TI: Anticonvulsant activity of N-palmitoylethanolamide,
a putative endocannabinoid, in mice.
AU: Lambert,-D-M; Vandevoorde,-S; Diependaele,-G; Govaerts,-S-J;
Robert,-A-R
AD: Unite de Chimie pharmaceutique et de Radiopharmacie, Ecole
de Pharmacie, Universite catholique de Louvain, Brussels, Belgium. lambert@cmfa.ucl.ac.be
SO: Epilepsia. 2001 Mar; 42(3): 321-7
JN: Epilepsia-
PY: 2001
AB: 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-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.