• Archives of Pharmacal Research
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• 제14권2호
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• pp.172-175
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• 1991

Abnormality in the central noradrenergic system may be related to the seizure prone state in the genetically epilepsy prone rats (GEPR). The present work deals with the characterization of the deficit in noradrenergic system if susceptitibility and intensity of seizure are dependent on central noradrenregic activities by comparing the activities of dopamine $\beta$-hydroxylase (DBH) which hydroxylates dopamine into noradrenaline. DBH activities were measured in 5 areas of brain of normal rats, native GEPR and severe GEPR. The results suggest that lower DBH activities in the midbrain of GEPRs may positively be coupled to the susceptibility to seizure, whereas the same characteristics of the native or severe GEPR are not neccessarily in parallel with the intensity of seizure.

• Archives of Pharmacal Research
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• 제22권5호
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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.

• 대한약침학회지
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• 제26권4호
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• pp.327-337
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• 2023

Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.

• 생명과학회지
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• 제12권5호
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• pp.505-514
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• 2002

생쥐에서 최근 합성된 4가지 종류의 tropinone유도체들의 항경련 효과를 조사하기 위하여 pentylenetetrazole (PTZ) 및 Maximal Electroshock (MES)로 유발된 경련에 tropinone 유도체들이 경련상태에 미치는 효과를 관찰하였다. Troponine 유도체로는 화학구조가 다른 4가지 종류를 사용하였다(T-1:2,4-dipywolylmethenylnortropinone, T-2:2,L di phenylme thenylnortropinone, T-3 : 2,Ldifurfurylmetheny- Inortropinone, 74 : 2,4-dimetho xyphenylmethenylnortro- pinone). nZ 25 mg/kg을 복강 내로 투여 후 전신성 경련을 유발하였으며 tropinone 유도체를 전처치한 후 PTZ에 의한 경련의 변화를 관찰하였다. 대조군에 비하여 T-1과 T-2는 경련정도에 변화가 없었으나 T-3과 T-4는 유의하게 경련정도를 약화시켰다. PTZ에 의한 경련의 시작 시간은 T-4에서 유의하게 지연되어 T-4가 PTZ에 의한 경련에 항경련 효과가 있음을 나타내었다. MES로 경련을 유발한 경우에 있어서는 T-1이 경련정도를 유의하게 약화시켰으며 경련 후 회복시간도 T-1에서 가장 빨리 회복되는 특성을 보였다. 따라서 T-1이 MES에 의한 경련유발에 항경련 효과가 있음을 나타내었다. Troponine 유도체에 의한 경련 억제 효과와 경련과 동반되어 증가한다고 알려진 neuronal nitric oxide synthase (nNOS) 발현과의 관계를 알아보기 위하여 조직 단백질에서 Western blot을 하였다. 대조군에 비하여 PTZ 및 MES에 의해 경련을 유발한 생쥐에서 모두 해마부 및 전뇌피질부에서 nNOS가 증가하였다. Tropinone 유도체를 투여하지 않고 경련을 유발시킨 대조군에 비하여 tropinone 유도체를 투여한 군에서도 모두 nNOS의 발현이 해마부 및 전뇌피질부에서 증가되었다. MES로 경련을 유발한 생쥐에서 대조군에 비하여 T-1 및 T-4는 피질부에서 nNOS가 감소했으나 나머지군에서는 감소가 없었다. 이 상의 결과를 토대로 tropinone 유도체들은 경련유발의 자극 조건에 따라 항경련 효과가 다르게 나타났으며, PTZ유 발경련에서 2,4-dimethoxyphenylmethenylnortropinone의 항경련 효과가 가장 크고, MES 유발경련에서는 2,4-dipyrrolylmethenylnortropinone의 항경련 효과가 가장 크게 나타났다.

• Journal of Multimedia Information System
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• 제2권2호
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• pp.215-222
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• 2015

Epileptic Seizure is a popular brain disease in the world. It affects the nervous system and the activities of brain function that make a person who has seizure signs cannot control and predict his actions. Based on the Electroencephalography (EEG) signals which are recorded from human or animal brains, the scientists use many methods to detect and recognize the abnormal activities of brain. Tucker model is investigated to solve this problem. Tucker decomposition is known as a higher-order form of Singular Value Decomposition (SVD), a well-known algorithm for decomposing a matric. It is widely used to extract good features of a tensor. After decomposing, the result of Tucker decomposition is a core tensor and some factor matrices along each mode. This core tensor contains a number of the best information of original data. In this paper, we used Tucker decomposition as a way to obtain good features. Training data is primarily applied into the core tensor and the remained matrices will be combined with the test data to build the Tucker base that is used for testing. Using core tensor makes the process simpler and obtains higher accuracies.

