
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• 1994

The general pharmacological effects of DWQ-013, a new synthetic quinolone antibacterial agent, were examined on the central nervous system in experimentral animals and the following results were obtained. Drug interaction of DWQ-013 with theophylline, fenbufen and nonsteroidal antiinflammatory drugs was also examined. DWQ-013 decreased touch escape effect on the general behavior and decreased body temperature at a concentration of 1000 mg/kg in mice. But DWQ 013 had no effect on the locomotor activity, rotarod perfomance and traction test in mice. Furthermore, DWQ-013 increased pentobarbital-induced sleeping time and affected the onset time in acetic acid-induced writhing test in mice. DWQ-013 reduced onset time and death time on strychnine-induced convulsions and death time on pentylenetetrazole-induced convulsions at a concentration of 1000 mg/kg in mice. But, the drug had no effect on the electroshock. DWQ-013 did not interact with fenbufen and any other NSAIDs but it did interact with theophylline. From these results, it could be suggested that DWQ-013 had less pharmacological effect than other quinolones on the central nervous system.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.764-768
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• 1998

In connection with the development of new anticonvulsant agents with a broad spectrum, we reported that N-Cbz-alpha-aminoglutarimides, combining common structures of othe r anticonvulsants such as N-CO-C-N and cyclic imides in a single molecule, showed significant anticonvulsant activities in the MES (maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure) tests. In these studies, a series of (R) and (S) N-alkyloxycarbonyl-alpha-aminoglutarimides 7a-7e and 8a-8e, which were substituted with various alkyloxycarbonyl group instead of Cbz group, were prepared from the corresponding (R) and (S) N-Cbz-glutamic acid 3 and 4, and were evaluated with their anticonvulsant activities against the MES and PTZ tests, including neurotoxicity, in order to define the effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-${\alpha}$-aminoglutarimides. Among them, (S)N-4-nitrobenzyloxycarbonyl-${\alpha}$-amino-N-methylglutarimide 8e was the most active in MES ($ED_{50}$=35.6mg/kg, PI=2.7) and PTZ tests ($ED_{50}$=15.6, PI=6.1). Interestingly, (R) and (S) N-4-nitrobenzyloxycarbonyl-${\alpha}$-amino-N-methylglutarimide 7e and 8e and (R) N-phenoxycarbonyl-${\alpha}$-amino-N-methylglutrimide 7d showed significant anti-convulsant activities in both the MES and PTZ tests and other compounds showed anticonvulsant activities in only the PTZ test. In addition, it was found that their anticonvulsant activities were dependent on their stereochemistries and N-substituted alkyloxycarbonyl groups.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.342-347
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• 2011

In the present study, the anticonvulsant effects of Artemisia capillaris Herba (AC) and its major constituent, esculetin (ECT), were tested and the mechanism studied. Locomotion, Myorelaxation, motor coordination and electroshock seizure experiment were conducted in mice. To identify the anticonvulsant mechanism effect of this drug, chemical-induced seizure in mice and the ionic movement in neuroblastoma cells were also observed. The ethanol extract of AC was orally administered to mice 30 min. prior to testing and ECT was intraperitoneally injected. AC and ECT treatment did not change locomotor activities as well as activities on the rota-rod, which indicates that they did not cause a sedative and myorelaxation effect. AC and ECT treatment increased threshold of convulsion induced by electroshock. AC treatment also inhibited convulsion induced by pentylenetetrazole. In the case of strychnine however, only high dose of AC treatment inhibited convulsion. AC and ECT treatment increased the $Cl^-$ influx into the intracellular area in a dose-dependent manner. On the other hand, bicuculline, a GABA antagonist, inhibited the $Cl^-$ influx induced by AC and ECT. These results indicate that ECT induces the anticonvulsive effect of AC extract through the GABAergic neuron.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.53-57
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• 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
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• v.27 no.3
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• pp.273-277
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• 2004

