Anticonvulsant Activity of N-Palmitoylethanolamide, a Putative Endocannabinoid, in Mice
Didier M. Lambert
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorSéverine Vandevoorde
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorGérald Diependaele
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorSophie J. Govaerts
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorAnnie R. Robert
Ecole de Santé publique, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorDidier M. Lambert
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorSéverine Vandevoorde
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorGérald Diependaele
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorSophie J. Govaerts
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, and
Search for more papers by this authorAnnie R. Robert
Ecole de Santé publique, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorAbstract
Summary: Purpose: The purpose of this study was to evaluate in mice the anticonvulsant potential of N-palmitoylethanolamide, a putative endocannabinoid that accumulates in the body during inflammatory processes.
Methods: N-palmitoylethanolamide was injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant activity [in maximal electroshock seizure (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 the same conditions.
Results: The MES test showed, after i.p. administration to mice, that N- palmitoylethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutaneous pentylenetetrazol test and in the 3-mercaptropropionic acid test, it was effective only against tonic convulsions. N-palmitoylethanolamide was devoid of neurologic impairment ≤250 mg/kg, yielding a high protective index.
Conclusions: N-palmitoylethanolamide, an endogenous compound with antiinflammatory and analgesic activities, is a potent AED in mice. Its precise mechanism of action remains to be elucidated.
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