Selective Antiepileptic Effects of N‐Palmitoylethanolamide, a Putative Endocannabinoid

• Published in: Epilepsia (Copenhagen) Vol. 45; no. 10; pp. 1184 - 1188
• Main Authors: Sheerin, Aaron H., Zhang, Xia, Saucier, Deborah M., Corcoran, Michael E.
• Format: Journal Article
• Language: English
• Published: 350 Main Street , Malden , MA 02148 , USA and 9600 Garsington Road , Oxford , OX4 2XG , England Blackwell Science Inc 01.10.2004; Blackwell
• Subjects: Amygdala; Amygdala - drug effects; Amygdala - physiopathology; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Cannabinoid Receptor Modulators - administration & dosage; Cannabinoid Receptor Modulators - pharmacology; Cannabinoids - administration & dosage; Cannabinoids - pharmacology; Dimethyl Sulfoxide - administration & dosage; Dose-Response Relationship, Drug; Electric Stimulation; Electrodes, Implanted; Endocannabinoids; Ethanolamines; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Injections, Intraperitoneal; Kindling; Kindling, Neurologic - drug effects; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Neuroprotective agent; Palmitic Acids - administration & dosage; Palmitic Acids - pharmacology; Pentylenetetrazol; Pentylenetetrazole; Pharmaceutical Vehicles - administration & dosage; Pharmacology. Drug treatments; Rat; Rats; Rats, Long-Evans; Seizures - chemically induced; Seizures - physiopathology; Seizures - prevention & control; Solvents - administration & dosage; Nervous system diseases; Anticonvulsant; Kindling- Pentylenetetrazol-Amygdala-Rat; Epilepsy; Central nervous system disease; Cerebral disorder
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.0013-9580.2004.16604.x

Purpose: 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.