• 약학회지
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• 제30권4호
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• pp.163-168
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• 1986

Thirteen compounds were synthesized by condensing the N-heterocyclic amines (piperidine, pyrrolidine, morpholine) and secondary aliphatic amines (dimethylamine, diethylamine) with 3,4-methylenedioxyphenylalkenoic acid chlorides for developing CNS depressants. Among them, N, N-diethyl-3,4-methylenedioxycinnamamide (IX) and N, N-dimethyl-5-(3,4-methylenedioxyphenyl)-2, 4-pentadienoic acid amicle (XII) exhibited strong activity in antagonism against pentylenetetrazole-induced convulsion, strychnine-induced convulsion and maximal electroshock seizure. N, N-Dimethyl-3, 4-methylenedioxycinnamide (VIII) showed more potent activity in antagonism against strychnine-induced convulsion and maximal electroshock seizure and in the prolongation of hexobarbital sleeping time.

• BMB Reports
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• 제32권4호
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• pp.339-344
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• 1999

We studied the effects of ginsenosides in immature rats based upon the previous results that ginseng has a suppressive or anticonvulsive activity. To examine the suppressive effect of ginsenosides on kainic acid-induced seizures, the severities and frequencies were observed for 4 h after injection of kainic acid (KA; i.p., 2 mg/kg b.w.) using 10-day-old male Sprague-Dawley rats ($22{\pm}2\;g$). Protopanaxadiol saponins such as ginsenoside-Rb1 (Rb1), ginsenoside-Rb2 (Rb2), ginsenoside-Rc (Rc), and ginsenoside-Rd(Rd) generally reduced the seizure activities while protopanaxatriol saponins such as ginsenoside-Rg1 (Rg1) and ginsenoside-Re (Re) rather increased stereotypic "paddling-like" movements. When vinyl-GABA (v-G) was injected together with Rb1 or Rc, KA-induced seizure severities were additionally reduced only by the injection of Rc, but not by Rb1. The level of gamma isozyme of protein kinase C (PKC-${\gamma}$) in the hippocampus increased about three times as much as that of normal rats at 4 h after KA injection. The increased level of PCK-${\gamma}$ by KA was significantly reduced to about 35% by the coinjection with v-G alone, but it was not changed by v-G together with Rb1 or Rc. The increased level of PKC-${\gamma}$ at 4 h after injection of KA was not consistent with the reduction of seizure severities between Rb1 and Rc. These results suggest that Rc and Rb1 may reduce seizure severity independent of PKC-${\gamma}$ levels, and Rc may additionally act with v-G regarding the GABA metabolism during the stage of KA-induced seizures in the immature rats.

• Archives of Pharmacal Research
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• 제29권6호
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• pp.459-463
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• 2006

Previous studies on the anticonvulsant activity of $N-Cbz-{\alpha}-aminoglutarmides$ have shown that the derivatives of $N-Cbz-{\alpha}-amino-N-alkoxy$ glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of $N-Cbz-{\alpha}-amino-glutarimidooxy$ carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of $N-Cbz-{\alpha}-amino-glutarimidooxy$ acetic acid 3a $(ED_{50}\;=\;42.9\;mg/kg)$.

• Annals of Clinical Neurophysiology
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• 제2권1호
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• pp.27-30
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• 2000

Reflex epilepsies are distinct but not clearly understood clinical entity. Various cerebral activities induced by simple stimulation including visual, auditory, somatosensory stimulation, as well as diverse functional tasks such as reading, calculation, complex thinking are believed to be seizure-inducing factors. We experienced two patients whose seizures were readily precipitated by complex, strenuous thinking. Both patients was teen-aged boy at the onset of seizure(13, and 15 years of age each) with normal physical and mental growth. Although first seizure was precipitated by watching TV and playing puzzles in each patient, initial diagnosis was idiopathic generalized epilepsy, possibly juvenile myoclonic epilepsy( JME). For the first few years, seizures were infrequent but mostly precipitated by the tasks needs concentration such as playing computer games, decision-making, mathematics, reading, or during the examination. EEG revealed various thinking process including reading hard books, drawing complex figure, complex calculation induced epileptic discharges even if it usually needs certain period of concentration. Phenytoin, valproic acid, clonazepam, vigabatrin, and lamotrigine sometimes abated their seizures but none of these made them seizure-free. Complex reflex epilepsy induced by thinking was proposed to be a separate type of epilepsy or a variant of JME. Age, sex, stereotypic seizure-inducing factors, clinical course, and refractory epilepsies in these patients highly suggested this type of epilepsy as a variant of JME but its refractoriness and unique provocation still needs more speculation.

• Archives of Pharmacal Research
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• 제21권6호
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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.