Effect of a major metabolite of the antiallergic drug repirinast on phosphodiesterase and adenylate cyclase activities.

MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid, CAS 63768-47-8), a major metabolite of the antiallergic drug repirinast (MY-5116, CAS 73080-51-0), inhibits antigen-induced histamine release from rat peritoneal mast cells. MY-1250 causes a rapid increase in cyclic adenosine monophosphate (AMP) levels in rat peritoneal mast cells. MY-1250 inhibited cyclic AMP phosphodiesterase activities from rat peritoneal cells and guinea pig lung tissue in a concentration dependent manner with IC50 values of 2000 mumol/l and 1670 mumol/l, respectively. However, MY-1250 showed no effect on adenylate cyclase activity from rat peritoneal cells. These results suggest that the inhibitory effect of MY-1250 on histamine release may be partly due to the inhibition of cyclic AMP phosphodiesterase activity.