Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.
OBJECTIVE
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-palmitoy]ethanolamide 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 < or = 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.
Lambert
D M
DM
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium. lambert@cmfa.ucl.ac.be
Vandevoorde
S
S
Diependaele
G
G
Govaerts
S J
SJ
Robert
A R
AR
D000577:Amides; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000494:pharmacology*; D003292:Convulsants / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D063388:Endocannabinoids; D004983:Ethanolamines; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage; D010169:Palmitic Acids / Q000494:pharmacology*; D011422:Propionates / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D014635:Valproic Acid / Q000494:pharmacology
D000577:Amides; D000927:Anticonvulsants; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D003292:Convulsants; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D011422:Propionates; D014635:Valproic Acid; D016202:N-Methylaspartate; C017526:3-methylthiopropionate; C005958:palmidrol