Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid.
OBJECTIVE
The purpose of this study was to determine whether N-palmitoylethanolamide (PEA), a putative endocannabinoid, would be effective against kindled amygdaloid seizures. For a comparison with earlier work, we also tested the effectiveness of PEA against pentylenetetrazol (PTZ)-induced convulsions.


METHODS
Kindling electrodes were implanted bilaterally in the amygdala in 32 Long-Evans rats. After the kindling of generalized (stage 5) seizures, the effects of PEA administration [i.p.; 1, 10, 100 mg/kg in dimethylsulfoxide (DMSO)] were evaluated for anticonvulsant activity. PEA (40 mg/kg, i.p. in DMSO) also was tested for anticonvulsant activity against PTZ-induced convulsions (75 mg/kg, i.p.).


RESULTS
After i.p. administration of PEA, kindled rats displayed an increased latency to clonus at the 1-mg/kg dose. No other dose-dependent effects were noted. When tested against PTZ-induced convulsions, PEA protected against tonic convulsions and prolonged the latency between convulsive episodes.


CONCLUSIONS
PEA produces antiepileptic effects, but does not completely suppress seizures. The mechanism of action of PEA remains to be defined.
Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Aaron H
AH
Sheerin
Xia
X
Zhang
Deborah M
DM
Saucier
Michael E
ME
Corcoran
D000577:Amides; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D063388:Endocannabinoids; D004983:Ethanolamines; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010169:Palmitic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010433:Pentylenetetrazole; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012997:Solvents / Q000008:administration & dosage
D000577:Amides; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D014677:Pharmaceutical Vehicles; D012997:Solvents; C005958:palmidrol; D010433:Pentylenetetrazole; D004121:Dimethyl Sulfoxide