N-palmitoylethanolamide derivatives: synthesis and studies on anticonvulsant and antidepressant activities

A series novel of N-palmitoylethanolamide derivatives was synthesized and screened for their anticonvulsant and antidepressant activities. Anticonvulsant activities and neurotoxicities of compounds when injected intraperitoneally (i.p.) were determined by maximal electroshock seizure (MES) test and a rotarod test, respectively, in mice. Only four of the synthesized compounds (3a, 3b, 3c, and 3d) showed anticonvulsant activity at a dose of 100 mg/kg. Six compounds showed reduced immobility durations during the forced swimming test at a dose of 10 mg/kg, indicative of antidepressant activity. Among the compounds, N-(3-hydroxypropyl)cinnamamide (3a) was the most promising compound and significantly reduced the duration of immobility duration by 23.36% at a dose of 10 mg/kg compared with the control (P < 0.01).