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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of GABA-modulating drugs were assessed in a pharmacological study of amygdala-kindled seizures in the rat. Fully-kindled subjects were tested with a randomized dose regimen, including drug vehicle, for each of seven drugs. Afterdischarge duration, motor seizure latency, motor seizure duration and motor seizure stage were scored. The GABA synthesis inhibitor, 3-mercaptopropionic acid, the GABA antagonist, bicuculline, and the chloride ionophore blocker, picrotoxin, all decreased motor seizure latency, but did not otherwise alter the kindled seizure duration or seizure stage. The inhibitor of GABA metabolism, gamma-vinyl-GABA, and pentobarbital, which competes for the picrotoxin binding site, both antagonized kindled seizures. Gamma-vinyl-GABA, however, did not appear to antagonize kindled seizures by a specific effect on GABA neurotransmission. The GABA agonists, imidazole acetic acid and [alpha-(chloro-4'phenyl)fluoro-5-hydroxy-2-benzylidene-amino]-4-butyramide (SL 76-002), did not alter the kindled seizures. The results of these experiments are not consistent with the hypothesis that kindled seizures result from a loss of GABA-mediated inhibition; however, GABA may have a role in the modulation of kindled seizure activity.
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PMID:Pharmacological investigation of gamma-aminobutyric acid (GABA) and fully-developed generalized seizures in the amygdala-kindled rat. 706 9

Out of fourteen compounds reported here only four [N-valproyl GABA (V.GABA), N-phthaloyl GABA (P.GABA), gamma-phthalimido N-amyl butyramide (PGA) and gamma-phthalimido N-phenyl butyramide (PGP)] gave significant protection to all the four components of maximal electroshock-induced seizures (MES) in mice. It appeared that substitution of either amino or carboxylic or both groups of gamma-aminobutyric acid (GABA) with bulkier groups like aliphatic or aromatic carbons usually produced effective anticonvulsant GABA derivatives. V.GABA and P.GABA were the most effective anticonvulsant GABA derivatives in protecting all the components of MES-induced seizures. They were 2.3 and 1.5 times potent than sodium valproate in molar ratio, but P.GABA has low therapeutic index when compared to V.GABA. The observed anticonvulsant activity may be due to enhanced GABA concentration in the CNS. Probably, the active compound (V.GABA) crossed the blood brain barrier and hydrolysed to GABA and valproic acid to bring about its anticonvulsant action.
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PMID:Effect of GABA analogues on various components of maximum electroshock-induced seizures in mice. 807 Aug 45

The anticonvulsant activity of a homologous series of (+/-)-p-fluoro-phenyl alcohol amides is described. The compounds (+/-)-2-hydroxy-2-(4'-fluorophenyl)butyramide (2), (+/-)-3-hydroxy-3-(4'-fluorophenyl)pentanamide (4) and (+/-)-4-hydroxy-4-(4'-fluorophenyl)hexanamide (6) were prepared and tested. Compounds 2, 4 and 6 exhibited a similar significant activity in seizures provoked by pentylenetetrazol. Incorporation of fluorine in the para position of the phenyl ring, increased both their potency at the time of the peak drug effect and the duration of their anticonvulsant activity.
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PMID:Synthesis and pharmacological evaluation of a new homologous series of (+/-)-p-fluoro-phenyl alcohol amide anticonvulsants. 960 75

The anticonvulsant activity of a homologous series of p-chlorophenyl alcohol amides is described. The new compounds (+/-)-2-hydroxy-2-(4'-chlorophenyl)-butyramide (2), (+/-)-3- hydroxy-3-(4'-chlorophenyl)pentanamide (4) and (+/-)-4-hydroxy-4-(4'-chlorophenyl)-hexanamide (6), were prepared and tested for their anticonvulsant activity. Compounds 2, 4, and 6 exhibited significant activity in seizures provoked by pentylenetetrazol. Chlorine in the para position of the phenyl ring increased both their potency at the peak effect and the duration of their anticonvulsant activity. The anticonvulsant activities of (+/-)-3-hydroxy-3-phenylpentanamide (3) and compound 4 were antagonized by DL-baclofen. This, and the protecting activity of 3 in the genetic-absence-epilepsy rats of the Strasbourg model suggest that the phenyl alcohol amides could be GABAB receptor antagonists.
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PMID:Synthesis of a new homologous series of p-chlorophenyl alcohol amides, their anticonvulsant activity and their testing as potential GABAB receptor antagonists. 974 5

In this study, 15 omega-(1H-imidazol-1-yl)-N-phenylacetamide, propionamide and butyramide derivatives having methoxyl, methyl, nitro and chloro in ortho position of N-phenyl ring or without any substituent have been realized by two-step synthesis. Their anticonvulsant activity was determined against seizures induced by maximal electroshock (MES). The most active compound in the series was 2-(1H-imidazol-1-yl)-N-(o-chlorophenyl)acetamide.
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PMID:Synthesis and anticonvulsant activity of some omega-(1H-1-imidazolyl)-N-phenylalkanoic acid amide derivatives. 1198 98