In previous studies for the development of new anticonvulsants, we found that N-Cbz-$\alpha$-amino-N-alkylsuccinimides exhibited significant anticonvulsant activities in the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests, and also their anticonvulsant activities were dependent on the N-alkyl substituents existent in their structures. Based on these estimations, N-Cbz-$\alpha$-amino-N-hydroxysuccinimide and various N-Cbz-$\alpha$-amino-N-alkoxysuccinimides were prepared in order to develop more active anticonvulsants and to examine the effects of N-hydoxy or N-alkoxy groups on their anticonvulsant activities. The (R)-or (S)-N-Cbz-$\alpha$-amino-N-hydroxysuccinimide and N-Cbz-$\alpha$-amino-N-alkoxysuccinimides were prepared from the corresponding (R)-or (S)-N-Cbz-aspartic acid through the known synthetic procedures. Their anticonvulsant activities in the MES and PTZ test were evaluated. All of these compounds except 3a showed significant anticonvulsant activities against the PTZ test, but these compounds were not active in the MES test. The most active compound in the PTZ test was (R)-N-Cbz-$\alpha$-amino-N-benzyloxysuccinimide (ED$_{50}$=62.5 mg/kg). In addition, the anti-convulsant activities of these compounds were dependent on their N-substited groups. The order of anticonvulsant activity against the PTZ test, as judged from the ED50 values for (R) series was N-benzyloxy > N-hydroxy > N-isopropoxy > N-methoxy > N-ethoxy; for the (S) series N-ethoxy > N-benzyloxy > N-methoxy > N-isopropoxy.y.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.151-155
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• 2004

In our previous studies for the development of new anticonvulsant of broad spectrum, we found that N-cbz-$\alpha$-aminoglutarimides showed significant anticonvulsant activities of broad spectrum enough to be recommended for the new anticonvulsants and their anticonvulsant activities were dependent on their imide substituent groups. Based on these results, various N-cbz--$\alpha$-amino-N-alkoxyglutarimides, where the imide N-H was substituted with the hydroxy and alkoxy group, were prepared and evaluated for their anticonvulsant activities using the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests and also the rotorod test. A series of (R) or (S)-N-cbz--$\alpha$-amino-N-alkoxyglutarimides could be prepared from the corresponding (R) or (S)-N-cbz-glutamic acid following the usual synthetic procedure. Among them, (R)-N-cbz--$\alpha$-amino-N-hydroxyglutarimide ($ED_{50}$=86.25 mg/kg) was most active in the MES test. In the case of the PTZ test, (R)-N-cbz--$\alpha$-amino-N-benzyloxyglutarimide ($ED_{50}$= 62.5 mg/kg) was most active. Among the tested compounds, 2a-c, 3a, and 3b showed anticonvulsant activities in the MES and PTZ test. All of the tested compounds, except 2f and 3f, showed significant anticonvulsant activities in the MES or PTZ test. In addition, the neurotoxicities of these compounds were comparable to other anticonvulsant drugs.

• Natural Product Sciences
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• v.23 no.1
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• pp.40-45
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• 2017

Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on $Cl^-$ influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular $Cl^-$ influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.

• Toxicological Research
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• v.8 no.2
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• pp.161-170
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• 1992

The objectives of this sutdy were to investigate the effects of 8-fluorociprofloxacin(8-FCP) on the central nervous system (CNS) and to compare with those of ciprofloxacin(CP). The $LD_{50}$ values of intravenous 8-FCP were similar or slightly lower in rat (M;203.6mg/kg, F;186.1mg/kg)and markedly lower in mice (M;126.5mg/kg, F;163.1mg/kg), as compared to those of CP. However, no recognizable differences in the clinical signs and recovery were found between 8-FCP and CP in both species. In combination with fenbufen, the convulsive liability of 8-FCP was higher than that of CP. At an intravenous dose of 10mg/kg, 8-FCP provoked convulsive signs and subsequent death in mice, whereas CP produced convulsion at a dose of 40mg/kg. The hexobabital -induced sleeping time was markedly lengthened by the oral administration of 8-FCP, but slightly increased by CP. In addition, the two quinolone derivatives had analgesic effects. The analgesic activity of 8-FCP was approximately two times higher than that at CP. However, both 8-FCP and CP had little effects of pentylenetetrazole-or strychnine-induced convulsion and muscle relaxation. Our finding that 8-FCP had more remarkable CNS effects than CP strongly suggests that there should be differences in the pharmacokinetic characteristics and/or in the binding affinity for specific biologic targets, or receptors, in the CNS.