Drug Discov Ther. 2011;5(5):227-237. (DOI: 10.5582/ddt.2011.v5.5.227)

Design, synthesis, anticonvulsant screening and 5HT1A/2A receptor affinity of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones.

Dhanawat M, Das N, Shrivastava SK


In the present study, a series of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones derivatives (1-16) were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure test. Affinity towards receptor (5-HT1A/2A) was also studied. Their neurotoxicity was determined using the rotarod test. Structures of compounds were confirmed by spectroscopic methods. Compounds 1, 2, 5, 7, 9, and 10 exhibited significant anticonvulsant activity as compared to the standard drug phenytoin. Affinity toward receptor (5-HT1A/2A) was studied in vivo for compounds 1, 2, 5, 7, 9, and 10. Rectal body temperature, lower lip retractions and head twitch responses in Wistar rats/albino mice were determined for this purpose. The tested compounds showed affinity for 5-HT1A and 5-HT2A receptors (agonists/antagonists and presynaptic/postsynaptic). Replacement of piperazine by aniline derivatives provides good outcomes in terms of affinity for 5-HT1A/2A.

KEYWORDS: Epilepsy, anticonvulsant, acetamide, phenytoin, oxazolidine-2,4-dione, aniline, piperazine

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