Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice

Purpose: The purpose of this study was to evaluate in mice the anticonvulsa nt potential of N-palmitoylethanolamide, a putative endocannabinoid that ac cumulates in the body during inflammatory processes. Methods: N-palmitoylethanolamide was injected intraperitoneally (i.p.) in m ice and evaluated for anticonvulsant activity [in maximal electroshock seiz ure (MES) and chemical-induced convulsions] and for neurologic impairment ( rotorod). It was compared with anandamide and with different palmitic acid analogues as well as with reference anticonvulsants (AEDs) injected under t he same conditions. Results: The MES test showed, after i.p. administration to mice, that N- pa lmitoylethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutane ous pentylene-tetrazol test and in the 3-mercaptropropionic acid test, it w as effective only against tonic convulsions. N-palmitoylethanolamide was de void of neurologic impairment less than or equal to 250 mg/kg, yielding a h igh protective index. Conclusions: N-palmitoylethanolamide, an endogenous compound with antiinfla mmatory and analgesic activities, is a potent AED in mice. Its precise mech anism of action remains to be elucidated.