Modulation of pentylenetetrazol-induced seizures by prostaglandin E2 receptors.
There is evidence that prostaglandin E2 (PGE2) facilitates the seizures induced by pentylenetetrazol (PTZ), but the role of PGE2 receptors (EPs) in the development of seizures has not been evaluated to date. In the current study we investigated whether selective EP ligands alter PTZ-induced seizures in adult male Wistar rats by electrographic methods. Selective antagonists for EP1 (SC-19220, 10 nmol, i.c.v.), EP3 (L-826266, 1 nmol, i.c.v.) and EP4 (L-161982, 750 pmol, i.c.v.) receptors, and the selective EP2 agonist butaprost (100 pmol, i.c.v.) increased the latency for clonic and generalized tonic-clonic seizures induced by PTZ. These data constitute pharmacological evidence supporting a role for EPs in the seizures induced by PTZ. Although more studies are necessary to fully evaluate the anticonvulsant role these compounds and their use in the clinics, EP ligands may represent new targets for drug development for convulsive disorders.
Oliveira
M S
MS
Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Furian
A F
AF
Rambo
L M
LM
Ribeiro
L R
LR
Royes
L F F
LF
Ferreira
J
J
Calixto
J B
JB
Mello
C F
CF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D010433:Pentylenetetrazole; D011448:Prostaglandin Antagonists / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology
D011448:Prostaglandin Antagonists; D018078:Receptors, Prostaglandin E; D010433:Pentylenetetrazole