Anticonvulsant Activity of N‐Palmitoylethanolamide, a Putative Endocannabinoid, in Mice

DM Lambert, S Vandevoorde, G Diependaele… - …, 2001 - Wiley Online Library
DM Lambert, S Vandevoorde, G Diependaele, SJ Govaerts, AR Robert
Epilepsia, 2001Wiley Online Library
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
(ip) 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 …
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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