Evidence of reduced uptake of convulsant in brain following prostaglandin E2

The toxic and convulsant effects of the acetylcholinesterase (AChE) inhibitor Soman, were examined in mice pretreated with various doses of prostaglandin E2 (PGE2), administered by either intraperitoneal injection (i.p.) or by intracerebroventricular (i.c.v.) infusion. PGE2 (i.p.) reduced the lethal effects of Soman slightly. PGE2 (i.p. and i.c.v.) delayed the onset and reduced the severity of cholinergically-induced convulsions, resulting from Soman. Whole brain AChE was measured at various times after Soman or Soman preceded by PGE2. PGE2 (i.p. or i.c.v.) reduced the rate at which Soman inhibited brain AChE, which appeared to be related to the increased time to onset of convulsive activity. Repeated injections of PGE2 did not delay convulsions indefinitely nor were convulsions terminated once they had started. The results suggest that the anticonvulsant properties of PGE2 may have been due, in part, to decreased cerebral circulation with subsequent reduction in the access of the convulsant to the brain and in part to direct neuronal effects.