Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some of appropriate aminoisopropanoloxy derivatives of 4-xanthone were tested for their effect on circulatory system (protection against adrenaline-, barium-, and calcium chloride-induced arrhythmias, as well as hypotensive activity and acute toxicity). The most prominent hypotensive activity was demonstrated by (+/-)-1-[4-(hydroxyethyl)-1-(piperazinyl)]-3-(4-xanthonoxy)-2-propanol dihydrochloride (II), which diminished arterial blood pressure by about 40% during one hour observation. The investigated compounds did not prevent adrenaline- and barium-induced arrhythmias. In calcium-induced model of arrhythmia compound II slightly intensified blocks (about 7%), but delayed extrasystoles (37%), efficiently prevented bigeminy (70%, p <0.01) and diminished (53%, p <0.05) mortality of animals. All investigated compounds decreased heart rate by 10 - 18%, prolonged P-Q section, QRS complex and Q-T interval. The most potent and significant negative chronotropic effect and markedly prolonged duration of P-Q section was demonstrated by compound II. The influence of investigated compounds on ECG components suggests that activity of compound IV is similar to class 1a anti-arrhythmic compounds according to Voughan-Williams classification of antiarrhythmic drugs, because of prolongation of P-Q and Q-T intervals and extension of QRS complex. Compounds II and IV were also evaluated for anticonvulsant activity in the maximal electroshock seizures (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The anti-MES activity in mice was found for IV, which in a dose of 100 mg/kg within 0.5 h after ip administration showed 75% anticonvulsant protection with 50% neurotoxicity.
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PMID:Antiarrhythmic and antihypertensive activity of some xanthone derivatives. 1864 59

A series of 1,4-piperazine derivatives was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The compounds were only moderately effective. The anticonvulsant activity was accompanied by neurotoxicity. 1-[(4-Chlor-3-methylphenoxy)-acetyl]-4-(2-methoxyphenyl)-piperazine was also evaluated in six hertz seizure test (6-Hz) and showed good activity. At the dose of 100 mg/kg b. w. the compound produced 100% protection after 0.5 h without neurotoxic effect.
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PMID:Preliminary evaluation of anticonvulsant activity and neurotoxicity of some 1,4-substituted piperazine derivatives. 1989 54

In the present study the series of spirosuccinimides with the aromatic ring at the imide nitrogen atom was synthesized. All the compounds were tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. The neurotoxic properties were determined applying the rotorod test (TOX). The most active were N-(2-methoxyphenyl)- [V] and N-(4-chlorophenyl-amino)-2-azaspiro[4.5]decane-1,3-dione [XI] that inhibited seizures at a dose of 100 mg/kg in the scPTZ and MES tests, respectively. The other derivatives, namely N-(3-methoxyphenyl)- [VI], N-(1-phenylethyl)- [VIII], N-(diphenylmethyl)- [IX], N-(6-aminopyridin-2-yl)- [XII] 2-azaspiro[4.5]decane-1,3-diones, and the compounds with the methyl group at position-3 [XIV, XVII] or at position-4 [XVIII] of the cyclohexane ring showed anti-MES and/or anti-scPTZ protections at doses of 300 mg/kg. The results obtained revealed that anticonvulsant activity depended on the substitution mode of the aromatic ring as well as the kind of spacer between imide nitrogen atom and aromatic system.
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PMID:Synthesis and anticonvulsant activity of new spirosuccinimides differently substituted at the imide nitrogen atom. 2005 May 30

A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.
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PMID:Synthesis and research of benzylamides of some isocyclic and heterocyclic acids as potential anticonvulsants. 2392 92

A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.
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PMID:Synthesis and anticonvulsant activity of novel purine derivatives. 2506 8

A series of new N-(2,5-dimethylphenoxy)- and N-(2,3,5-trimethylphenoxy)alkylaminoalkanols [I-XVII] was synthesized and evaluated for anticonvulsant activity. Pharmacological tests included maximal electroshock (MES) and subcutaneous pentetrazole seizure threshold (scMet) assays as well as neurotoxicity (TOX) evaluation in mice after intraperitoneal (i.p.) administration and/or in rats after oral (p.o.) administration. The most active compound was R-2N-[(2,3,5-trimethylphenoxy)ethyl]aminobutan-1-ol, which exhibited 100% activity in MES at the dose of 30 mg/kg body weight (mice, i.p.) and 75% activity in MES at 30 mg/kg b.w. (rats, p.o.) without neurotoxicity at the active doses.
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PMID:Synthesis and evaluation of anticonvulsant activity of N-(2,5-dimethylphenoxy)- and N-[(2,3,5-trimethylphenoxy)alkyl]aminoalkanols. 2585 Feb 4

New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study.
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PMID:Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents. 2693 19

A series of new benzothiazole derivatives containing dimethylpyrazole were synthesized and evaluated for their anticonvulsant activity, neurotoxicity and cytotoxicity by using the maximal electroshock (MES), rotarod neurotoxicity (TOX) and MTT colorimetric assay. Among the compounds studied, four compounds (6a, 6b, 6g and 6m) showed better anticonvulsant than the others at 300 mg/kg and they also showed anticonvulsant activity at the dose of 100 mg/kg. All the synthetic compounds showed lower neurotoxicity and little cytotoxicity, so that the compounds, which with better activities, also had higher protective index. In particular, the compound 6g, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-((2-fluorobenzyl)oxy)benzo[d]thiazole showed better activity with an ED50 value of 160.4 mg/kg and higher protective index (PI) values of 2.74 in the MES test than the standard drugs sodium valproate, which used as positive controls in this study. After that the compound 6g demonstrated antagonistic activity against seizures induced by pentylenetetrazol, which proved 6g maybe exert activity through effecting GABAergic neurotransmission.<br />.
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PMID:Design, Synthesis and Biological Evaluation of Benzo[D]Thiazole with Dimethylpyrazol Derivatives. 3175 76


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