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Anticonvulsant Activity of N ‐Palmitoylethanolamide, a Putative Endocannabinoid, in Mice
Author(s) -
Lambert Didier M.,
Vandevoorde Séverine,
Diependaele Gérald,
Govaerts Sophie J.,
Robert Annie R.
Publication year - 2001
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2001.41499.x
Subject(s) - palmitoylethanolamide , anandamide , pentylenetetrazol , pharmacology , anticonvulsant , cannabinoid , endocannabinoid system , ed50 , chemistry , medicine , phenytoin , epilepsy , cannabinoid receptor , antagonist , receptor , psychiatry
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 (ED 50 ) 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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