In vivo evaluation of diaminodiphenyls: anticonvulsant agents with minimal acute neurotoxicity.

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.

• 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)

Chemical References

• Aniline Compounds
• Anticonvulsants
• Biphenyl Compounds
• 4,4'-thiodianiline

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)