Abstract |
Several diaminodiphenyl analogs were assessed in vivo for their capacity to inhibit seizure induction and propagation in rodents. Both 3,4'- and 4,4'-diaminodiphenyl compounds prevented seizures for as long as 4h after maximal electric shock induction. 4,4'-Diphenyl compounds bridged by a methylene, sulfide, or carbonyl linker also attenuated focal seizure acquisition in a kindling model. Of these analogs, based upon data generated in two rodent species, 4,4'-thiodianiline (1) was identified as the most active compound, significantly reducing seizure staging scores and after-discharge duration for several hours after systemic administration. All compounds were devoid of acute in vivo neurotoxicity at doses well above those required for anticonvulsant activity.
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Authors | David R Worthen, Aimee K Bence, James P Stables, Peter A Crooks |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 19
Issue 17
Pg. 5012-5
(Sep 01 2009)
ISSN: 1464-3405 [Electronic] England |
PMID | 19632831
(Publication Type: Journal Article)
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Chemical References |
- Aniline Compounds
- Anticonvulsants
- Biphenyl Compounds
- 4,4'-thiodianiline
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Topics |
- Aniline Compounds
(chemistry, pharmacology, toxicity)
- Animals
- Anticonvulsants
(chemistry, pharmacology, toxicity)
- Biphenyl Compounds
(chemistry, pharmacology, toxicity)
- Disease Models, Animal
- Male
- Mice
- Rats
- Rats, Sprague-Dawley
- Seizures
(chemically induced, drug therapy)
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