User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

Primary tabs

Lambert, Didier [UCL] Vandevoorde, Severine [UCL] Diependaele, G Govaerts, Sophie [UCL] Robert, Annie [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2001
Journal information "Epilepsia" - Vol. 42, no. 3, p. 321-327 (2001)
Peer reviewed yes
issn 0013-9580
Publication status Publié
Affiliations UCL - MD/FARM - Ecole de pharmacie
UCL - MD/ESP - Ecole de santé publique
MESH Subject Animals ; Anticonvulsants - pharmacology ; Cannabinoids - pharmacology ; Convulsants - administration & dosage ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electroshock ; Endocannabinoids ; Male ; Mice ; N-Methylaspartate - administration & dosage ; Palmitic Acids - pharmacology ; Propionates - administration & dosage ; Seizures - chemically induced - etiology - prevention & control ; Valproic Acid - pharmacology
Links
  1. Bachur, J Biol Chem, 240, 1019 (1965)
  2. Schmid, Prog Lipid Res, 29, 1 (1990)
  3. Devane, Science, 258, 1946 (1992)
  4. Di Marzo, Curr Med Chem, 6, 721 (1999)
  5. Facci, Proc Natl Acad Sci U S A, 92, 3376 (1995)
  6. Showalter, J Pharmacol Exp Ther, 278, 989 (1996)
  7. Sheskin, J Med Chem, 40, 659 (1997)
  8. Lambert Didier M, DiPaolo Federica G, Sonveaux Pierre, Kanyonyo Martial, Govaerts Sophie J, Hermans Emmanuel, Bueb Jean-Luc, Delzenne Nathalie M, Tschirhart Eric J, Analogues and homologues of N-palmitoylethanolamide, a putative endogenous CB2 cannabinoid, as potential ligands for the cannabinoid receptors, 10.1016/s1388-1981(99)00132-8
  9. Lambert, Curr Med Chem, 6, 757 (1999)
  10. Mazzari, Eur J Pharmacol, 300, 227 (1996)
  11. Jaggar, Pain, 76, 189 (1998)
  12. Aloe, Agents Actions, 39, C145 (1993)
  13. Barth, Exp Opin Ther Patents, 8, 301 (1998)
  14. Skaper, Proc Natl Acad Sci U S A, 95, 8375 (1998)
  15. Dewey, Pharmacol Rev, 38, 151 (1986)
  16. Consroe, Eur J Pharmacol, 21, 7 (1982)
  17. CONSROE P., MARTIN A., SINGH V., Antiepileptic Potential of Cannabidiol Analogs, 10.1002/j.1552-4604.1981.tb02623.x
  18. Ikeda, J Chromatogr, 575, 197 (1992)
  19. Kanyonyo, Pharmacol Toxicol, 82, 47 (1998)
  20. Masereel, Epilepsia, 38, 334 (1997)
  21. Lambert, Neuroreport, 5, 777 (1994)
  22. Porter R. J., Cereghino J. J., Gladding G. D., Hessie B. j., Kupferberg H. J., Scoville B., White B. G., Antiepileptic Drug Development Program, 10.3949/ccjm.51.2.293
  23. Braestrup, Brain Res Bull, 5, 681 (1980)
  24. Sugiura, Biochem Biophys Res Commun, 229, 58 (1995)
  25. Felder, Proc Natl Acad Sci U S A, 90, 7656 (1993)
  26. Cravatt, Science, 268, 1506 (1995)
  27. Huidobro-Toro, Proc Natl Acad Sci U S A, 93, 8078 (1996)
  28. Mendelson, Neuroreport, 10, 3237 (1999)
  29. Mechoulam, Nature, 389, 25 (1997)
  30. Venance, Nature, 376, 590 (1995)
  31. Pertwee, Curr Med Chem, 6, 635 (1999)
  32. Hampson, Proc Natl Acad Sci U S A, 95, 8268 (1998)
  33. Gulaya, Chem Phys Lipids, 97, 49 (1998)
  34. Lockard, Epilepsia, 17, 477 (1976)
  35. N Biochim Biophys Acta
  36. Bisogno Tiziana, Ventriglia Mariacarla, Milone Alfredo, Mariarosaria Mosca, Cimino Guido, Di Marzo Vincenzo, Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries of the sea urchin Paracentrotus lividus, 10.1016/s0005-2760(97)00009-x
  37. De Petrocellis, Neuroscience, 92, 377 (1999)
  38. Berdyshev, Eur J Pharmacol, 330, 231 (1997)
  39. Berdyshev, Life Sci, 63, PL125 (1998)
Bibliographic reference Lambert, Didier ; Vandevoorde, Severine ; Diependaele, G ; Govaerts, Sophie ; Robert, Annie. Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.. In: Epilepsia, Vol. 42, no. 3, p. 321-327 (2001)
Permanent URL http://hdl.handle.net/2078.1/8879