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Various 1,4-substituted derivatives of piperazine (I-XII) were synthesized and evaluated for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (ScMet)--induced seizures and for neurotoxicity (TOX) in the rotorod test in mice and rats. The most promising compounds seem to be 1-[(2,4,6-trimethyl)-phenoxyethyl]-4-(2-hydroxyethyl)-piperazine dihydrochloride (II) and 1,4-bis-[(4-chloro-3-methyl)-phenoxyethyl]-piperazine dihydrochloride (X) which displayed anti-MES activity with their protective index (PI) higher than that for valproate II (rats), X(mice)).
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