Pain & Central Nervous System Week via NewsEdge :

2008 MAY 12 - (NewsRx.com) -- New investigation results, 'Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures,' are detailed in a study published in Epilepsy Research (see also Seizure Therapy). "Cyclooxygenases (COXs) are rate-limiting enzymes in the metabolic pathways in which arachidonic acid is converted to prostaglandins. COX-2 is the isoform induced at injury/inflammation sites and expressed constitutively in a few tissues, such as the central nervous system, and plays a role in neurodegenerative diseases associated with increased excitatory activity," scientists in Santa Maria, Brazil report.

"However, the role of COX-2 and its main product, prostaglandin E(2) (PGE(2)), in the convulsive states is not fully established. In this study we showed that the selective COX-2 inhibitor, celecoxib (at the dose of 2mg/kg, but not at the doses of 0.2 or 20mg/kg, p.o.), protects against the seizures induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.). The role of PGE(2) in the convulsions induced by PTZ was further investigated by administering anti-PGE(2) antibodies (4 microg/2 microl, i.c.v.), and assessing electroencephalographic changes induced by PTZ (PTZ, 60 mg/kg, i.p.). Anti-PGE(2) antibodies attenuated PTZ-induced seizures in rats. In addition, combining PGE(2) (100 ng/2 microl, i.c.v.) with a subconvulsant dose of PTZ (20mg/kg, i.p.) caused seizures, further supporting a role for this prostaglandin in the convulsions induced by PTZ. Finally, we showed that the anticonvulsant action of celecoxib (2mg/kg, p.o.) was reversed by the intracerebroventricular administration of PGE(2) (10 ng/2 microl, i.c.v.). These data constitute strong converging pharmacological evidence supporting a facilitatory role for the COX-2/PGE(2) pathway in the seizures induced by PTZ," wrote M.S. Oliveira and colleagues, University Federal of Santa Maria.

The researchers concluded: "However, whether selective COX-2 inhibitors are safer anti-inflammatory drugs for epileptic patients than nonspecific inhibitors remains to be determined."

Oliveira and colleagues published their study in Epilepsy Research (Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures. Epilepsy Research, 2008;79(1):14-21).

For more information, contact M.S. Oliveira, Universidade Federal de Santa Maria, Departamento de Fisiologia e Farmacologia, Centro de Ciencias da Saude, 97105-900 Santa Maria, RS, Brazil.

Publisher contact information for the journal Epilepsy Research is: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands.

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