The synthesis of prostaglandins and thromboxane in the mouse brain in vivo. Influence of drug induced convulsions, hypoxia and the anticonvulsants trimethadione and diazepam

Abstract

1. The i.v. administration of convulsant doses of penetrazole or picrotoxin induced an increase in PGF2 alpha, PGE2 and TXB2-like immunoreactive material in mouse brain tissue. The onset of increase coincided with the appearance of clonic seizures. 2. The anticonvulsant drugs trimethadione and diazepam reduced both convulsions and increase of the above arachidonic acid metabolites induced by pentetrazole or picrotoxin. 3. In synaptosomal preparations of the brain, neither pentetrazole (10(-3) mol 1(-1) picrotoxin (10(-4) mol 1(-1) nor trimethadione (5 x 10(-4) mol 1(-1)) had any influence on cyclooxygenase activity as indicated by the unimpaired PGF2 alpha-synthesis. 4. Under hypoxic conditions at equal durations as the seizures, the formation of PGF2 alpha and PGE2 was less than 10% of the amount occurring after penetrazole-induced convulsions. 5. It is concluded that the seizure-induced rise of PGF2 alpha, PGE2 and TXB2 is the result of increased central nervous activity.