Compounds > n-(4-amino-2-chlorophenyl)phthalimide

n-(4-amino-2-chlorophenyl)phthalimide and Seizures

n-(4-amino-2-chlorophenyl)phthalimide has been researched along with Seizures* in 1 studies

Other Studies

1 other study(ies) available for n-(4-amino-2-chlorophenyl)phthalimide and Seizures

Article	Year
Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore. Journal of medicinal chemistry, 2000, Apr-06, Volume: 43, Issue:7 A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal (ip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 microM, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 microM excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models. Topics: Administration, Oral; Animals; Anticonvulsants; Batrachotoxins; Cerebral Cortex; Convulsants; Electroshock; Excitatory Amino Acid Agonists; gamma-Aminobutyric Acid; In Vitro Techniques; Ion Channel Gating; Kainic Acid; Magnesium Deficiency; Mice; N-Methylaspartate; Patch-Clamp Techniques; Pentylenetetrazole; Phenytoin; Phthalimides; Rats; Seizures; Sodium Channel Blockers; Structure-Activity Relationship; Synaptosomes; Tumor Cells, Cultured	2000

Article

Year

Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore.

Journal of medicinal chemistry, 2000, Apr-06, Volume: 43, Issue:7

A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal (ip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 microM, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 microM excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models.

Topics: Administration, Oral; Animals; Anticonvulsants; Batrachotoxins; Cerebral Cortex; Convulsants; Electroshock; Excitatory Amino Acid Agonists; gamma-Aminobutyric Acid; In Vitro Techniques; Ion Channel Gating; Kainic Acid; Magnesium Deficiency; Mice; N-Methylaspartate; Patch-Clamp Techniques; Pentylenetetrazole; Phenytoin; Phthalimides; Rats; Seizures; Sodium Channel Blockers; Structure-Activity Relationship; Synaptosomes; Tumor Cells, Cultured

2000