Studies with Two New Phosphodiesterase Inhibitors (ICI 58,301 and ICI 63,197) on Anaphylaxis in Guinea Pigs, Mice and Rats

Abstract

Two compounds, ICI 58,301 (3-acetamido-6-methyl-8-<i>n</i>-propyl-s-triazolo[4,3-a]pyrazine) and ICI 63,197 (2-amino-6-methyl-5-oxo-4-<i>n</i>-propyl-4,5,-dihydro-s-triazolo[l,5-a]pyrimidine) facilitate the recovery of guinea pigs which have been subjected to anaphylactic shock. ICI 63,197 also reduces the amount of histamine released from the isolated lungs of sensitized guinea pigs after injection of antigen, partially inhibits passive cutaneous anaphylaxis in guinea pigs, protects mice from anaphylactic shock, and inhibits passive cutaneous anaphylaxis in rats sensitized with homologous reaginic or heterologous antisera. ICI 58,301 is not active in these conditions. Both compounds are potent inhibitors of 3′:5′-cyclic AMP phosphodiesterase and it is speculated that this property is associated with their anti-anaphylactic effects.