A novel class of "GABAergic" agents: 1-aryl-3-(aminoalkylidene)oxindoles.
Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles. Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dimethylamino)-ethylidene and N-methyl-2-pyrrolidinylidene side chains. The precise mechanism of action of these agents is unclear at this time; however, they are not GABA mimics and they do not affect GABA levels. Like other GABAergic agents, these compounds are potent enhancers of benzodiazepine binding and they antagonize cyclic GMP elevations induced by isoniazid. Compounds from this series may therefore have potential therapeutic utility as anticonvulsants or anxiolytics.
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Pfizer Central Research, Pfizer, Inc., Groton, Connecticut 06340.
Howard
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Koe
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BK
Weissman
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A
D015097:3-Mercaptopropionic Acid / Q000037:antagonists & inhibitors*; D000818:Animals; D005445:Flunitrazepam / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000037:antagonists & inhibitors*
D007211:Indoles; D011963:Receptors, GABA-A; D013438:Sulfhydryl Compounds; D005445:Flunitrazepam; D015097:3-Mercaptopropionic Acid