Thirty 1-aryl-5-dimethylamino-1-penten-3-one hydrohalides and related compounds were prepared as candidate anticonvulsants and evaluated in maximal electroshock seizure (MES), subcutaneous pentylenetetrazole threshold, and neurotoxicity screens. Following administration by the intraperitoneal route, many of the compounds were active in the MES screen, whereas only 10% of the Mannich bases afforded protection in the subcutaneous pentylenetetrazole test. Quantitation of half of the compounds prepared revealed that many had activity comparable with that of clinically useful drugs in the MES screen. The anticonvulsant properties of eight of the compounds following oral administration were reduced considerably or abolished compared with those following intraperitoneal administration. Various synthetic strategies for future development of potential anticonvulsants are outlined.