The anticonvulsant activity of a homologous series of DL-dichlorophenyl alcohol amides is described. The compounds DL-2-hydroxy-2-(3',4'-dichlorophenyl) butyramide (4, CAS 620950-11-0), DL-3-hydroxy-3-(3',4'-dichlorophenyl) pentanamide (5, CAS 620950-15-4) and DL-4-hydroxy-4-(3',4'-dichlorophenyl) hexanamide (6, CAS 620950-17-6 ) were prepared and tested. Compounds 4, 5 and 6 exhibited a significant activity in seizures induced by pentetrazol. Incorporation of chlorine in the phenyl ring increased their potency. Compound 4 exhibited a slightly lower activity than the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis and pharmacological evaluation of some DL-dichlorophenyl alcohol amides anticonvulsants. 1564 66

The anticonvulsant activity of some DL-hydroxybenzenamides is described. The following compounds from this series were prepared and tested: DL-2-hydroxy-2-(3'-bromophenyl)butyramide (4, CAS 620950-12-1), DL-2-hydroxy-2-(4'-bromophenyl)butyramide (5, CAS 620950-13-2), DL-2-hydroxy-2-(3'-nitrophenyl)butyramide (6, CAS 620950-14-3), DL-2-hydroxy-2-phenyl hexanamide (7, CAS 63002-05-1), DL-2-hydroxy-2-(3',4'-dichlorophenyl)hexanamide (8, CAS 863976-06-1), DL-3-hydroxy-3-(4'-bromophenyl)pentanamide (9, CAS 620950-16-5), DL-3-hydroxy-3-phenyl-heptanamide (10, CAS 863976-08-3) and DL-4-hydroxy-4-(4'-bromophenyl)hexanamide (11,CAS 620950-18-7). Compounds 4, 5, 9 and 11 exhibited significant activity in seizures induced by pentylenetetrazol. Incorporation of bromine in the phenyl ring increased their potency. Compounds 4, 5, 9 and 11 exhibited a similar anticonvulsant activity as the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis of DL-hydroxybenzenamides as anticonvulsants. 1848 5

DL-2-Hydroxy-2-phenyl butyramide (1, CAS 52839-87-9), DL-3-hydroxy-3-phenyl pentanamide (2, CAS 131802-69-2) and DL-4-hydroxy-4-phenyl hexanamide (3, CAS 67880-30-2) are anticonvulsants. Searching for more active compounds, some DL-fluorobenzenamides were prepared and tested: DL-2-hydroxy-2-(3'-trifluoromethylphenyl)butyramide (4), DL-2-Hydroxy-2-4'-trifluoromethylphenyl) butyramide (5, CAS 620950-10-9), DL-2-hydroxy-2-[3',5'-bis(trifluoromethyl)phenyl]butyramide (6, CAS 620950-09-6), DL-3-hydroxy-3-(3'-trifluoromethylphenyl) pentanamide (7), DL-3-hydroxy-3-(4'-trifluoromethylphenyl)pentanamide (8), and DL-3-hydroxy-3-[3',5'-bis(trifluoromethyl)phenyl]pentanamide (9, CAS 863976-07-2). Compounds 4-9 exhibited anticonvulsant activity in seizures induced by pentylenetetrazol in mice. Incorporation of trifluoromethyl groups in the phenyl ring of 1, 2 and 3 increased their potency. Compounds 4, 6 and 9 exhibited a similar anticonvulsant activity as the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis of DL-fluorobenzenamides as anticonvulsants. 1854 Apr 76

Despite the availability of 14 new antiepileptic drugs (AEDs), about 30% of epileptic patients are not seizure-free. Consequently there is substantial need to develop new effective AEDs. A novel class of aromatic amides composed of phenylacetic acid or branched aliphatic carboxylic acids, with five to nine carbons in their carboxylic moiety, and aminobenzenesulfonamide were synthesized and evaluated in the anticonvulsant rat-maximal electroshock (MES) and subcutaneous metrazol seizure (scMet) tests. Fourteen of the synthesized amides had an anticonvulsant ED(50) of <50 mg/kg in the rat-MES test. The amides 2-methyl-N-(4-sulfamoylphenyl)butyramide (10), 2-ethyl-N-(4-sulfamoylphenyl)butyramide (11), and 3,3-dimethyl-N-(4-sulfamoylphenyl)butyramide (15) were the most potent compounds possessing MES-ED(50) values of 7.6, 9.9, and 9.4 mg/kg and remarkable protective index (PI = TD(50)/ED(50)) values of 65.7, 50.5, and 53.2, respectively. These potent sulfanylamides caused neural tube defects only at doses markedly exceeding their effective dose. The anticonvulsant properties of these compounds make them potential candidates for further development as new, potent, and safe AEDs.
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PMID:Syntheses and evaluation of anticonvulsant profile and teratogenicity of novel amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide. 2042 Mar 84